TW202508555A - Steroidal compounds, preparation methods and applications thereof - Google Patents

Abstract

The present invention discloses a steroid compound, a preparation method and application thereof. Specifically disclosed is a steroid compound having a structure as shown in Formula I, II or III or a pharmaceutically acceptable salt thereof. The compound of the present invention has SREBP pathway inhibitory activity and can be used to prevent and/or treat obesity, hyperlipidemia, fatty liver, diabetes, atherosclerosis, cardiovascular and cerebrovascular diseases, liver cancer, skin damage and other diseases.

Description

Steroidal compounds, preparation methods and applications thereof

This application claims priority to Chinese Patent Application No. 2023109336303 with a filing date of July 27, 2023, PCT Patent Application No. PCT/CN2023/109658 with a filing date of July 27, 2023, Chinese Patent Application No. 2024102813452 with a filing date of March 12, 2024, Chinese Patent Application No. 2024108909302 with a filing date of July 3, 2024, and Chinese Patent Application No. 202410983942X with a filing date of July 22, 2024. This application cites the full text of the above patent applications.

The present invention relates to a steroid compound, a preparation method and application thereof.

With the change of lifestyle, including the intake of high-calorie foods and high-sugar beverages, lack of exercise and physical activity, metabolic diseases represented by hyperlipidemia, obesity, type 2 diabetes and fatty liver have become increasingly serious health problems worldwide. Among them, fatty liver has become an important cause of chronic liver disease in Europe, America and wealthy areas of my country. The prevalence of simple liver lipid accumulation in ordinary adults is 10% to 30%, of which 10% to 20% is fatty hepatitis, and the latter has a 25% incidence of cirrhosis and liver cancer within 10 years. However, to date, the pathophysiological mechanism of fatty liver has not been fully elucidated, and there is still a lack of effective and specific therapeutic drugs in clinical practice. It is known that the accumulation of lipids such as cholesterol and triglycerides in the blood and liver is the main cause of hyperlipidemia, which is an important pathogenic factor for atherosclerosis, stroke and fatty liver disease. Therefore, the development of new drugs targeting lipid metabolism regulation pathways with the goal of reducing lipids is gradually becoming an important direction for the development of new metabolic disease drugs.

It is known that the lipid synthesis pathway of mammalian cells is an important factor in regulating lipid metabolic balance. The key factor regulating cholesterol and fatty acid synthesis is a type of transcription factor protein sterol response element binding protein SREBP (Sterol-Regulatory Element Binding Protein). The precursor of this type of protein is first synthesized in the endoplasmic reticulum (ER), and the precursor is transported to the Golgi apparatus through SREBP cleavage-activating protein (SCAP, SREBP cleavage-activating protein), and then cleaved by two proteases (Site-1protease (S1P) and Site-2protease (S2P)), releasing its N-terminal active domain, entering the cell nucleus to play the role of a transcription factor, binding to the SREBP response element (SRE) in the promoter region of the target gene, and activating the expression of downstream genes. The splicing and maturation of SREBP protein is strictly regulated by the level of intracellular sterols (such as cholesterol and 25-hydroxycholesterol). When cells accumulate sufficient cholesterol in the endoplasmic reticulum, cholesterol binds to SCAP and changes the conformation of SCAP, causing the SCAP-SREBP complex to bind to the protein Insig (Insulin-induced gene), thereby blocking the transport of SREBP to the Golgi apparatus and the subsequent activation of SREBP. Conversely, the active form of SREBP in the nucleus increases, promoting cellular lipid synthesis. In addition to cholesterol, 25-hydroxylcholesterol (25-HC) is another potent endogenous inhibitor of the SREBP pathway. Unlike cholesterol, which binds to SCAP, 25-HC directly binds to Insig and induces the binding of SCAP and Insig.

Previous studies have found that inhibiting the SREBP pathway is an effective strategy and method for preventing and/or treating metabolic diseases such as obesity, hyperlipidemia, fatty liver, atherosclerosis, diabetes, and cardiovascular and cerebrovascular diseases, skin damage, liver cancer and other diseases.

For hyperlipidemia, its pathogenesis is mainly caused by factors such as diet or gene mutation, which leads to increased lipid synthesis or abnormal lipid transport, resulting in excessive accumulation of lipids such as blood cholesterol and fatty acids. At present, statins and fibrates are the main lipid-lowering drugs in clinical practice. The mechanism of action of statins is to inhibit the cellular cholesterol synthesis pathway and promote the reverse transport of blood cholesterol. This shows that targeting the key factors of the cellular lipid synthesis pathway is an important means to effectively reduce lipid levels.

So far, there are no approved therapeutic drugs for fatty liver disease, so it is very important to identify therapeutic targets and develop new effective therapies. It is known that the pathogenesis of fatty liver disease involves multiple risk factors, such as the accumulation of triglycerides in the form of lipid droplets, which may cause steatosis, and abnormally increased cholesterol and fatty acids in cells, which can cause endoplasmic reticulum pressure and mitochondrial dysfunction, leading to cell death, inflammation and fibrosis. Among them, free cholesterol accumulation has been reported as a key driving factor in the transformation of simple steatosis to aggressive steatohepatitis. Secondly, a fatty liver mouse model was established. A simple high-fat diet without cholesterol can only induce steatosis even after long-term feeding, while adding 1-2% cholesterol to the diet is a necessary condition for achieving inflammation and fibrosis. Therefore, reducing cholesterol may become a new therapeutic strategy for fatty liver disease. Studies have shown that abnormal activation of SREBP was found in patients with fatty liver and fatty liver mouse models; the deletion or knockout of mouse liver-specific Scap can eliminate the activation of all SREBPs, thereby preventing the occurrence of fatty liver and hyperlipidemia. In addition, recent studies have shown that abnormal activation of SREBP induced by endoplasmic reticulum stress promotes lipogenesis and fatty liver. Therefore, these evidences suggest that lowering hepatic triglyceride and cholesterol levels by inhibiting the SREBP pathway is an effective strategy for preventing and/or treating metabolic disorders including fatty liver.

The technical problem to be solved by the present invention is to provide a new compound having inhibitory activity on the SREBP pathway.

The present invention provides a compound represented by formula I or a pharmaceutically acceptable salt thereof: wherein R ^4a is H; R ^4b is halogen, CN, -CH ₂ -CN, -CH ₂ -OH, -CH(CH ₃ )-OH, -COOH, -CH ₂ -COOH, C ₁ -C ₆ halogenated alkyl, -CH ₂ -OAc or NH ₂ ; or R ^4a and R ^4b and the carbon atoms to which they are connected together form or ; When there is a single bond between carbon atom No. 7 and carbon atom No. 8, R ^7a and R ^7b are independently H, halogen, CN, -CH ₂ -OH, -COOH, -CH ₂ -COOH, NH ₂ , C ₁ -C ₆ alkyl, C ₁ -C ₆ halogenated alkyl or -CH ₂ -CN; or, R ^7a and R ^7b and the carbon atoms to which they are connected together form , , or ; R ^8a is H; When there is a double bond between carbon atoms 7 and 8, R ^7a does not exist, R ^7b is a halogen; R ^8a does not exist; R ²¹ is , , , or ; n1 and n3 are independently 2, 3, 4 or 5; m1 and m3 are independently 0, 1, 2, 3, 4 or 5; Ring A and Ring C are independently C ₆ -C ₁₀ aryl, "a 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S" or C ₃ -C ₆ cycloalkyl; ^RA and ^RC are independently halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ halogenated alkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ halogenated alkoxy; R ¹ is or NR ^1a R ^1b ; R ^1a and R ^1b are independently H or C ₁ -C ₆ alkyl; A carbon atom with "*" indicates that when it is a chiral carbon atom, it is in R configuration, S configuration or a mixture of the two; A carbon atom with "#" indicates that when it is a chiral carbon atom, it is in R configuration, S configuration or a mixture of the two; A carbon atom with "&" indicates that when it is a chiral carbon atom, it is independently in R configuration, S configuration or a mixture of the two; The compound shown in formula I is not the following compound: , and , and its isomers.

In certain preferred embodiments of the present invention, certain groups in the compound or its pharmaceutically acceptable salt are defined as follows, and the unmentioned groups are the same as those described in any embodiment of the present invention (referred to as "in some embodiments" for short), in R ^4b , the halogen is independently F, Cl, Br or I; for example, Br.

In some embodiments, in R ^4b , the C ₁ -C ₆ halogenated alkyl group is independently CHF ₂ , CH ₂ F or CF ₃ .

In some embodiments, in R ^7a and R ^7b , the halogen is independently F, Cl, Br or I; preferably F.

In some embodiments, in R ^7a and R ^7b , the C ₁ -C ₆ alkyl group is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

In some embodiments, in R ^7a and R ^7b , the C ₁ -C ₆ halogenated alkyl group is independently CHF ₂ , CH ₂ F or CF ₃ , for example CHF ₂ .

In some embodiments, in Ring A and Ring C, the C ₆ -C ₁₀ aryl group is independently phenyl or naphthyl, preferably phenyl.

In some embodiments, in Ring A and Ring C, the “heteroatoms selected from 1, 2 or 3 of N, O and S, 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms” are independently “heteroatoms selected from 1, 2 or 3 of N, O and S, 5-6 membered or 9-10 membered heteroaryl group having 1 or 2 heteroatoms”, for example, pyridyl (e.g. , or ).

In some embodiments, in Ring A and Ring C, the C ₃ -C ₆ cycloalkyl group is independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

In some embodiments, in ^RA and ^RC , the halogen is independently F, Cl, Br or I; preferably F or Cl, such as F.

In some embodiments, in ^RA and ^RC , the C ₁ -C ₆ alkyl group is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

In some embodiments, in ^RA and ^RC , the C ₁ -C ₆ halogenated alkyl group is independently CHF ₂ , CH ₂ F or CF ₃ .

In some embodiments, in ^RA and ^RC , the C ₁ -C ₆ alkoxy group is independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, preferably methoxy or ethoxy.

In some embodiments, in ^RA and ^RC , the C ₁ -C ₆ halogenated alkoxy group is independently -OCHF ₂ , -OCH ₂ F or -OCF ₃ ; preferably -OCF ₃ .

In some embodiments, in R ^1a and R ^1b , the C ₁ -C ₆ alkyl group is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, such as methyl.

In some embodiments, in Formula I, a carbon atom with a "*" indicates that when it is a chiral carbon atom, it is in the S configuration.

In some embodiments, in Formula I, for , or .

In some embodiments, R ^4a is H; R ^4b is halogen (e.g., Br), CN, -CH ₂ -CN, -CH ₂ -OH, -CH(CH ₃ )-OH, -COOH, -CH ₂ -COOH, -CH ₂ -OAc, or NH ₂ ; or, R ^4a and R ^4b together with the carbon atoms to which they are attached form or For example, R ^4a is H; R ^4b is Br, CN, -CH ₂ -CN, -CH ₂ -OH, -CH(CH ₃ )-OH, -COOH, -CH ₂ -OAc or NH ₂ ; or, R ^4a and R ^4b together with the carbon atoms to which they are connected form .

In some embodiments, when there is a single bond between carbon atom No. 7 and carbon atom No. 8, R ^7a and R ^7b are independently H or halogen (e.g., F), preferably, R ^7a and R ^7b are both H or halogen (e.g., F); when there is a double bond between carbon atom No. 7 and carbon atom No. 8, R ^7a does not exist, R ^7b is halogen (e.g., F); R ^8a does not exist.

In some embodiments, R ²¹ is , or ,For example .

In some embodiments, Ring A and Ring C are independently C ₆ -C ₁₀ aryl or "a 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S, and having 1, 2 or 3 heteroatoms".

In some embodiments, ^RA and ^RC are independently halogen, C ₁ -C ₆ alkoxy, or C ₁ -C ₆ halogenated alkoxy.

In some embodiments, n1 is 3.

In some embodiments, n3 is 3.

In some embodiments, m1 is 0, 1, 2 or 3.

In some embodiments, m3 is 0, 1, 2 or 3.

In some implementations, for , , , , , , , , , , , , or .

In some implementations, for , , , , , , or .

In some implementations, for , , , , , , , , , , , , , , , , , or .

In some embodiments, R ²¹ is , , , , , , , , , , , , , , , , , , , , , or .

The present invention also provides a compound represented by formula II or a pharmaceutically acceptable salt thereof: wherein R ^4c is H; R ^4d is H or OH; R ^7c is H, and R ^7d is independently CN, -CH ₂ -OH, -COOH, C ₁ -C ₆ alkyl, C ₁ -C ₆ halogenated alkyl, -CH ₂ -COOH, NH ₂ , -CH ₂ -CN or Cl; or, R ^7c and R ^7d and the carbon atoms to which they are connected together form , , or ; R ²² is , , or ; n2 is 2, 3, 4 or 5; m2 is 0, 1, 2, 3, 4 or 5; Ring B is C ₆ -C ₁₀ aryl, "a 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S" or C ₃ -C ₆ cycloalkyl; ^RB is independently halogen, C ₁ -C ₆ alkyl, C 1 -C ₆ halogenated alkyl, C _{1 -C 6} alkoxy or C ₁ -C ₆ halogenated alkoxy; A carbon atom with "*" indicates that it is in R configuration, S configuration or a mixture of the two when it is a chiral carbon atom; A carbon atom with "#" indicates that it is in R configuration, S configuration or a mixture of the two when it is a chiral carbon atom; The carbon atom with "&" indicates that when it is a chiral carbon atom, it is in R configuration, S configuration or a mixture of the two; The compound shown in formula II is not the following compound: and its isomers.

In some embodiments, in R ^7c and R ^7d , the C ₁ -C ₆ alkyl group is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

In some embodiments, in R ^7c and R ^7d , the C ₁ -C ₆ halogenated alkyl group is independently CHF ₂ , CH ₂ F or CF ₃ , for example CHF ₂ .

In some embodiments, in ring B, the C ₆ -C ₁₀ aryl group is phenyl or naphthyl, preferably phenyl.

In some embodiments, in ring B, the “heteroatoms selected from 1, 2 or 3 of N, O and S, 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms” is “heteroatoms selected from 1, 2 or 3 of N, O and S, 5-6 membered or 9-10 membered heteroaryl group having 1 or 2 heteroatoms”, for example, pyridyl (e.g. , or ).

In some embodiments, in ring B, the C ₃ -C ₆ cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

In some embodiments, in ^RB , the halogen is independently F, Cl, Br or I; preferably F or Cl, such as F.

In some embodiments, in ^RB , the _C1 - _C6 alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

In some embodiments, in ^RB , the C ₁ -C ₆ halogenated alkyl group is independently CHF ₂ , CH ₂ F or CF ₃ .

In some embodiments, in ^RB , the C ₁ -C ₆ alkoxy group is independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, preferably methoxy or ethoxy.

In some embodiments, in ^RB , the C ₁ -C ₆ halogenated alkoxy group is independently -OCHF ₂ , -OCH ₂ F or -OCF ₃ ; preferably -OCF ₃ .

In some embodiments, in Formula II, the carbon atom with "*" indicates that when it is a chiral carbon atom, it is in S configuration.

In some embodiments, in Formula II, a carbon atom with a "#" indicates that when it is a chiral carbon atom, it is in the R configuration.

In some embodiments, in Formula II, for or .

In some embodiments, R ^7c is H, R ^7d is independently CN, -CH ₃ , -CH ₂ -OH, -COOH, -CHF ₂ , -CH ₂ -COOH, NH ₂ , -CH ₂ -CN or Cl; or, R ^7c and R ^7d together with the carbon atom to which they are attached form , , or ; For example, R ^7c is H, R ^7d is independently CN, -CH ₂ -OH, -CH ₃ , NH ₂ , -CH ₂ -CN, -CF ₂ H, -COOH, or R ^7c and R ^7d and the carbon atoms to which they are connected together form or .

In some embodiments, ^R22 is , or .

In some embodiments, Ring B is a C ₆ -C ₁₀ aryl group or a "5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S, and having 1, 2 or 3 heteroatoms".

In some embodiments, ^RB is independently halogen, _C1 - _C6 alkoxy, or _C1 - _C6 halogenated alkoxy.

In some embodiments, n2 is 3.

In some embodiments, m2 is 0, 1, 2 or 3.

In some implementations, for , , , , , , , , , , , , , , , , , , or .

In some embodiments, ^R22 is , , , , , , , , , , , , , , , , , , , , , or .

In some embodiments, in Formula II, for , , , , , , , , , , , , , , , , or .

The present invention also provides a compound represented by formula III or a pharmaceutically acceptable salt thereof: wherein, R ^3a is H or C ₁ -C ₆ alkyl; R ^3b is -O-(CH ₂ )nR ^3-1 , NR ^3-2 R ^3-3 or OH; when R ^3b is OH, R ^3a is C ₁ -C ₆ alkyl; n is 1, 2, 3 or 4; R ^3-1 is OH or -C(O)OR ^3-1a ; R ^3-1a is H or C ₁ -C ₆ alkyl; R ^3-2 and R ^3-3 are independently H or -S(O) ₂ R ^3-2a ; R ^3-2a is C ₁ -C ₆ halogenated alkyl or C ₁ -C ₆ alkyl; R ^4e is H; R ^4f is H, OH or -O-(CH ₂ )mOR ^4-1 ; or R ^4e and R ^4f and the carbon atoms to which they are connected together form ; m is 1 or 2; R ^4-1 is C ₁ -C ₆ alkyl; A carbon atom with "*" indicates that when it is a chiral carbon atom, it is in R configuration, S configuration or a mixture of the two; A carbon atom with "#" indicates that when it is a chiral carbon atom, it is in R configuration, S configuration or a mixture of the two; The compound represented by formula III is not the following compound: and , and its isomers.

In some embodiments, in R ^3a , the C ₁ -C ₆ alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, such as methyl.

In some embodiments, in R ^3-1a , the C ₁ -C ₆ alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example tert-butyl.

In some embodiments, in R ^3-2a , the C ₁ -C ₆ halogenated alkyl group is CHF ₂ , CH ₂ F or CF ₃ , such as CF ₃ .

In some embodiments, in R ^4-1 , the C ₁ -C ₆ alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, such as ethyl.

In some embodiments, in Formula III, for , , , , , or .

In some embodiments, n is 1, 2 or 3.

In some embodiments, R ^3-2 is H and R ^3-3 is -S(O) ₂ R ^3-2a .

In some embodiments, m is 1.

In some embodiments, R ^3a is H, R ^3b is , 、-NH ₂ 、 , , , ; or, R ^3a is methyl and R ^3b is OH.

In some embodiments, R ^4e is H; R ^4f is H, OH or ; or R ^4e and R ^4f together with the carbon atoms to which they are attached form .

In some embodiments, in Formula III, for , , , , , , , , , , or .

The present invention also provides any of the following compounds or pharmaceutically acceptable salts thereof: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or .

The present invention also provides a pharmaceutical composition comprising the compound described in any one of the present invention or a pharmaceutically acceptable salt thereof, and at least one pharmaceutical excipient.

The present invention also provides a use of a compound as described in any one of the present invention or a pharmaceutically acceptable salt thereof or a pharmaceutical composition as described in any one of the present invention in the preparation of a drug for preventing and/or treating a disease, wherein the disease is obesity, hyperlipidemia, fatty liver, diabetes, atherosclerosis, cardiovascular and cerebrovascular diseases, liver cancer or skin damage.

The present invention also provides a use of a compound as described in any one of the present invention or a pharmaceutically acceptable salt thereof or a pharmaceutical composition as described above in the preparation of a drug for inhibiting the SREBP pathway.

The present invention also provides a method for inhibiting SREBP pathway, which comprises administering an effective amount of the compound as described above or a pharmaceutically acceptable salt thereof to a subject.

The present invention also provides a method for preventing and/or treating a disease, comprising administering to a subject an effective amount of a compound as described in any one of the present invention or a pharmaceutically acceptable salt thereof, wherein the disease is obesity, hyperlipidemia, fatty liver, diabetes, atherosclerosis, cardiovascular and cerebrovascular diseases, liver cancer or skin damage. Definition and Description

Unless otherwise specified, the following terms and phrases used herein are intended to have the following meanings. A particular term or phrase should not be considered ambiguous or unclear in the absence of a specific definition, but should be understood according to its ordinary meaning. When a trade name appears in this article, it is intended to refer to the corresponding trade name or its active ingredient.

As used herein, the term "substituted" or "substituent" refers to the replacement of a hydrogen atom in a group by a specified group. When the position of substitution is not specified, substitution can be at any position, but is permitted only if a stable or chemically feasible compound is formed. Examples are as follows: The structure represents that the hydrogen atom on ring A is replaced by m1 ^RAs . When multiple ^RAs are present, each ^RA may be the same or different.

When any variable (eg, ^RA ) occurs more than once in a compound's composition or structure, its definition on each occurrence is independent.

As used herein, the term "alkyl" refers to a saturated linear or branched monovalent hydrocarbon group. _C1 - _C6 alkyl refers to an alkyl group having 1 to 6 carbon atoms. In some embodiments, _C1 - _C6 alkyl may be _C1 - _C4 alkyl. _C1 - _C4 alkyl includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl.

As used herein, the term "haloalkyl" refers to a group formed by replacing one or more hydrogen atoms in an alkyl group with a halogen, wherein the definition of alkyl is as described above. Examples of halogenated alkyl groups include, but are not limited to, monofluoromethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, and the like.

In this document, the term "alkoxy" refers to -O-alkyl, wherein alkyl is as defined above. _{C 1} -C ₄ alkoxy refers to -O-(C ₁ -C ₄ alkyl), wherein C ₁ -C ₄ alkyl is as defined above, that is, C ₁ -C ₄ alkoxy can be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy.

As used herein, the term "cycloalkyl" refers to a saturated monocyclic or polycyclic (eg, cyclo, spiro, or bridged) cyclic hydrocarbon group. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, The C _3-6 cycloalkyl group may specifically be C ₃ , C ₄ , C ₅ , or C ₆ cycloalkyl group. In some embodiments, the cycloalkyl group is monocyclic. In some embodiments, the cycloalkyl group is polycyclic (e.g., cyclic, spirocyclic, or bridged).

Herein, the term "C _6-10 aryl group" refers to a phenyl group or a naphthyl group.

In this article, the term "heteroaryl" refers to an aromatic monocyclic or fused ring group formed by a carbon atom and at least one heteroatom, wherein the heteroatom is independently selected from 1, 2 or 3 of N, O and S. The 5-10 membered heteroaryl can be specifically a 5-, 6-, 7-, 8-, 9- or 10-membered heteroaryl, such as a 5-6 membered heteroaryl or an 8-10 membered fused heteroaryl. The 5-6 membered heteroaryl is monocyclic, and specific examples include but are not limited to pyrrole, furan, thiophene, oxazole, isoxazole, thiazole, isothiazole, pyrazole, imidazole, pyridine, pyrimidine, pyrazine. Examples of 8-10 membered fused aryl groups include, but are not limited to, benzopyrrole, benzofuran, benzothiophene, benzoxazole, benzoisoxazole, benzothiazole, benzoisothiazole, benzopyrazole, benzimidazole, benzopyridine, benzopyrimidine, benzopyrazine, thiazolothiazole, pyridopyridine, pyridopyrazine, pyridopyrimidine, .

In this article, the chemical structure Indicates the connection position. Contained in a ring group and not specified When the ring atoms are connected, Attachment to any ring atom is possible, but is permitted only if it results in a stable or chemically viable compound.

As used herein, the term "pharmaceutically acceptable salt" refers to a salt formed by a suitable non-toxic organic acid, inorganic acid, organic base or inorganic base and a compound, which retains the biological activity of the compound. The organic acid may be any conventional organic acid capable of forming a salt in the art. The inorganic acid may be any conventional inorganic acid capable of forming a salt in the art. The organic base may be any conventional organic base capable of forming a salt in the art. The inorganic base may be any conventional inorganic base capable of forming a salt in the art.

In chemical structures, solid wedge-shaped bonds ( ) and the Dashed Wedge Key ( ) represents the absolute configuration of a stereocenter, with a straight solid line key ( ) and the straight dash key ( ) represents the relative configuration of the stereocenter. " does not specify the configuration, that is, if there are configurational isomers in the chemical structure, the bond" "Can be" "or" ", or both "and" "Two configurations (for example, " "and" When the specific configuration of a carbon-carbon double bond is not specified, it can be in E or Z configuration. Stereoisomers can be synthesized using chiral starting materials, prepared by chiral resolution, or can be separated using conventional techniques such as, but not limited to, high performance liquid chromatography (HPLC) using a chiral column.

As used herein, the term "subject" includes any animal, preferably a mammal, more preferably a human.

In this article, the term "effective amount" refers to a sufficient amount of a drug or pharmaceutical agent that is non-toxic but can achieve the desired effect. The determination of the effective amount varies from person to person, depending on the age and general condition of the recipient, and also on the specific active substance. The appropriate effective amount in each case can be determined by a person skilled in the art according to routine experiments.

Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

The reagents and raw materials used in the present invention are commercially available.

The positive and progressive effect of the present invention is that the present invention provides a new class of compounds which have inhibitory activity on the SREBP pathway and can be used to prevent and/or treat diseases such as obesity, hyperlipidemia, fatty liver, diabetes, atherosclerosis, cardiovascular and cerebrovascular diseases, liver cancer, and skin damage.

The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods without specific conditions in the following examples are carried out according to conventional methods and conditions, or selected according to the product instructions. Preparation of Key Intermediates Examples I & II Intermediate I (5R)-5-[(3aS,5aR,5bS,7aR,8R,10aS,10bS, 12aR,12bR)-11,11 -difluoro -2,2,5a,7a -tetramethyl -4,5,5a,5b,6,7,7a, 8,9,10,10a,10b,11,12,12a,12b- hexahydro -3aH- cyclopenta [1',2':1,2] phenanthro [7,8-d][1,3] dioxacyclopenta -8- yl ] hexanal I Intermediate II (5R)-5-[(3aS,5aR,5bR,7aR,8R,10aR,12aR, Preparation of 11- fluoro- 2,2,5a,7a -tetramethyl -4,5,5a,5b,6,7,7a,8,9, 10,10a,12,12a,12b- tetradecahydro -3aH-cyclopenta [ 1',2':7,8] phenanthro [1,2-d][1,3] dioxacyclopenta [8- yl ] hexanal II

Step 1: Dissolve (22E,24S)-stigmaster-6(5),22(23)-diene-3β-ol I-1 (5.00 g, 12.11 mmol, 1.0 eq) in dichloromethane (50 mL). Place the reaction system in an ice-water bath and cool to about 5 ^° C. Add acetic anhydride (3.4 mL, 36.35 mmol, 3.0 eq), 4-dimethylaminopyridine (300 mg, 2.42 mmol, 0.2 eq) and triethylamine (8 mL, 60.57 mmol, 5.0 eq) to the reaction system in sequence. Stir the reaction system at room temperature for 2 hours. After the reaction was complete as monitored by TLC (petroleum ether: ethyl acetate = 10:1), the reaction solution was quenched with methanol (20 mL), washed once with saturated sodium bicarbonate (~50 mL) and water (~50 mL), dried over anhydrous sodium sulfate, concentrated, and when the solution was almost dry, methanol (~20 mL) was added. The mixture was stirred in an ice bath for 30 min, filtered, and the filter cake was rinsed with a small amount of methanol. The filter cake was dried to obtain white solid acetic acid-(1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2R,3E,5S)-5-ethyl-6-methylhept-3-en-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b, 10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester I-2 (5.30 g, purity 90.0 %, yield 86.58%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.37 (d, J = 4.8 Hz, 1H), 5.09 (ddd, J = 56.1, 15.2, 8.6 Hz, 2H), 4.61 (ddd, J = 15.9, 9.0, 4.2 Hz, 1H), 2.32 (d, J = 7.3 Hz, 2H), 2.03 (s, 3H), 2.01 – 1.92 (m, 2H), 1.87 (dd, J = 8.9, 6.6 Hz, 2H), 1.73 – 1.40 (m, 12H), 1.30 – 1.07 (m, 6H), 1.02 (t, J = 3.3 Hz, 6H), 0.87 – 0.79 (m, 9H), 0.70 (s, 3H).

Step 2: Weigh (1R,3aS,3bS,7S, 9aR,9bS,11aR)-1-[(2R,3E,5S)-5-ethyl-6-methylhept-3-en-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a, 9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate I-2 (10.0 g, 22 mmol, 1 eq) and dissolve it in tetrahydrofuran (200 mL) and water (20.0 mL). Add pyridine (4.5 mL, 55 mmol, 2.5 eq), N-methylphenoxylate (10.30 g, 88 mmol, 4 eq) at room temperature. Potassium pyrophosphate (0.81 g, 2.2 mmol, 0.1 eq), stirred at room temperature overnight, monitored by TLC (petroleum ether: ethyl acetate = 3:1), some of the starting materials remained, and an intermediate (ortho-diol was generated), then sodium periodate (18.80 g, 88 mmol, 4 eq) was added to the reaction solution at 0°C, stirred at room temperature for 1 hour, and detected by TLC (petroleum ether: ethyl acetate = 3:1), some of the starting materials remained, and the intermediate was converted into the product. Then, 50 mL of water and 50 mL of ethyl acetate were added for extraction, dried, concentrated, and the crude product was purified by column chromatography (petroleum ether: ethyl acetate = 60:1) to obtain acetic acid-(1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-1-[(2R, 3E, 5S)-5-ethyl-6-methylhept-3-en-2-yl]-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester I-3 (3.3 g, purity 60 %, yield 19.8%) white solid acetate-(1R,3aS,3bS,7S,9aR,9bS,11aS)-1-[(1S)-1-methylylethyl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester (1.9 g, purity 90.0 %, yield 21.20%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.50 (d, J = 3.3 Hz, 1H), 5.31 (d, J = 5.1 Hz, 1H), 4.54 (dd, J = 6.4, 4.2 Hz, 1H), 2.34 – 2.23 (m, 3H), 1.96 (s, 3H), 1.89 (dt, J = 6.6, 3.6 Hz, 2H), 1.83 – 1.72 (m, 3H), 1.66 – 1.09 (m, 14H), 1.06 (d, J = 6.8 Hz, 3H), 0.96 (s, 3H), 0.66 (s, 3H).

Step 3: (Methoxymethyl)triphenylphosphonium chloride (55.21 g, 161.052 mmol, 5.0 eq) was dissolved in anhydrous tetrahydrofuran (100 mL). The system was cooled to -10 ^° C in a dry ice ethyl acetate bath. Sodium bis(trimethylsilyl)amide (80.526 mL, 1 mol/L, 2.5 eq), stirred in a dry ice ethyl acetate bath for 30 minutes, acetic acid-(1R,3aS,3bS,7S,9aR,9bS,11aS)-1-[(1S)-1-methylethyl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester I-3 (12.0 g, 13.4 mmol, 1.0 eq) was dissolved in anhydrous tetrahydrofuran (50 mL) and added to the reaction solution, the system was returned to room temperature and stirred for 30 minutes. TLC (petroleum ether: ethyl acetate = 10:1) monitored the reaction to be complete. 100 mL of saturated sodium bicarbonate solution was slowly added to the reaction system, extracted with ethyl acetate (100 mL×3), the organic phase was collected and washed with water (100 mL×2), washed with saturated brine, dried over anhydrous sodium sulfate, and the organic phase was concentrated to obtain yellow solid acetic acid-(1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2S,3E)-4-methoxybut-3-en-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester I-4 (8 g, purity 90.0 %, yield 65.0 %), and the crude product was directly used for the next reaction.

Step 4: Acetic acid-(1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2S,3E)-4-methoxybut-3-en-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester I-4 (8 g, 12.5 mmol, 1.0 eq ) was dissolved in tetrahydrofuran (100 mL), and dilute hydrochloric acid (5 mol/L, 50 mL) was slowly added, and the reaction mixture was stirred at room temperature for 30 minutes. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 10:1). After the reaction was complete, 80 mL of water was added to the reaction, and the reaction solution was extracted with ethyl acetate (50 mL×3), washed with saturated brine (20 mL×3), dried over anhydrous sulfuric acid, and the organic phase was collected and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 50:1 to 30:1 to 4:1) and concentrated to obtain white solid acetic acid-(1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2R)-1-methylpropan-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester I-5 (6.3 g, purity 90%, yield 48.63%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.76 (dd, J = 3.3, 1.3 Hz, 1H), 5.37 (d, J = 4.9 Hz, 1H), 4.65 – 4.55 (m, 1H), 2.46 (dd, J = 15.6, 2.8 Hz, 1H), 2.32 (d, J = 7.0 Hz, 2H), 2.22 – 2.14 (m, 1H), 2.03 (s, 3H), 2.03 – 1.93 (m, 2H), 1.89 – 1.78 (m, 3H), 1.66 – 1.40 (m, 9H), 1.17 (dddd, J = 16.5, 14.2, 10.9, 7.1 Hz, 6H), 1.03 (dd, J = 7.5, 3.5 Hz, 6H), 0.73 (d, J = 5.3 Hz, 3H).

Step 5: ( The reactant acetic acid-(1R,3aS,3bS,7S, 9aR,9bS,11aR)-1-[(2R)-1-methylpropan-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester I-5 (10.00 g, 25.87 mmol, 1.0 eq) was dissolved in anhydrous tetrahydrofuran (150 mL), (triphenyl-λ5-methylphosphinoylidene) methyl acetate (51.89 g, 155.21 mmol, 6.0 eq) was added, and the reaction system was stirred at 90 ^° C for 18 h. The reaction raw materials were consumed by NMR. 100 mL of water was added to the reaction system, extracted with ethyl acetate (100 mL×3), the organic phase was collected and washed with water (100 mL×2), washed with saturated brine, dried with anhydrous sodium sulfate, and the organic phase was collected and concentrated to obtain a crude product. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 60:1 to 30:1) to obtain white solid (2E,5R)-5-[(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hex-2-enoic acid methyl ester I-6 (9.0 g, purity 90%, yield 71.1%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.95 (ddd, J = 15.4, 8.7, 6.4 Hz, 1H), 6.26 (d, J = 11.6 Hz, 0H), 5.82 (d, J = 15.5 Hz, 1H), 5.37 (d, J = 4.9 Hz, 1H), 4.60 (tdd, J = 10.9, 6.6, 4.2 Hz, 1H), 3.72 (d, J = 10.2 Hz, 3H), 2.35 – 2.24 (m, 3H), 2.03 (s, 3H), 2.01 – 1.91 (m, 3H), 1.90 – 1.78 (m, 3H), 1.68 – 1.40 (m, 8H), 1.31 – 1.07 (m, 5H), 1.02 (s, 3H), 0.95 (d, J = 6.7 Hz, 3H), 0.72 – 0.68 (m, 3H).

Step 6: The reactant (2E,5R)-5-[(1R,3aS,3bS,7S, 9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hex-2-enoic acid methyl ester I-6 (10 g, 22.59 mmol, 1.0 eq) was dissolved in a mixed solvent of tetrahydrofuran (100 mL) and methanol (50 mL), nickel chloride (2.93 g, 22.59 mmol, 1.0 eq) was added, and sodium borohydride (1.28 g, 33.89 mmol), the reaction system was stirred at room temperature for 1 h. According to NMR monitoring, the reaction raw materials were consumed. 100 mL of water was added to the reaction system, extracted with ethyl acetate (100 mL×3), the organic phase was collected and washed with water (100 mL×2), washed with saturated brine, dried with anhydrous sodium sulfate, and the organic phase was collected and concentrated to obtain a crude product. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 60:1 to 30:1) to obtain white solid (5R)-5-[(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthren-1-yl]hexanoic acid methyl ester I-7 (9 g, purity 90%, yield 80.6%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.37 (d, J = 4.9 Hz, 1H), 4.66 – 4.54 (m, 1H), 3.67 (s, 3H), 2.29 (ddd, J = 15.9, 11.9, 6.6 Hz, 4H), 2.03 (s, 3H), 2.02 – 1.93 (m, 2H), 1.82 (ddd, J = 13.0, 10.8, 8.3 Hz, 3H), 1.62 – 1.38 (m, 11H), 1.19 (dddd, J = 32.6, 25.0, 13.7, 6.9 Hz, 9H), 1.01 (d, J = 5.8 Hz, 3H), 0.93 (d, J = 6.6 Hz, 3H), 0.87 (tdd, J = 10.2, 4.8, 2.0 Hz, 4H), 0.67 (s, 3H).

Step 7: In a 250 mL round-bottom flask at room temperature, (5R)-5-[(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthren-1-yl]hexanoic acid methyl ester I-7 (2.5 g, 5.62 mmol) was dissolved in chloroform (80 mL), N-methylmorpholine (1.71 g, 16.87 mmol) and selenium dioxide (1.56 g, 14.06 mmol) were added at room temperature, followed by stirring at 70°C for 18 hours. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 10:1). After the reaction was completed, the mixture was quenched with water (100 mL), extracted with dichloromethane (80 mL×3), the organic phase was washed with saturated brine (150 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) to obtain a white solid (5R)-5-[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-7-acetyloxy-6-hydroxy-9a, 11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-8 (1.4 g, purity: 90%, yield: 48.65%). ¹ H NMR (400 MHz, CDCl ₃ ) δ = 5.75 – 5.65 (m, 1H), 4.80 – 4.65 (m, 1H), 4.25 (d, J =2.6, 1H), 3.67 (s, 3H), 2.33 – 2.22 (m, 2H), 2.10 (s, 3H), 2.07 – 1.98 (m, 2H), 1.92 – 1.36 (m, 17H), 1.22 (s, 3H), 1.19 – 1.06 (m, 5H), 0.93 (d, J =6.6, 3H), 0.68 (s, 3H).

Step 8: The reactant (5R)-5-[(1R,3aS,3bS,6R,7S, 9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-8 (5 g, 1.0 eq) was dissolved in methanol (150 mL), potassium carbonate (6.37 g, 46 mmol, 4.0 eq) was added, and the reaction system was stirred at room temperature for 30 min. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 5:1). The reaction was stopped when the starting material was consumed. Water (100 mL) was added to the reaction system, and the aqueous layer was extracted with ethyl acetate (3×50 mL). The ethyl acetate layers were combined and washed with saturated brine (3×50 mL). The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and concentrated to obtain the crude product (5R)-5-[(1R,3aS,3bS,6R,7S,9aR,9bS,11aR)-6,7-dihydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-9 , which was directly used in the next reaction.

Step 9: The reactant (5R)-5-[(1R,3aS,3bS,6R,7S, 9aR,9bS,11aR)-6,7-dihydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6, 7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-9 (5 g, 11.9 mmol, 1 eq) was dissolved in acetone (150 mL), p-toluenesulfonic acid (1.59 g, 8.4 mmol, 0.7 eq) and 4A molecular sieve were added, and the reaction system was stirred at room temperature for 1 h. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 10:1). After the raw material was consumed, the reaction was stopped by quenching with saturated sodium sulfite. 100 mL of water was added to the reaction system, and ethyl acetate (50 mL×3) was used for extraction. The organic phase was collected and dried with anhydrous sodium sulfate. The organic phase was dried by vacuum rotary drying to obtain a crude product. The crude product was dissolved in ethyl acetate and purified by column chromatography (petroleum ether:ethyl acetate = 95:5) to give white solid (5R)-5-[(3aR,3R,5aS,9aS,9bS)-7-[(4R)-2,2-dimethyl-1,3-dioxacyclopentan-4-yl]-3a,6,6-trimethyl-2,3,3a,4,5,5a,6,9,9a,9b-decahydro-1H-cyclopenta[1,2-a]naphthalen-3-yl]hexanoic acid methyl ester I-10 (3.8 g, purity 90%, yield 62%). 1H NMR (400 MHz, CDCl3) δ 5.80 (d, J = 2.9 Hz, 1H), 4.41 (d, J = 5.8 Hz, 1H), 4.10 (dd, J = 13.5, 6.5 Hz, 1H), 3.67 (s, 3H), 2.35 – 2.20 (m, 2H), 2.14 – 1.98 (m, 2H), 1.87 – 1.56 (m, 10H), 1.53 (s, 3H), 1.45 – 1.37 (m, 3H), 1.35 (s, 3H), 1.28 – 1.21 (m, 1H), 1.16 (s, 3H), 1.14 – 0.97 (m, 6H), 0.93 (d, J = 6.5 Hz, 3H), 0.69 (s, 3H).

Step 10: Dissolve compound (5R)-5-[(3aR,3R,5aS,9aS,9bS)-7-[(4R)-2,2-dimethyl-1,3-dioxacyclopentan-4-yl]-3a,6,6-trimethyl-2,3,3a,4,5,5a,6,9,9a,9b-decahydro-1H-cyclopenta[1,2-a]naphthalen-3-yl]hexanoic acid methyl ester I-10 (3.8 g, 8.2 mmol, 1.0 eq) in acetone (50 mL), add N-hydroxyphthalimide (0.54 g, 3.3 mmol, 0.8 eq), tert-butyl hydroperoxide (12 mL, 66 mmol, 8.0 eq) and anhydrous cobalt(II) acetate. (0.29 g, 1.6 mmol, 0.2 eq), the resulting mixture was stirred in the reaction solution under N ₂ at 25°C for 18 hours. TLC (petroleum ether: ethyl acetate = 10:1) monitored the reaction. The raw material was basically consumed, quenched with saturated sodium sulfite, water (10 mL) was added to the reaction system, and the aqueous layer was extracted with ethyl acetate (3×15 mL). The organic layers were combined and washed with saturated brine (15 mL), dried over anhydrous sodium sulfate, filtered and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 87: 13) to give white solid (5R)-5-[(3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12bR)-2,2,5a,7a-tetramethyl-11-oxyylidene-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]hexanoic acid methyl ester I-11 (2.5 g, purity 95%. Yield 60%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.85 (s, 1H), 4.45 (d, J = 6.4 Hz, 1H), 4.26 (dd, J = 11.3, 5.5 Hz, 1H), 3.60 (s, 3H), 2.34 – 2.25 (m, 2H), 1.86 – 1.70 (m, 2H), 1.58 (dddd, J = 16.6, 11.8, 6.3, 2.3 Hz, 5H), 1.50 (s, 3H), 1.40 (dddd, J = 16.5, 9.3, 3.9 Hz, 4H), 1.30 (s, 3H), 1.26 (s, 4H), 1.12 – 0.97 (m, 4H), 0.87 (d, J = 6.6 Hz, 3H), 0.66 – 0.59 (m, 3H).

Step 11: Compound (5R)-5-[(1R,3aS,3bS,6R,7S, 9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-11 (2.4 g, 5.1 mmol, 1.0 eq) was dissolved in methanol (100 mL) and ethyl acetate (50 mL), and then palladium carbon (1.2 g, 11 mmol, 2.2 eq) was added and the reaction system was replaced with hydrogen atmosphere. The reaction system was stirred at room temperature for 1 h. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 5:1), and the starting material was completely consumed. The reaction system was filtered, and the organic phase was collected and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 90: 10) to give white solid (5R)-5-[(3aS,5aR,5bS,7aR,8R,10aS,10bS, 12aR,12bR)-2,2,5a,7a-tetramethyl-11-oxyylidene-4,5,5a,5b,6,7,7a,8,9,10,10a,10b, 11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]hexanoic acid methyl ester I-12 (1.7 g, purity 95%, yield 67%). 1H NMR (400 MHz, CDCl3) δ 4.00 – 3.87 (m, 2H), 3.60 (s, 3H), 2.75 – 2.66 (m, 1H), 2.36 (t, J = 11.3 Hz, 1H), 2.25 – 2.09 (m, 4H), 1.85 (dddd, J = 28.9, 13.2, 6.5, 3.1 Hz, 3H), 1.62 (dddd, J = 20.4, 14.3, 6.7, 3.3 Hz, 4H), 1.46 (s, 3H), 1.43 – 1.26 (m, 5H), 1.23 (s, 6H), 0.98 (ddt, J = 14.4, 11.7, 7.4 Hz, 5H), 0.86 (d, J = 6.6 Hz, 3H), 0.59 (s, 3H).

Step 12 Compound (5R)-5-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12aR,12bR)-2,2,5a,7a-tetramethyl-11-oxo-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]hexanoic acid methyl ester I-12 (1.7 g, 3.6 mmol) was dissolved in diethylaminosulfur trifluoride (10 mL), and the resulting mixture was stirred in the reaction solution at 80 ^° C for 1 hour. The reaction was complete as monitored by TLC plate (petroleum ether: ethyl acetate = 10:1). The reaction solution was cooled to room temperature, dichloromethane (50 mL) was added to dilute the reaction system, ice water was carefully added dropwise to quench the reaction, the organic phase was collected by layering, the aqueous layer was extracted with dichloromethane (3×30 mL), the combined organic phases were washed with saturated brine (40 mL), filtered and concentrated to obtain a crude product. The crude product was added to a silica gel column (petroleum ether: ethyl acetate = 93:7) to obtain a colorless transparent solid (5R)-5-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10, 10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]hexanoic acid methyl ester I-13 and (5R)-5-[(3aS,5aR,5bR,7aR,8R,10aR,12aR,12bR)-11-fluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10, A mixture of 10a,12,12a,12b-tetradecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[8-yl]hexanoic acid methyl ester II-1 (1.4 g, purity of I-13 95%, yield calculated based on I-13: 74%). Compound I-13: ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.02 (d, J = 15.0 Hz, 2H), 3.67 (s, 2H), 2.33 – 2.23 (m, 2H), 2.18 – 1.58 (m, 6H), 1.51 (s, 2H), 1.46 – 1.34 (m, 2H), 1.30 (s, 2H), 1.13 (dd, J = 17.2, 7.0 Hz, 1H), 1.07 (s, 1H), 0.93 (d, J = 6.3 Hz, 2H), 0.68 (s, 3H).

In the thirteenth step, the compound (5R)-5-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a, 10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]hexanoic acid methyl ester I-13 and (5R)-5-[(3aS,5aR,5bR,7aR,8R,10aR,12aR, A mixture of 11-fluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10, 10a,12,12a,12b-tetradecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[8-yl]hexanoic acid methyl ester II-1 (1.3 g, 2.6 mmol, 1.0 eq) was dissolved in tetrahydrofuran (50 mL), and lithium aluminum tetrahydrogen (0.3 g, 7.8 mmol, 3eq) was added, and the resulting mixture was stirred in the reaction solution at 25°C for 1 h. The reaction was complete as monitored by TLC (petroleum ether:ethyl acetate = 10:1). The reaction mixture was quenched with sodium sulfate decahydrate, filtered and concentrated to give a white solid (5R)-5-[(3aS,5aR,5bS,7aR, 8R,10aS,10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11, 12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]hexan-1-ol I-14 and (5R)-5-[(3aS,5aR,5bR,7aR,8R,10aR,12aR, 12bR)-11-fluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a, The crude product of 12,12a,12b-tetradecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[8-yl]hexanoic acid methyl ester II-12 (0.9 g, purity 96%, yield: 92%) was directly used for the next step.

Step 14: Compound (5R)-5-[(3aS,5aR,5bS,7aR, 8R,10aS,10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]hexan-1-ol I-14 and (5R)-5-[(3aS,5aR,5bR,7aR,8R,10aR,12aR,12bR)-11-fluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9, 10,10a,12, 12a,12b-tetradecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[8-yl]hexanoic acid methyl ester II-2 mixture (1.3 g, 2.7 mmol, 1.0 eq) was dissolved in dichloromethane (50 mL), and Dessmartin reagent (2.3 g, 5.5 mmol, 2 eq) was added. The resulting mixture was stirred in the reaction solution under N ₂ at 25°C for 1 h. TLC (petroleum ether:ethyl acetate = 10:1) monitored the reaction to be complete. Saturated sodium bicarbonate (10 mL) was added to the reaction system, and the organic phase was extracted with saturated sodium sulfite (3×30 mL). The concentrated organic phase was collected and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 92:8) to obtain a white solid (5R)-5-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR, 12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9, 10,10a,10b,11,12,12a,12b-Hexadecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]hexanal I and (5R)-5-[(3aS,5aR,5bR,7aR,8R,10aR,12aR,12bR )-11-fluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,12,12a,12b-tetradecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta-8-yl]hexanal II mixture (0.95 g, purity of I 90%, yield based on I 66%). Compound I : ¹ H NMR (400MHz, CDCl ₃ ) δ 9.70 (t, J = 1.7Hz, 1H), 3.98 – 3.91 (m, 2H), 2.39 – 2.25 (m, 2H), 1.96 – 1.86 (m, 1H), 1.81 – 1.71 (m, 2H), 1.64 (ddd, J = 10.7, 10.3, 4.7Hz, 1H), 1.57 – 1.52 (m, 1H), 1.44 (s, 2H), 1.38 – 1.28 (m, 2H), 1.23 (s, 1H), 1.18 (d,J = 9.1Hz, 1H), 1.08 – 1.02 (m, 1H), 1.00 (s, 1H), 0.87 (d, J = 6.5Hz, 2H), 0.83 – 0.77 (m, 1H), 0.60 (d, J = 12.0Hz, 2H). Example III Preparation of Intermediate III (5R)-5-[(3aS,5aR,5bS,7aR,8R,10aS,10bS, 12bR)-2,2,5a,7a- tetramethyl -4,5,5a,5b,6,7,7a,8,9,10,10a, 10b,11,12b -tetradecahydro -3aH- cyclopenta [1',2':1,2] phenanthro [7,8-d][1,3] dioxacyclopenta- 8- yl ] hexanal (III)

Step 1: Dissolve compound (5R)-5-[(3aS,5aR,5bS,7aR, 8R,10aS,10bS,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a, 8,9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]hexanoic acid methyl ester I-10 (1 g, 2.18 mmol, 1.0 eq ) in tetrahydrofuran (50 mL), replace the atmosphere with nitrogen, and add lithium aluminum tetrahydrogen (0.12 g, 3.270 mmol, 1.5 eq ), stirred at 25°C for 1 h. The reaction progress was monitored by TLC plate (petroleum ether: ethyl acetate = 5:1), and the raw material was completely consumed. The product was quenched with sodium sulfate decahydrate, filtered, and the filtrate was concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 80:20) to give a white solid (5R)-5-[(3aS,5aR,5bS, 7aR,8R,10aS,10bS,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6, 7,7a,8,9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]hexan-1-ol III-1 (1 g, purity: 90%, yield: 96%). ¹ H NMR (400 MHz, CDCL ³ ) δ 5.80 (d, J 1.67 (m, 8H), 1.41 (td, J = 12.7, 6.2 Hz, 4H), 1.35 (s, 3H), 1.24 (m, 2H), 1.17 (s, 4H), 1.08 (m, 5H), 0.93 (d, J = 6.5 Hz, 4H), 0.69 (d, J = 4.6 Hz, 3H).

Step 2: Dissolve compound (5R)-5-[(3aS,5aR,5bS,7aR, 8R,10aS,10bS,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8, 9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]hexan-1-ol III-1 (1 g, 90% purity, 2.09 mmol) in dichloromethane (50 mL), add Desmartin oxidant (1.18 g, 2.79 mmol), and stir at 25°C for 1 h. TLC (petroleum ether: ethyl acetate = 5:1) was used to monitor the progress of the reaction and the consumption of the starting material. The mixture was quenched with saturated sodium sulfite, water (10 mL) was added to the reaction system, and the aqueous layer was extracted with dichloromethane (3×50 mL). The organic phases were combined and washed with saturated brine (10 mL), dried over anhydrous Na2SO4, filtered, and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 90:10) to give white solid (5R)-5-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a, 8,9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]hexanal III (750 mg, 1.58 mmol, purity: 90%, yield: 68%). ¹ H NMR (400 MHz, CDCL3) δ 9.76 (s, 1H), 5.80 (d, J = 2.7 Hz, 1H), 4.41 (d, J = 5.8 Hz, 1H), 4.10 (dd, J = 13.6, 6.3 Hz, 1H), 2.39 (m, 2H), 2.12 (m, 1H), 2.01 (m, 1H), 1.83 (m, 1H), 1.66 (m, 10H), 1.53 (s, 4H), 1.42 (dd, J = 12.5, 4.2 Hz, 3H), 1.35 (s, 3H), 1.17 (s, 3H), 1.10 (m, 4H), 0.92 (dd, J = 18.2, 5.8 Hz, 4H), 0.71 (d, J = 12.1 Hz, 3H). Examples 9 & 10 Compound 9 3β-[(2- Hydroxyethyl ) oxy ]-5α -cholest -25- ol and Compound 10 {[(1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-1-[(2R)-6- hydroxy - 6- methylhept - 2 - yl ]-9a,11a -dimethylhexadecahydro -1H - cyclopenta [1,2-a] phenanthrene - 7 - yl ] oxy } acetate -2- methylpropan- 2- yl ester

Step 1: Dissolve (1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-methoxy-6-oxyylidenehexan-2-yl]-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate I-7 (80 mg, 0.180 mmol) in tetrahydrofuran (2 mL) and methanol (1 mL), add Pd(OH) ₂ (20 mg, 0.142 mmol), replace the hydrogen atmosphere three times, stir at 40°C for 48 hours, and monitor by HNMR. The reaction solution was filtered and the filtrate was concentrated to obtain (1R, 3aS, 3bR, 7S, 9aS, 9bS, 11aR)-1-[(2R)-6-methoxy-6-oxyylidenehexan-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate 9-1 (80 mg, 94.57%) as an off-white solid. ¹ HNMR(399MHz,cdcl3) δ 4.74 – 4.58 (m, 1H), 3.64 (s, 3H), 2.32 – 2.17 (m, 2H), 2.00 (s, 3H), 1.92 (d,J = 12.7Hz, 1H), 1.78 (d,J = 9.5Hz, 2H), 1.73 – 1.61 (m, 3H), 1.53 (d,J = 10.1Hz, 3H), 1.48 – 1.40 (m, 3H), 1.33 (dd,J = 23.5, 11.4Hz, 4H), 1.24 (d,J = 9.9Hz, 4H), 1.20 – 1.12 (m, 3H), 1.10 – 1.02 (m, 3H), 0.96 (d,J = 15.7Hz, 2H), 0.89 (d,J = 6.3Hz, 3H), 0.79 (s, 3H), 0.62 (s, 3H).

Step 2: Dissolve (1R, 3aS, 3bR, 7S, 9aS, 9bS, 11aR)-1-[(2R)-6-methoxy-6-oxyylidenehexan-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl methyl acetate 9-1 (80 mg, 0.179 mmol) in tetrahydrofuran (3 mL), replace with nitrogen three times, cool to -78 °C, add methyl lithium (0.560 mL, 0.896 mmol), warm to room temperature and stir for 3 hours. Monitor by TLC (petroleum ether: ethyl acetate = 10:1). The reaction solution was quenched by adding water (15 mL), extracted with ethyl acetate (10 mL * 3), washed once with brine, dried over anhydrous sodium sulfate, and concentrated to obtain 80 mg of crude product. Cholesterol-3β,25-diol 9-2 (20 mg, 22.08%) was obtained by column chromatography (DCM:MeOH=300: 1-100:1). ¹ H NMR (399 MHz, CDCl ₃ ) δ 5.32 (s, 0H), 3.56 (s, 1H), 1.93 (d, J = 12.9 Hz, 1H), 1.75 (s, 2H), 1.70 – 1.60 (m, 2H), 1.55 (s, 3H), 1.43 (s, 3H), 1.35 (s, 3H), 1.28 (s, 3H), 1.24 (s, 3H), 1.23 (s, 3H), 1.19 (s, 6H), 1.11 – 1.01 (m, 4H), 0.95 (d, J = 10.9 Hz, 3H), 0.89 (d, J = 6.5 Hz, 3H), 0.77 (s, 3H), 0.62 (s, 3H). ¹³ CNMR (101MHz, CDCl ₃ ) δ 77.31, 77.20, 77.00, 76.68, 71.35, 71.10, 56.45, 56.16, 54.30, 44.81, 44.39, 42.58, 40.00, 38.19, 36.97, 36.39, 35.73, 35.47, 35.43, 32.06, 31.50, 30.95, 29.33, 29.18, 28.71, 28.25, 27.19, 24.19, 21.23, 20.74, 18.61, 12.31, 12.06. LC-MS: [M+Na] ⁺ = 427.15.

Step 3: Dissolve 5α-cholestane-3β,25-diol (10 mg, 0.025 mmol) in toluene (3 mL), add potassium tert-butoxide (14.03 mg, 0.125 mmol), and stir at room temperature for 1 hour. Add tert-butyl bromoacetate (24.38 mg, 0.125 mmol), and stir at room temperature for 2 hours. Monitor by TLC (petroleum ether: ethyl acetate = 3:1). The reaction solution was directly concentrated to obtain 40 mg of crude product, which was purified by column chromatography (ethyl acetate:petroleum ether = 30%) to obtain {[(1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-yl]oxy}acetate-2-methylpropan-2-yl ester 10 (3 mg, 0.005 mmol, 22.23%) as a white solid. Compound 10 : ¹ HNMR (399 MHz, Chloroform-d) δ 3.98 (s, 2H), 3.29 (dt,J = 11.2, 6.2 Hz, 1H), 1.90 (dd,J = 30.3, 12.5 Hz, 2H), 1.79 – 1.67 (m, 2H), 1.62 (d,J = 13.0 Hz, 4H), 1.51 (d,J = 7.2 Hz, 5H), 1.45 (s, 9H), 1.42 (d,J =2.1 Hz, 5H), 1.36 – 1.29 (m, 6H), 1.19 (s, 6H), 1.04 (dt, J = 20.1, 9.4 Hz, 6H), 0.89 (d, J = 6.5 Hz, 3H), 0.84 (d, J = 14.0 Hz, 2H), 0.77 (s, 3H), 0.62 (s, 3H).

Step 4: Dissolve 2-methylpropan-2-yl {[(1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-yl]oxy}acetate 10 (20 mg, 0.039 mmol) in tetrahydrofuran (5 mL), add lithium aluminum tetrahydrogen (4.39 mg, 0.116 mmol), and stir at room temperature for 1 hour. Monitor by TLC (petroleum ether: ethyl acetate = 3:1). The reaction solution was directly concentrated to obtain 10 mg of crude product, which was purified by column chromatography (ethyl acetate:petroleum ether = 40%) to obtain 3β-[(2-hydroxyethyl)oxy]-5α-cholest-25-ol 9 (10 mg, 0.021 mmol, 54.92%) as a white solid. Compound 9 : ¹ H NMR (399 MHz, Chloroform-d) δ 3.69 (t, J = 4.5 Hz, 2H), 3.55 (td, J = 4.5, 2.2 Hz, 2H), 3.29 – 3.20 (m, 1H), 2.10 – 1.91 (m, 2H), 1.87 – 1.75 (m, 2H), 1.71 (dd, J = 13.4, 3.9 Hz, 1H), 1.62 (d, J = 3.3 Hz, 2H), 1.52 (s, 1H), 1.49 – 1.39 (m, 3H), 1.37 (s, 2H), 1.31 (d, J = 6.6 Hz, 2H), 1.27 (d, J = 4.6 Hz, 2H), 1.23 (d, J = 7.1 Hz, 3H), 1.19 (s, 6H), 1.13 – 1.02 (m, 4H), 1.01 – 0.91 (m, 3H), 0.89 (d, J = 6.6 Hz, 3H), 0.88 – 0.79 (m, 2H), 0.78 (s, 3H), 0.63 (s, 3H), 0.58 (dd, J = 10.7, 4.0 Hz, 1H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 79.02, 71.10, 68.82, 62.11, 56.46, 56.18, 54.35, 44.78, 44.39, 42.59, 40.00, 36.91, 36.40, 35.73, 35.46, 34.79, 32.07, 29.32, 29.17, 28.81, 28.24, 24.18, 21.20, 20.74, 18.61, 12.26, 12.0. LCMS: [M+Na] ⁺ =458.39. Example 12 Compound 12 (5R)-5-[(1R,3aS,3bR,5aS,9aS,9bS,11aR)-7- amino- 9a, 11a-dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -1- yl ] hexanoic acid methyl ester

Step 1: Dissolve (1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2R)-6-methoxy-6-oxyylidenehexan-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate I-7 (1 g, 2.249 mmol) in tetrahydrofuran (5 mL) and methanol (5 mL). Add potassium carbonate (3.11 g, 22.489 mmol). Stir at 40°C for 5 hours and monitor by TLC (petroleum ether: ethyl acetate = 3:1). Concentrate the reaction solution to obtain 5 g of crude product. Purification by column chromatography (ethyl acetate/petroleum ether = 40%) gave (5R)-5-[(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-hydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 12-1 (0.8 g, 1.888 mmol, 83.94%) as a white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 5.33 (d, J = 5.1 Hz, 1H), 3.65 (s, 3H), 3.54 – 3.47 (m, 1H), 2.33 – 2.17 (m, 5H), 2.00 – 1.92 (m, 2H), 1.90 – 1.74 (m,4H), 1.67 (d, J = 7.9 Hz, 1H), 1.53 – 1.46 (m, 5H), 1.43 (dd, J = 11.2, 4.6 Hz, 3H), 1.40 – 1.32 (m, 2H), 1.27 – 1.12 (m, 4H), 1.07 (dd, J = 12.8, 7.1 Hz, 4H), 1.03 (d, J = 4.8 Hz, 1H), 0.99 (s, 3H), 0.95 (d, J = 5.9 Hz, 1H), 0.92 (d, J = 6.6 Hz, 3H), 0.85 (dd, J = 24.1, 6.0 Hz, 1H), 0.66 (d, J = 2.2 Hz, 3H).

Step 2: In a 50 mL round-bottom flask at room temperature, (5R)-5-[(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-hydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 12-1 (250 mg, 0.62 mmol) was dissolved in ethyl acetate (10 mL), acetic acid (0.2 mL) and platinum dioxide (125 mg) were added at room temperature, and the mixture was stirred in a hydrogen atmosphere at room temperature for 16 hours. The reaction was detected by TLC (ethyl acetate/petroleum ether = 5:1), and a new compound was generated. After the reaction was completed, the reaction solution was diluted with ethyl acetate (30 mL), filtered through diatomaceous earth, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain white solid (5R)-5-[(1R, 3aS, 3bR, 5aS, 7S, 9aS, 9bS, 11aR)-7-hydroxy-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 12-2 (240 mg, purity: 90%, yield: 85.97%). ¹ H NMR (400 MHz, CDCl3) δ 3.66 (s, 3H), 3.62 – 3.54 (m, 1H), 2.32 – 2.21 (m, 2H), 1.84 – 1.75 (m, 3H), 1.74 – 1.61 (m, 5H), 1.58 – 1.46 (m, 5H), 1.42 – 1.22 (m, 11H), 1.14 – 1.04 (m, 5H), 0.91 (d, J = 6.5 Hz, 3H), 0.80 (s, 3H), 0.64 (s, 3H).

Step 3: In a 50 mL round-bottom flask at room temperature, (5R)-5-[(1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-7-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 12-2 (230 mg, 0.57 mmol) was dissolved in 1,2-dichloroethane (10 mL), and Dess-Martin periodinane (362 mg, 0.85 mmol) was added at room temperature and stirred at 45 °C for 3 hours. The reaction was monitored by TLC (ethyl acetate/petroleum ether = 10:1). After the reaction was completed, the reaction solution was diluted with dichloromethane (10 mL), and a saturated aqueous sodium sulfite solution (20 mL) and a saturated aqueous sodium bicarbonate solution (20 mL) were added to quench the reaction. The mixture was extracted with dichloromethane (20 mL×3), and the organic phase was washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and the organic phase was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) to obtain a white solid (5R)-5-[(1R, 3aS, 3bR, 5aS, 9aS, 9bS, 11aR)-9a, 11a-dimethyl-7-oxyylidene hexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 12-3 (220 mg, purity: 90%, yield: 86.52%). ¹ H NMR (400 MHz, CDCl3) δ = 3.67 (s, 3H), 2.42 – 2.22 (m, 5H), 2.10 – 1.96 (m, 3H), 1.85 – 1.77 (m, 1H), 1.73 – 1.65 (m, 2H), 1.60 – 1.48 (m, 6H), 1.43 – 1.30 (m, 7H), 1.27 – 1.04 (m, 6H), 1.00 (s, 3H), 0.92 (d, J=6.5, 3H), 0.67 (s, 3H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ = 212.15, 174.33, 56.27, 55.93, 53.78, 51.43, 46.70, 44.73, 42.61, 39.87, 38.56, 38.19, 35.65, 35.51, 35.40, 35.39, 34.52, 31.70, 29.70, 28.96, 28.16, 24.20, 21.55, 21.43, 18.55, 12.04, 11.46.

Step 4: In a 50 mL round-bottom flask at room temperature, (5R)-5-[(1R,3aS,3bR,5aS,9aS,9bS,11aR)-9a,11a-dimethyl-7-oxo-ylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 12-3 (190 mg, 0.47 mmol) was dissolved in tetrahydrofuran (3 mL) and methanol (6 mL), and ammonium acetate (363 mg, 4.70 mmol) and a catalytic amount of acetic acid (0.20 mL) were added at room temperature and stirred at room temperature for 2 hours. Then, sodium cyanoborohydride (297 mg, 4.70 mmol) was added to the reaction solution and stirred at room temperature for 14 hours. The reaction was monitored by TLC (dichloromethane/methanol = 10:1). After the reaction was completed, the reaction solution was diluted with dichloromethane (20 mL), and a saturated sodium bicarbonate aqueous solution (30 mL) was added to quench the reaction. The mixture was extracted with dichloromethane (20 mL×3), and the organic phase was washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and the organic phase was concentrated and purified by silica gel column chromatography (dichloromethane: methanol = 10: 1) to obtain white solid (5R)-5-[(1R, 3aS, 3bR, 5aS, 9aS, 9bS, 11aR)-7-amino-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 12-4 (160 mg, purity: 90%, yield: 75.59%). ¹ H NMR (400 MHz, DMSO) δ 7.68 (s, 2H), 3.57 (s, 3H), 2.94 (dd, J = 25.9, 13.9 Hz, 1H), 2.32 – 2.16 (m, 2H), 1.98 – 1.88 (m, 1H), 1.80 – 0.95 (m, 27H), 0.88 (d, J = 6.4 Hz, 3H), 0.76 (s, 3H), 0.62 (s, 3H).

Step 5: In a 50 mL round-bottom flask at room temperature, (5R)-5-[(1R,3aS,3bR,5aS,9aS,9bS,11aR)-7-amino-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 12-4 (160 mg, 0.396 mmol) was dissolved in anhydrous tetrahydrofuran (5 mL). The reaction was cooled to 0 ^° C under nitrogen protection, and 3 mol/L methyl magnesium bromide tetrahydrofuran solution (1.321 mL, 3.963 mmol) was added dropwise. The mixture was then stirred at room temperature for 2 hours. The reaction was monitored by TLC (dichloromethane: methanol = 8:1). After the reaction was completed, the system was cooled to 0 ^°C . C, quenched with saturated aqueous ammonium chloride solution (20 mL), extracted with ethyl acetate (15 mL×3), washed with saturated brine (30 mL) and dried over anhydrous sodium sulfate, purified by silica gel column chromatography (dichloromethane: methanol = 8: 1) to obtain white solid 3-amino-5α-cholest-25-ol (130 mg, purity: 80%, yield: 64.99%). In a 50 mL round-bottom flask at room temperature, (5R)-5-[(1R,3aS,3bR,5aS,9aS,9bS,11aR)-7-amino-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester (160 mg, 0.396 mmol) was dissolved in anhydrous tetrahydrofuran (5 mL). The reaction was cooled to 0 ^° C under nitrogen protection, and 3 mol/L methyl magnesium bromide tetrahydrofuran solution (1.321 mL, 3.963 mmol) was added dropwise. The mixture was then stirred at room temperature for 2 hours. The reaction was monitored by TLC (dichloromethane: methanol = 8:1). After the reaction was completed, the system was cooled to 0 ^°C . C, quenched with saturated aqueous ammonium chloride solution (20 mL), extracted with ethyl acetate (15 mL×3), washed with saturated brine (30 mL) and dried over anhydrous sodium sulfate, purified by silica gel column chromatography (dichloromethane: methanol = 8: 1) to obtain white solid 3-amino-5α-cholest-25-ol 12 (130 mg, purity: 80%, yield: 64.99%). (ESI-MS(M+H)+: 404.4. ¹ H NMR (400 MHz, DMSO) δ 7.61 (s, 2H), 4.03 (s, 1H), 2.93 (m, 1H), 1.93 (d, J = 12.0 Hz, 1H), 1.70 (s, 4H), 1.47 (d, J = 13.4 Hz, 4H), 1.31 (dd, J = 13.5, 6.9 Hz, 6H), 1.18 (m, 10H), 1.05 (s, 6H), 0.99 (m, 4H), 0.89 (d, J = 6.5 Hz, 3H), 0.82 (d, J = 12.6 Hz, 1H), 0.76 (s, 3H), 0.63 (s, 3H). Example 14 Compound 14 Preparation of 1,1,1- trifluoro -N-[(1R,3aS,3bR,5aS,9aS,9bS,11aR)-1-[(2R)-6- hydroxy -6 - methylhept -2- yl ]-9a,11a -dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -7- yl ] methanesulfonamide .

Step 1: In a 50 mL round-bottom flask, 3-amino-5α-cholest-25-ol 12 (20 mg, 0.050 mmol) was dissolved in dichloromethane (1 mL). Triethylamine (15 mg, 0.15 mmol) was added at room temperature. Trifluoromethanesulfonic anhydride (17 mg, 0.059 mmol) was added dropwise at 0 °C. The reaction solution was stirred at 0 °C for 1 hour. The reaction was monitored by TLC (ethyl acetate/petroleum ether = 3:1). After the reaction was completed, water (10 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (5 mL×3). The organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain white solid 1,1,1-trifluoro-N-[(1R,3aS,3bR,5aS,9aS,9bS,11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-yl]methanesulfonamide 14 (5 mg, purity: 91.44%, yield: 17.23%).

Compound 14 : ¹ H NMR (400 MHz, ) δ 4.53 (d, J = 8.7 Hz, 1H), 3.46 (d, J = 8.1 Hz, 1H), 1.94 (dd, J = 17.4, 13.9 Hz, 2H), 1.77 (dd, J = 14.2, 11.3 Hz, 2H), 1.66 (d, J = 10.3 Hz, 2H), 1.45 (d, J = 4.9 Hz, 3H), 1.33 (m, 15H), 1.21 (s, 6H), 1.05 (m, 7H), 0.91 (d, J = 6.5 Hz, 3H), 0.79 (s, 3H), 0.65 (s, 3H). ¹⁹ F NMR (377 MHz, CDCl3) δ -77.92 (s, 3F). Example 18 Preparation of Compound 18 3β-[(3- hydroxypropyl ) oxy ]-5α -cholest -25- ol

Step 1: Dissolve 5α-cholestane-3β,25-diol 9-2 (200 mg, 0.494 mmol) in toluene (10 mL), add potassium tert-butoxide (277.28 mg, 2.471 mmol), and stir at room temperature for 1 hour. Add allyl bromide (298.95 mg, 2.471 mmol), and stir at room temperature for 2 hours. Monitor by TLC (petroleum ether: ethyl acetate = 3:1). The reaction solution is directly concentrated to obtain 40 mg of crude product, which is purified by column chromatography (ethyl acetate: petroleum ether = 30%) to obtain 3β-(prop-2-enyloxy)-5α-cholestane-25-ol 18-1 (70 mg, 0.150 mmol, 30.26%), a white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 5.91 (ddt, J = 16.2, 10.7, 5.6 Hz, 1H), 5.29 – 5.09 (m, 2H), 3.99 (dd, J = 5.6, 1.7 Hz, 2H), 3.25 (dt, J = 11.2, 6.1 Hz, 1H), 1.94 (d, J = 12.4 Hz, 1H), 1.87 – 1.74 (m, 2H), 1.74 –1.57 (m, 4H), 1.50 (d, J = 15.1 Hz, 4H), 1.47 – 1.39 (m, 4H), 1.36 (d, J = 9.0 Hz, 4H), 1.31 (s, 3H), 1.19 (s, 6H), 1.08 (d, J = 8.3 Hz, 2H), 1.03 (d, J = 9.1 Hz, 3H), 0.95 (d, J = 10.6 Hz, 2H), 0.89 (d, J = 6.4 Hz, 3H), 0.87 – 0.79 (m, 2H), 0.77 (s, 3H), 0.62 (s, 3H), 0.57 (d, J = 13.1 Hz, 1H).

Step 2: Dissolve 3β-(prop-2-enyloxy)-5α-cholest-25-ol 18-1 (60 mg, 0.135 mmol) in tetrahydrofuran (3 mL), add borane tetrahydrofuran (1.349 mL, 1.349 mmol), and stir at room temperature for 1 hour. Add sodium hydroxide (0.899 mL, 2.698 mmol) and hydrogen peroxide (152.94 mg, 1.349 mmol), and stir at room temperature for 2 hours. Monitor by TLC (petroleum ether: ethyl acetate = 1:1). The reaction solution was directly concentrated to obtain 400 mg of crude product, which was purified by column chromatography (ethyl acetate:petroleum ether = 50%) to obtain 3β-[(3-hydroxypropyl)oxy]-5α-cholest-25-ol 18 (20 mg, 0.041 mmol, 30.43%) as a white solid. Compound 18 : ¹ H NMR (400 MHz, Chloroform-d) δ 3.76 (t, J = 5.4 Hz, 2H), 3.65 (tq, J = 5.5, 3.2 Hz, 2H), 3.21 (dt, J = 11.1, 6.0 Hz, 1H), 1.94 (dt, J = 12.8, 3.3 Hz, 1H), 1.86 – 1.82 (m, 1H), 1.81 – 1.78 (m, 2H), 1.77 – 1.66 (m, 3H), 1.62 (ddd, J = 12.6, 6.5, 3.1 Hz, 2H), 1.57 – 1.46 (m, 2H), 1.4 11.5 Hz, 2H), 1.38 – 1.30 (m, 5H), 1.27 – 1.22 (m, 4H), 1.19 (s, 6H), 1.13 – 1.06 (m, 2H), 1.05 – 0.91 (m, 5H), 0.89 (d, J = 6.4 Hz, 3H), 0.82 (d, J = 8.4 Hz, 1H), 0.77 (s, 3H), 0.62 (s, 3H), 0.60 – 0.54 (m, 1H). ¹³ C NMR (100 MHz, cdcl3) δ 79.053, 77.192, 71.095, 67.771, 62.813, HPLC: 92.13% (CAD). Example 19 Compound 19 Preparation of {[(1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-1-[(2R)-6- hydroxy -6- methylhept -2- yl ]-9a,11a -dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -7- yl ] oxy } acetic acid .

Step 1: Dissolve 2-methylpropan-2-yl {[(1R, 3aS, 3bR, 5aS, 7S, 9aS, 9bS, 11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-yl]oxy}acetate (140 mg, 0.270 mmol) in dichloromethane (3 mL), add formic acid (6 mL, 0.010 mmol), and stir at room temperature for 1 hour. Monitor by TLC (petroleum ether:ethyl acetate = 3:1). The reaction solution was directly concentrated to give the crude product {[(1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-yl]oxy}acetic acid 19 (140 mg, 0.121 mmol, 44.85%) as a light yellow solid. Compound 19 : ¹ H NMR (400 MHz, Methanol-d4) δ 4.08 (s, 2H), 3.33 (t, J = 5.0 Hz, 1H), 2.01 – 1.96 (m, 1H), 1.84 (d, J = 13.6 Hz, 2H), 1.76 – 1.61 (m, 3H), 1.58 – 1.48 (m, 2H), 1.42 (d, J = 8.9 Hz, 3H), 1.35 (d, J = 20.6 Hz, 4H), 1.29 (d, J = 9.8 Hz, 5H), 1.21 (s, 1H), 1.14 (s, 6H), 1.13 – 1.06 (m, 4H), 1.04 – 0.97 (m, 3H), 0.92 (d, J = 6.6 Hz, 3H), 0.87 (s, 1H), 0.82 (s, 3H), 0.67 (s, 3H), 0.65 – 0.59 (m, 1H). LCMS: [M] ⁺ = 462.37. Example 23 Preparation of Compound 23 3β,25- dihydroxycholesterol -4β-carboxylic acid

Step 1: In a 50 mL round-bottom flask at room temperature, acetic acid-[(1R,3aS,3bS,5aS,7S,9aR,9bS,11aR)-7-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methyl ester 13 (220 mg, 0.46 mmol) was dissolved in dichloromethane (10 mL). Imidazole (157 mg, 2.31 mmol) and tert-butyldimethylsilyl chloride (348 mg, 2.31 mmol) were added at room temperature, followed by stirring at room temperature for 16 hours. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 5:1). After the reaction was completed, the reaction mixture was quenched with water (50 mL), extracted with ethyl acetate (30 mL×3), the organic phase was washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain white solid acetic acid-[(1R, 3aS, 3bS, 5aS, 7S, 9aR, 9bS, 11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methyl ester 23-1 (180 mg, purity: 90%, yield: 59.40 %). ¹ H NMR (400 MHz, CDCl3) δ = 4.24 – 4.05 (m, 2H), 3.71 – 3.59 (m, 1H), 1.95 (s, 3H), 1.82 – 1.20 (m, 25H), 1.17 (s, 6H), 1.10 – 0.93 (m, 5H), 0.87 (d, J=6.5, 3H), 0.84 (s, 9H), 0.69 (s, 3H), 0.59 (s, 3H), 0.00 (d, J=1.3, 6H).

Step 2: In a 50 mL round-bottom flask, acetic acid-[(1R,3aS,3bS,5aS,7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylpropan-2-yl)silyl]oxy}-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methyl ester 23-1 (140 mg, 0.24 mmol) was dissolved in tetrahydrofuran (6 mL), and 1 mol lithium tetrahydroaluminum tetrahydrofuran solution (0.28 mL, 0.28 mmol) was added at room temperature and stirred at room temperature for 0.5 hours. The reaction was monitored by TLC (ethyl acetate/petroleum ether = 3:1). After the reaction was completed, the mixture was quenched with water (50 mL), extracted with ethyl acetate (30 mL×3), the organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain white solid 3β-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4-(hydroxymethyl)-5α-cholestan-25-ol 23-2 (100 mg, purity: 90%, yield: 69.21%). ¹ H NMR (400 MHz, CDCl3) δ = 4.02 (t, J=10.1, 1H), 3.95 – 3.87 (m, 1H), 3.58 (d, J=10.8, 1H), 2.15 – 1.63 (m, 16H), 1.62 – 1.32 (m, 14H), 1.25 (s,9H), 1.21 (s, 6H), 1.13 – 0.94 (m, 7H), 0.91 (d, J=6.5, 3H), 0.68 (s, 3H), 0.63 (s, 3H), 0.00 (s, 6H).

Step 3 In a 50 mL round-bottom flask, 3β-{[dimethyl(2-methylpropan-2-yl)silyl]oxy}-4-(hydroxymethyl)-5α-cholest-25-ol 23-2 (50 mg, 0.091 mmol) was dissolved in tetrahydrofuran (1.5 mL) and dichloromethane (1.5 mL). Desmartin reagent (58 mg, 0.14 mmol) was added at room temperature and stirred at room temperature for 2 hours. The reaction was monitored by TLC (ethyl acetate/petroleum ether = 4:1). After the reaction was completed, the mixture was quenched with water (20 mL), extracted with ethyl acetate (10 mL×3), the organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain white solid 3β-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-25-hydroxy-5α-cholestane-4-carboxaldehyde 23-3 (15 mg, purity: 90%, yield: 27.10%). ¹ H NMR (400 MHz, CDCl3) δ = 9.99 (s, 1H), 3.60 – 3.53 (m, 1H), 2.61 – 2.56 (m, 1H), 2.03 – 1.93 (m, 2H), 1.91 – 1.72 (m, 8H), 1.69 – 1.40 (m, 12H), 1.26 (s, 9H), 1.21 (s, 6H), 1.13 – 0.99 (m, 8H), 0.91 (d, J=6.3, 3H), 0.76 (s, 3H), 0.64 (s, 3H), 0.00 (s, 6H).

Step 4: In a 50 mL round-bottom flask at room temperature, 3β-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-25-hydroxycholest-4β-carboxaldehyde 23-3 (12 mg, 0.022 mmol) was dissolved in tert-butyl alcohol (1 mL) and tetrahydrofuran (0.5 mL), and 2-methylbut-2-ene (10 mg, 0.13 mmol), sodium dihydrogen phosphate (8 mg, 0.066 mmol), sodium chlorite (7 mg, 0.077 mmol) and water (0.25 mL) were added at 0°C, followed by stirring at room temperature for 16 hours. The reaction was monitored by TLC (dichloromethane:methanol=10:1). After the reaction was completed, the mixture was quenched with saturated aqueous sodium sulfite solution (20 mL), extracted with dichloromethane and methanol (dichloromethane: methanol = 10: 1, 10 mL × 3), the organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (dichloromethane: methanol = 10: 1) to obtain white solid 3β,25-dihydroxycholesterol-4β-carboxylic acid 23 (3.65 mg, purity: 100%, yield: 37.09%). Compound 23 : ¹ H NMR (400 MHz, DMSO) δ = 11.86 (s, 1H), 4.49 (s, 1H), 4.03 (s, 1H), 3.50 – 3.43 (m, 1H), 2.55 (d, J=5.2, 1H), 2.25 – 2.03 (m, 2H), 1.92 (d, J=12.0, 1H), 1.87 – 1.69 (m, 2H), 1.65 (d, J=13.0, 2H), 1.58 – 1.19 (m, 21H), 1.05 (s, 6H), 0.88 (d, J=6.4, 3H), 0.83 (s, 3H), 0.61 (s, 1H). ¹³ C NMR (101 MHz, DMSO) δ = 71.37, 69.23, 56.19, 55.54, 54.29, 52.79, 50.66, 47.76, 44.60, 42.52, 38.01, 36.64, 36.13, 35.69, 35.46, 32.81, 31.76,29.88, 29.70, 28.28, 28.01, 27.88, 24.33, 23.18, 21.75, 20.94, 20.72, 18.98, 13.22, 12.32. LC-MS: [M+H-2H ₂ O] ⁺ =413.35 Example 24 Preparation of Compound 24 24,24 -difluorocholest -6(5) -ene -3β,25- diol .

In the first step , zinc (0.61 g, 9.312 mmol) was dissolved in THF (15 mL) and then refluxed for 1 hour under nitrogen protection. Acetic acid-(1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2R)-1-methylpropan-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H- Cyclopenta[1,2-i]phenanthrene-7-yl acetate-(1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2R)-1-formylpropan-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate I-5 A mixture of (1.2 g, 3.104 mmol) and BrCF ₂ CO ₂ Et (1.89 g, 9.312 mmol) was dissolved in THF (3 mL) and then added dropwise to the above zinc solution. The reaction was carried out under reflux for 0.5 h. TLC (petroleum ether: ethyl acetate = 5:1) monitored the completion of the reaction of the raw materials. The reaction solution was poured into water and extracted with ethyl acetate (20 mL x 2). The organic phases were combined and concentrated. The crude product was purified by flash chromatography (petroleum ether: ethyl acetate = 95:5 to 80:20) to obtain white solid (5R)-5-[(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2,2-difluoro-3-hydroxyhexanoic acid ethyl ester 24-1 (700 mg, purity: 90%, yield: 39.74%). ¹ H NMR (400 MHz, CDCl3) δ 5.37 (d, J = 4.5 Hz, 1H), 4.68 – 4.52 (m, 1H), 4.47 – 4.28 (m, 2H), 4.12 (d, J = 7.0 Hz, 1H), 2.32 (d, J = 7.1 Hz, 2H), 2.08 – 1.94 (m, 5H), 1.86 (d, J = 9.6 Hz, 3H), 1.69 (d, J = 13.0 Hz, 2H), 1.60 (td, J = 16.9, 6.6 Hz, 4H), 1.47 (dd, J = 15.7, 11.6 Hz, 3H), 1.37 (t, J = 7.1 Hz, 3H), 1.29 – 1.09 (m, 6H), 1.07 – 0.94 (m, 8H), 0.75 – 0.67 (m, 3H).

In the second step , (5R)-5-[(1R,3aS,3bS,7S, 9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8, 9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2,2-difluoro-3-hydroxyhexanoic acid ethyl ester 24-1 (300 mg, 0.587 mmol) was dissolved in dichloromethane (10 mL), and then di(imidazol-1-yl)methanone (314.08 mg, 1.762 mmol) and DMAP (14.35 mg, 0.117 mmol) were added in sequence. The reaction was refluxed for 12 hours. TLC ( The reaction was monitored by using petroleum ether: ethyl acetate = 3:1. The reaction solution was poured into water and extracted with ethyl acetate (20 mL x 2). The organic phases were combined and concentrated. The crude product was purified by flash chromatography (petroleum ether: ethyl acetate = 95:5-60:40) to obtain a colorless oily liquid (5R)-5-[(1R,3aS,3bS,7S,9aR, 9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8, 9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2,2-difluoro-3-{[(imidazol-1-yl)sulfanylidenemethyl]oxy}hexanoic acid ethyl ester 24-2 (250 mg, Purity: 90%, 61.69%). ¹ H NMR (400 MHz, CDCl3) δ 8.47 (d, J = 9.6 Hz, 1H), 7.67 (d, J = 11.0 Hz, 1H), 7.14 (d, J = 6.8 Hz, 1H), 6.32 – 6.12 (m, 1H), 5.37 (d, J = 4.8 Hz, 1H), 5.30 (s, 2H), 4.68 – 4.54 (m, 1H), 4.32 (q, J = 7.2 Hz, 2H), 2.32 (d, J = 6.8 Hz, 2H), 2.11 (s, 1H), 2.06 – 1.93 (m, 5H), 1.85 (d, J = 10.4 Hz, 3H), 1.73 – 1.39 (m, 9H), 1.35 – 1.24 (m, 5H), 1.22 – 0.94 (m, 13H), 0.68 (t, J = 18.8 Hz, 3H).

Step 3 : (5R)-5-[(1R,3aS,3bS,7S,9aR, 9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8, 9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2,2-difluoro-3-{[(imidazol-1-yl)thioylidenemethyl]oxy}hexanoic acid ethyl ester 24-2 (200 mg, 0.322 mmol) was dissolved in toluene (5 mL), and benzoic acid peroxyanhydride (15.61 mg, 0.064 mmol) and triethylsilyl (299.69 mg, 2.577 mmol) were added in sequence. mmol), and the reaction was carried out under reflux for 18 hours. The reaction was complete as monitored by TLC (petroleum ether: ethyl acetate = 8:1). The reaction solution was poured into water and extracted with ethyl acetate (20 mL x 2). The organic phases were combined and concentrated. The crude product was purified by flash chromatography (petroleum ether: ethyl acetate = 95:5) to obtain (5R)-5-[(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b, 10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2,2-difluorohexanoic acid ethyl ester 24-3 (90 mg, purity: 90%, 50.83%), which was directly used in the next step.

Step 4: Dissolve (5R)-5-[(1R,3aS,3bS,7S,9aR, 9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7, 8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2,2-difluorohexanoic acid ethyl ester 24-3 (70 mg, 0.142 mmol) in THF (4 mL), cool to 0 ^° C, slowly add 3.0 M MeMgBr (0.28 mL) dropwise, and stir at 0 ^° C for 0.5 hours after the addition is complete. After the reaction was completed as monitored by TLC (petroleum ether: ethyl acetate = 5:1), the mixture was quenched with water (10 mL), extracted with ethyl acetate (10 mL x 2), concentrated, and the crude product was purified by flash chromatography (petroleum ether: ethyl acetate = 95:5 to 90:10) to obtain white solid acetic acid-(1R,3aS,3bS,7S,9aR,9bS, 11aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 24-4 (50 mg, 90%, 69.83%). ¹ H NMR (400 MHz, CDCl3) δ 5.46 – 5.27 (m, 1H), 4.76 – 4.47 (m, 1H), 2.33 (s, 2H), 2.08 – 1.95 (m, 5H), 1.86 (d, J = 12.4 Hz, 3H), 1.51 (dt, J = 12.4,7.9 Hz, 13H), 1.31 (s, 8H), 1.14 (s, 3H), 1.02 (s, 4H), 0.94 (d, J = 6.6 Hz, 3H), 0.87 (d, J = 11.6 Hz, 1H), 0.69 (s, 3H).

Step 5 : Acetic acid-(1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 24-4 (60 mg, 0.125 mmol) was dissolved in MeOH (5 mL) and water (1 mL), and then K ₂ CO ₃ (34.5 mg, 0.25 mmol) was added. The reaction was carried out at room temperature for 1 hour. TLC (petroleum ether: ethyl acetate = 3:1) monitored the generation of a new spot. The reaction solution was poured into water and extracted with ethyl acetate (20 mL x 2). The organic phases were combined and concentrated. The crude product was purified by flash chromatography (petroleum ether: ethyl acetate = 95:5-60:40) to obtain white solid 24,24-difluorocholest-6(5)-ene-3β,25-diol 24 (30 mg, 0.065 mmol, 52.05%). Compound 24 : ¹ H NMR (400 MHz, CDCl3) δ 5.35 (d, J = 5.2 Hz, 1H), 3.52 (dd, J = 10.3, 5.6 Hz, 1H), 2.34 – 2.18 (m, 2H), 2.07 – 1.92 (m, 3H), 1.86 (dt, J =13.9, 4.8 Hz, 3H), 1.74 – 1.62 (m, 2H), 1.49 (ddt, J = 18.0, 14.7, 8.8 Hz, 7H), 1.37 – 1.24 (m, 9H), 1.18 – 1.04 (m, 4H), 1.05 – 0.98 (m, 4H), 0.97 –0.89 (m, 4H), 0.67 (d, J = 12.8 Hz, 3H). ¹³ C NMR (101 MHz, CDCl3) δ 140.76, 121.70, 71.81, 56.72, 55.71, 50.01, 42.36, 42.30, 39.75, 37.21, 36.46, 35.37, 31.90, 31.89, 31.66,28.03, 27.32, 26.87, 24.12, 23.60, 21.08, 19.40, 18.46, 11.79. LC-MS: [M+H-H2O] ⁺ = 421.55 Example 25 Preparation of Compound 25 24,24 -difluoro -5α -cholestane -3β,25- diol .

In the first step , the obtained white solid (1R,3aS,3bS,7S, 9aR,9bS,11aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate 24-4 (40 mg, 0.083 mmol) was dissolved in methanol (4 mL) and Pd/C (40 mg) was added. After the addition was completed, the mixture was stirred at room temperature for 3 hours. After the reaction was complete as monitored by TLC (petroleum ether: ethyl acetate = 2:1), the product was filtered and acetic acid-(1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 25-1 (40 mg, 90%, 89.62%) was obtained. The crude product was directly used for the next step.

In the second step , (1R,3aS,3bR,5aS,7S,9aS, 9bS,11aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate 25-1 (40 mg, 0.083 mmol) was dissolved in methanol (5 ml) and water (0.5 ml), and then potassium carbonate (34.36 mg, 0.249 mmol) was added. The reaction was carried out at room temperature for 1 hour, and a new spot was generated by TLC (petroleum ether: ethyl acetate = 3:1). The reaction solution was poured into water and extracted with ethyl acetate (20 ml x 2). The organic phases were combined and concentrated. The crude product was purified by flash chromatography (petroleum ether: ethyl acetate = 95:5-60:40) to obtain white solid 24,24-difluoro-5α-cholestane-3β,25-diol 25 (10 mg, 0.020 mmol, 24.65%). Compound 25 : ¹ H NMR (400 MHz, CDCl3) δ 3.59 (s, 1H), 1.95 (d, J = 12.6 Hz, 2H), 1.71 (ddd, J = 27.4, 24.6, 6.5 Hz, 6H), 1.53 – 1.42 (m, 4H), 1.41 – 1.22 (m, 14H), 1.17– 0.95 (m, 6H), 0.91 (t, J = 8.9 Hz, 4H), 0.80 (s, 3H), 0.66 (s, 4H). LC-MS: [M+H-H2O] ⁺ = 423.55 Example 26 Compound 26 Preparation of 4β- hydroxy -3β -hydroxy -24-( hydroxycyclopropyl )-5α -cholan -7- one .

Step 1 : Dissolve (5R)-5-[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-7-acetyloxy-6-hydroxy-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1, 2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-8 (300 mg, 0.65 mmol) in dichloromethane (20 mL), add 4-dimethylaminopyridine (39.81 mg, 0.03 mmol), triethylamine (197.70 mg, 1.95 mmol) and acetic anhydride (79.78 mg, 0.78 mmol) was added and the mixture was reacted at room temperature for 2 h. The reaction was completed as monitored by TLC (petroleum ether:ethyl acetate=5:1). After washing with dichloromethane and water, the product was dried and concentrated with anhydrous sodium sulfate and purified by column chromatography (petroleum ether:ethyl acetate ~ 20:1) to obtain (5R)-5-[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-6, 7-diethoxy-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1, 2-a]phenanthrene-1-yl]hexanoic acid methyl ester 26-1 (230 mg, 62.2%) as a white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 5.81 – 5.76 (m, 1H), 5.48 (d, J = 3.4 Hz, 1H), 3.64 (s, 3H), 2.35 – 2.18 (m, 2H), 2.04 (s, 3H), 1.99 (s, 3H), 1.87 (dt, J = 13.8, 3.7 Hz, 2H), 1.56 (dd, J = 6.7, 4.2 Hz, 2H), 1.50 – 1.42 (m, 4H), 1.39 – 1.33 (m, 2H), 1.24 – 1.17 (m, 2H), 1.11 (s, 3H), 0.91 (d, J = 6.4 Hz, 3H), 0.65 (s, 3H).

Step 2 : (5R)-5-[(1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-7-acetyloxy-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1, 2-a]phenanthrene-1-yl]hexanoic acid methyl ester 26-1 (100.00 mg, 0.23 mmol) was dissolved in acetone (3.0 mL) under nitrogen protection, N-hydroxyphthalimide (3.25 mg, 0.02 mmol), cobalt acetate (0.35 mg, 0.01 tert-Butyl peroxide (85 mg, 0.90 mmol) was then added and the reaction was carried out at room temperature for 16 h. The reaction was complete as monitored by TLC (petroleum ether:ethyl acetate = 10:1). Sodium thiosulfate was added to quench the mixture, and the mixture was extracted with ethyl acetate. The mixture was dried over anhydrous sodium sulfate, concentrated, and column chromatographed with petroleum ether:ethyl acetate (100%~20%) to obtain (5R)-5-[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-6, 7-diethoxy-9a, 11a-dimethyl-4-oxyylidene-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1, 2-a]phenanthrene-1-yl]hexanoic acid methyl ester 26-2 (40 mg, 0.07 mmol, 35.0%) . ¹ H NMR (399 MHz, Chloroform-d) δ 5.90 (s, 1H), 5.60 – 5.56 (m, 1H), 4.80 – 4.74 (m, 1H), 3.64 (d, J = 0.8 Hz, 3H), 2.38 – 2.22 (m, 4H), 2.07 (d, J = 0.8 Hz, 3H), 2.06 – 2.02 (m, 1H), 2.00 (s, 3H), 1.98 – 1.85(m, 2H), 1.77 (dd, J = 13.0, 4.0 Hz, 1H), 1.47 – 1.32 (m, 3H), 1.29 (s, 3H), 1.23 (d, J = 8.5 Hz, 2H), 1.14 – 1.04 (m, 3H), 0.92 (d, J = 6.5 Hz, 3H), 0.65 (s, 3H).

Step 3 : Dissolve (5R)-5-[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-6, 7-diethoxy-9a, 11a-dimethyl-4-oxyylidene-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1, 2-a]phenanthren-1-yl]hexanoic acid methyl ester 26-2 (300 mg, 0.65 mmol) in methanol (10.0 mL), Pd/C 10% (20 mg, 0.19 mmol), replaced with hydrogen three times, reacted at room temperature for 1 h, and the reaction was completed by TLC (petroleum ether: ethyl acetate = 5:1). Filtered through diatomaceous earth, rinsed with methanol, concentrated, and column chromatographed with petroleum ether: ethyl acetate (100%~20%) to obtain (5R)-5-[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-6,7-diacetyloxy-9a, 11a-dimethyl-4-oxyylidene hexahydro-1H-cyclopenta[1, 2-a]phenanthrene-1-yl]hexanoic acid methyl ester 26-3 (50 mg) as a white solid, which was directly used in the next step. ¹ H NMR (399 MHz, Chloroform-d) δ 5.15 (s, 1H), 4.76 (dt, J = 12.3, 4.2 Hz, 1H), 3.65 (s, 3H), 2.49 (t, J = 13.5 Hz, 1H), 2.33 – 2.16 (m, 4H), 2.09 (s, 3H), 2.06 (dd, J = 13.0, 3.1 Hz, 1H), 1.96 (s, 3H), 1.92 (d, J = 3.7 Hz, 1H), 1.90 – 1.80 (m, 3H), 1.74 – 1.63 (m, 3H), 1.49 (dd, J = 9.8, 6.4 Hz, 3H), 1.37 (td, J = 11.7, 11.3, 7.0 Hz, 3H), 1.26 (s, 3H), 1.17 (d, J = 12.5 Hz, 2H), 1.12 – 1.03 (m, 5H), 0.91 (d, J = 6.4Hz, 3H), 0.62 (s, 3H).

Step 4 : Dissolve (5R)-5-[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-6,7-diethoxy-9a, 11a-dimethyl-4-oxyylidenehexahydro-1H-cyclopenta[1, 2-a]phenanthrene-1-yl]hexanoic acid methyl ester 26-3 (50 mg, 0.10 mmol) in toluene (5 mL), add ethylene glycol (0.05 mL, 0.96 mmol), anhydrous p-toluic acid (7.3 mg, 0.05 mmol), heat and reflux and stir for 1 h. Monitor the reaction by TLC (petroleum ether: ethyl acetate = 2:1). Water was added, and the mixture was extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated on a column chromatography with petroleum ether:ethyl acetate (100%~20%) to obtain (5R)-5-[(1'R, 3a'S, 3b'S, 6'R, 7'S, 9a'R, 9b'S, 11a'R)-6', 7'-diacetyloxy-9a',11a'-dimethyl-1', 2', 3', 3a', 3b', 5', 5a', 6', 7', 8', 9', 9a', 9b', 10', 11', 11a'-hexadecylspiro[1, 3-dioxacyclopentane-2, 4'-cyclopenta[1, 2-a]Phenanthrene-1'-yl]hexanoic acid methyl ester 26-4 (8 mg, 0.01 mmol, 17.2%) white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 5.14 (s, 1H), 4.76 (dt, J = 12.0, 4.3 Hz, 1H), 3.97 – 3.84 (m, 5H), 3.63 (s, 3H), 2.05 (s, 3H), 1.94 (s, 2H), 1.02 (s, 3H), 0.90 (d, J = 6.5 Hz, 3H), 0.62 (s, 3H)

Step 5 : Dissolve the compound (5R)-5-[(1'R, 3a'S, 3b'S, 6'R, 7'S, 9a'R, 9b'S, 11a'R)-6', 7'-diethoxy-9a',11a'-dimethyl-1', 2', 3', 3a', 3b', 5', 5a', 6', 7', 8', 9', 9a', 9b', 10', 11', 11a'-hexahydrospiro[1, 3-dioxacyclopentane-2, 4'-cyclopenta[1, 2-a]phenanthrene]-1'-yl]hexanoic acid methyl ester 26-4 (20 mg, 0.04 mmol) in tetrahydrofuran (5 mL), add tetraisopropyl titanium acid (95.6 mg, 0.67 mmol) at room temperature, replace with nitrogen three times, cool to 0°C, add ethyl magnesium chloride (0.62 mL) dropwise, stir at room temperature for 1 h, and monitor by TLC (petroleum ether: ethyl acetate = 3:1). The mixture was quenched by adding salt water at low temperature, diluted by adding ethyl acetate, dried over anhydrous sodium sulfate, concentrated, and column chromatographed with petroleum ether:ethyl acetate (100%-50%) to obtain (1'R, 3a'S, 3b'S, 5a'R, 6'R, 7'S, 9a'R, 9b'S, 11a'R)-1'-[(2R)-5-(hydroxycyclopropyl)pentan-2-yl]-9a', 11a'-dimethyl-1', 2', 3', 3a', 3b', 5', 5a', 6', 7', 8', 9', 9a', 9b', 10', 11', 11a'-hexahydrospiro[1, 3-Dioxacyclopentane-2, 4'-cyclopenta[1,2-a]phenanthrene]-6',7'-diol 26-5 (15.0 mg, 0.03 mmol, 33.6%) as a white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 3.96 (d, J = 5.9 Hz, 4H), 3.67 (s, 1H), 1.94 (d, J = 12.9 Hz, 2H), 1.80 (d, J = 13.0 Hz, 5H), 1.73 (d, J = 10.9 Hz, 5H), 1.44 (d, J = 7.8 Hz, 6H), 1.35 (s, 8H), 1.24 (s,3H), 1.04 (s, 3H), 0.92 (d, J = 6.2 Hz, 3H), 0.84 (t, J = 7.8 Hz, 4H), 0.71 (s, 2H), 0.64 (s, 3H), 0.42 (s, 2H)

Step 5 : (1'R, 3a'S, 3b'S, 5a'R, 6'R, 7'S, 9a'R, 9b'S, 11a'R)-1'-[(2R)-5-(hydroxycyclopropyl)pent-2-yl]-9a', 11a'-dimethyl-1', 2', 3', 3a', 3b', 5', 5a', 6', 7', 8', 9', 9a', 9b', 10', 11', 11a'-hexahydrospiro[1, 3-dioxacyclopentane-2, 4'-cyclopenta[1,2-a]phenanthrene]-6', 7'-diol 26-5 (10 mg, 0.02 mmol) was dissolved in methanol (3.0 mL), acetic acid (2 mL, 34.94 mmol) was added at room temperature, and stirred for 1 h at room temperature. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 1:1). The mixture was quenched by adding brine at low temperature, diluted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated, and column chromatography with petroleum ether: ethyl acetate (100%-50%) gave 4β-hydroxy-3β-hydroxy-24-(hydroxycyclopropyl)-5α-cholan-7-one 26 (3 mg, 0.01 mmol, 19.3%) . Compound 26 : ¹ H NMR (399 MHz, Chloroform-d) δ 3.70 (s, 1H), 3.57 (d, J = 10.6 Hz, 1H), 2.86 (t, J = 13.5 Hz, 1H), 2.37 (t, J = 11.3 Hz, 1H), 2.21 (d, J = 12.1 Hz, 1H), 2.14 – 2.02 (m, 2H), 1.97 (d, J = 13.1 Hz, 1H), 1.79 (ddt,J = 45.8, 32.3, 14.7 Hz,4H), 1.58 – 1.38 (m, 9H), 1.27 (s, 6H),1.11 – 0.96 (m, 13 C NMR ( ¹⁰¹ ) MHz, cdcl3) δ 212.83, 77.31, 77.20, 76.99, 76.67, 74.71, 73.76, 71.92, 55.93, 55.76, 54.82, 50.03, 48.95, 43.78, 42.51, 38.80, 38.60, 36.52, 36.06, 35.89, 35.88, 35.62, 35.55, 31.03, 29.68, 28.40, 25.58,24.99, 22.29, 21.09, 18.74, 14.16, 13.57, 13.48, 12.04, 7.80, 1.00. LC-MS: [M+H] ⁺ =433.3. Example 27 Compound 27 Preparation of 3-{[(1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-1-[(2R)-6- hydroxy -6- methylhept -2- yl ]-9a,11a -dimethylhexadecahydro-1H - cyclopenta [1,2-a] phenanthrene -7- yl ] oxy } propanoic acid .

Step 1: Dissolve 3β-[(3-hydroxypropyl)oxy]-5α-cholest-25-ol 18 (70 mg, 0.151 mmol) in dichloromethane (5 mL), add Dess-Martin periodinane (64.16 mg, 0.151 mmol), and stir at room temperature for 1 hour. Monitor by TLC (petroleum ether: ethyl acetate = 1:1). The reaction solution was directly concentrated to obtain 100 mg of crude product, which was purified by column chromatography (ethyl acetate:petroleum ether = 30%) to obtain 3-{[(1R, 3aS, 3bR, 5aS, 7S, 9aS, 9bS, 11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1, 2-a]phenanthrene-7-yl]oxy}propanal 27-1 (50 mg, 0.103 mmol, 68.15%) as a white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 9.77 (t, J = 2.0 Hz, 1H), 3.78 (td, J = 6.3, 3.1 Hz, 2H), 3.22 (dt, J = 11.5, 6.2 Hz, 1H), 2.63 (td, J = 6.2, 2.0 Hz, 2H), 1.94 (d, J = 12.5 Hz, 1H), 1.81 (d, J = 13.9 Hz, 2H), 1.73 –1.60 (m, 3H), 1.58 – 1.44 (m, 3H), 1.36 (q, J = 13.9, 12.9 Hz, 5H), 1.12 (d, J = 26.3 Hz, 2H), 1.04 (t, J = 9.5 Hz, 3H), 0.96 (d, J = 20.8 Hz, 2H), 0.89 (d, J = 6.3 Hz, 3H), 0.82 (dd, J = 16.9, 8.3 Hz, 2H), 0.76 (s, 3H), 0.62 (s, 3H), 0.59 (s, 1H).

Step 2: 3-{[(1R, 3aS, 3bR, 5aS, 7S, 9aS, 9bS, 11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1, 2-a]phenanthrene-7-yl]oxy}propanal 27-1 (45 mg, 0.098 mmol) was dissolved in tert-butanol (4 mL) and water (0.5 mL), and sodium dihydrogen phosphate (43.19 mg, 0.360 mmol), 2-methyl-2-butene (137.01 mg, 1.953 mmol), and sodium chlorite (26.50 mg, 0.293 mmol) were added and stirred at room temperature for 1 hour. Monitored by TLC (dichloromethane: methanol = 20: 1). Diluted with water, extracted three times with ethyl acetate, the organic phase was washed once with brine, dried over anhydrous sodium sulfate, concentrated to obtain 20 mg of solid, purified by column chromatography (methanol/dichloromethane = 10%) to obtain 3-{[(1R, 3aS, 3bR, 5aS, 7S, 9aS, 9bS, 11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexahydro-1H-cyclopenta[1, 2-a]phenanthrene-7-yl]oxy}propanoic acid 27 (24 mg, 0.048 mmol, 48.97%) as a white solid. Compound 27 : ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 3.71 (t, J = 6.3 Hz, 2H), 3.25 (d, J = 10.9 Hz, 1H), 2.48 (t, J = 6.3 Hz, 2H), 2.02 – 1.95 (m, 1H), 1.88 – 1.77 (m, 2H), 1.76 – 1.64 (m, 2H), 1.64 – 1.55 (m, 2H), 1.50 (dd, J = 13.2, 4.1 Hz, 1H), 1.42 (d, J = 8.9 Hz, 2H), 1.38 (t, J = 4.0 Hz, 2H), 1.35 – 1.32 (m, 2H), 1.27 (t, J = 12.4 Hz, 5H), 1.19 (d, J = 10.9 Hz, 2H), 1.14 (s, 6H), 1.13 – 1.07 (m, 3H), 1.07 – 0.94 (m, 4H), 0.92 (d, J = 6.6 Hz, 3H), 0.90 – 0.83 (m, 1H), 0.80 (s, 3H), 0.67 (s, 3H), 0.62 (d, J = 16.2 Hz, 1H). ¹³ C NMR (101 MHz, cd3od) δ 174.242, 78.790, 70.026, 63.304, 56.451, 56.228, 54.382, 44.646, 43.843, 42.334, 39.970, 36.684, 36.350, 35.704, 35.429, 35.378, 34.873, 34.432, 31.875, 28.548, 27.897, 27.806, 27.780, 27.664, 23.804, 20.894, 20.416, 17.736, 11.265, 11.060. LCMS: [Ms-H] ^- =475.45. Example 29 Preparation of Compound 29 3β-[(2- hydroxyethyl ) oxy ]-5α- cholestane -4β,25- diol

Step 1: Weigh (1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-methoxy-6-oxyylidenehexan-2-yl]-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate I-7 (77 mg, 0.17 mol, 1.0 eq.) and dissolve it in tetrahydrofuran (2 mL). After nitrogen substitution, cool the mixture to -78°C with dry ice-acetone and add methyl lithium (0.54 mL, 0.87 mmol), then heated to room temperature with stirring, monitored by TLC (petroleum ether: ethyl acetate = 10:1). After the reaction was completed, 6 mL of water was added to quench the reaction, and 5 mL*3 of ethyl acetate was used for extraction. The organic phase was dried and concentrated. The crude product was purified by column chromatography (dichloromethane: methanol = 300:1~100:1) to obtain cholester-5(6)-ene-3β,25-diol 29-1 (35 mg, 0.083 mmol, 47.66%) as a white solid. ¹ HNMR(399MHz,cdcl3) δ 5.32 (s, 1H), 3.50 (s, 1H), 2.24 (m, 2H), 1.98 (dd,J = 18.6, 10.9Hz, 2H), 1.82 (d,J = 10.3Hz, 3H), 1.53 (d,J = 10.0Hz, 3H), 1.46 (d,J = 7.2Hz, 3H), 1.42 (d,J = 10.1Hz, 3H), 1.36 (d,J = 12.5Hz, 4H), 1.21 (s, 3H), 1.19 (s, 6H), 1.12 (dd,J = 14.4, 7.2Hz, 2H), 1.03 (m, 4H), 0.99 (s, 3H), 0.91 (d,J = 6.6Hz, 3H), 0.66 (s, 3H). ¹³ C NMR (100MHz, cdcl3) δ 140.72, 121.68, 77.31, 77.00, 76.68, 71.76, 71.11, 56.70, 56.00, 50.05, 44.38, 42.57, 42.29, 42.25, 39.72, 37.20, 36.46, 36.39, 35.72, 31.87, 31.85, 31.61, 29.34, 29.17, 28.70, 28.23, 24.26, 21.04, 20.72, 19.38, 18.66, 11.84.

Step 2: Cholester-5(6)-ene-3β,25-diol 29-1 (1280 mg, 3.179 mmol, 1.0 eq.) was dissolved in toluene (50 mL), potassium tert-butoxide (3567.00 mg, 31.789 mmol, 10.0 eq.) was added, and the mixture was stirred at room temperature for 1 hour. Then tert-butyl bromoacetate (6200.69 mg, 31.789 mmol, 10.0 eq.) was added, and the mixture was stirred at room temperature for 2 hours. TLC (petroleum ether: ethyl acetate = 3:1) was used for monitoring. The reaction solution was directly concentrated to obtain a crude product, which was purified by column chromatography (ethyl acetate:petroleum ether = 30%) to obtain {[(1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1, 2-a]phenanthrene-7-yl]oxy}acetate-2-methylpropan-2-yl ester 29-2 (950 mg, 1.746 mmol, 54.93%) as a white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 5.33 (d, J = 5.0 Hz, 1H), 3.98 (s, 2H), 3.27 – 3.15 (m, 1H), 2.42 – 2.33 (m, 1H), 2.24 (t, J = 12.2 Hz, 1H), 1.95 (q, J = 12.5 Hz, 3H), 1.86 – 1.73 (m, 2H), 1.62 – 1.50 (m, 3H), 1.48 (s, 2H), 1.45 (s, 9H), 1.43 – 1.41 (m, 3H), 1.39 – 1.33 (m, 5H), 1.19 (s, 7H), 1.15 – 1.08 (m, 2H), 1.07 – 1.00 (m, 3H), 0.98 (s, 3H), 0.91 (d, J = 6.5 Hz, 3H), 0.65 (s, 3H).

Step 3: Dissolve 2-methylpropan-2-yl {[(1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1, 2-a]phenanthrene-7-yl]oxy}acetate 29-2 (950 mg, 1.746 mmol, 54.93%) in dichloromethane (15 mL), add pyridine (0.740 mL, 9.191 mmol, 5.0 eq.), acetyl chloride (0.392 mL, 5.515 mmol, 3.0 eq.). Stir at 40°C for 5 hours. Monitor by TLC (petroleum ether: ethyl acetate = 5:1). The reaction solution was directly concentrated to obtain a crude product, which was purified by column chromatography (ethyl acetate:petroleum ether = 20%) to obtain {[(1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-acetyloxy-6-methylhept-2-yl]-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1, 2-a]phenanthrene-7-yl]oxy}acetate-2-methylpropan-2-yl ester 29-3 (760 mg, 70.28%) as a white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 5.33 (s, 1H), 3.98 (s, 2H), 3.26 – 3.16 (m, 1H), 2.41 – 2.32 (m, 1H), 2.24 (t, J = 12.4 Hz, 1H), 2.00 (d, J = 3.9 Hz, 1H), 1.95 (s, 3H), 1.88 (d, J = 15.1 Hz, 1H), 1.83 – 1.70 (m, 2H), 1.68 – 1.61 (m, 1H), 1.59 – 1.49 (m, 4H), 1.45 (d, J = 1.8 Hz, 9H), 1.40 (s, 6H), 1.37 – 1.30 (m, 3H), 1.29 – 1.17 (m, 2H), 1.17 – 1.09 (m, 2H), 1.04 (dd, J = 12.3, 10.5 Hz, 3H), 0.98 (s, 3H), 0.89 (d, J = 6.3 Hz, 3H), 0.65 (s, 3H).

Step 4: Dissolve 2-methylpropan-2-yl {[(1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-acetyloxy-6-methylhept-2-yl]-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1, 2-a]phenanthrene-7-yl]oxy}acetate 29-3 (760 mg, 1.360 mmol, 1.0 eq.) in chloroform (5 mL), add N-methylmorpholine (825.36 mg, 8.160 mmol, 6.0 eq.), selenium dioxide (198.55 mg, 1.789 mmol, 5.0 eq.). Stir at 75°C for 18 hours. Monitor by TLC (petroleum ether: ethyl acetate = 5:1). The reaction solution was directly concentrated to obtain a crude product, which was purified by column chromatography (ethyl acetate:petroleum ether = 40%) to obtain {[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-acetyloxy-6-methylhept-2-yl]-6-hydroxy-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1, 2-a]phenanthrene-7-yl]oxy}acetate-2-methylpropan-2-yl ester 29-4 (320 mg, 38.89%) as a white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 5.68 (d, J = 4.5 Hz, 1H), 4.19 – 4.11 (m, 2H), 3.93 (d, J = 16.8 Hz, 1H), 3.26 (d, J = 11.6 Hz, 1H), 2.10 – 2.03 (m, 1H), 1.99 (d, J = 12.5 Hz, 2H), 1.95 (s, 3H), 1.83 (d, J = 14.2 Hz, 2H), 1.66 (d, J = 14.3 Hz, 3H), 1.52 (d, J = 11.1 Hz, 3H), 1.46 (s, 9H), 1.40 (s, 6H), 1.34 (d, J = 6.7 Hz, 2H), 1.24 (d, J = 8.7 Hz, 1H), 1.18 (s, 3H), 1.12 (t, J = 14.3 Hz, 2H), 1.06 – 1.01 (m, 2H), 1.00 – 0.93 (m, 2H), 0.89 (d, J = 6.4 Hz, 3H), 0.88 – 0.79 (m, 1H), 0.65 (s, 3H).

Step 5: 2-methylpropan-2-yl {[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-acetyloxy-6-methylhept-2-yl]-6-hydroxy-9a, 11a-dimethyl-2, 3, 3a, 3b, 4, 6, 7, 8, 9, 9a, 9b, 10, 11, 11a-tetradecahydro-1H-cyclopenta[1, 2-a]phenanthrene-7-yl]oxy}acetate 29-4 (320 mg, 0.557 mmol, 1.0 eq.) was dissolved in ethyl acetate (10 mL) and acetic acid (2 mL). Platinum dioxide (160 mg, 0.705 mmol, 1.3 eq.). Stirred at 40°C for 15 min under hydrogen atmosphere. Monitored by TLC (petroleum ether: ethyl acetate = 5:1). The reaction solution was filtered, and the filtrate was concentrated to obtain a crude product, which was purified by column chromatography (ethyl acetate: petroleum ether = 30%) to obtain {[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-acetyloxy-6-methylhept-2-yl]-6-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1, 2-a]phenanthrene-7-yl]oxy}acetate-2-methylpropan-2-yl ester 29-5 (200 mg, 0.329 mmol, 59.17%) as a white solid. ¹ H NMR (400 MHz, Chloroform-d) δ 4.15 (d, J = 16.6 Hz, 1H), 3.90 (d, J = 16.8 Hz, 1H), 3.74 (s, 1H), 3.22 (d, J = 11.4 Hz, 1H), 1.95 (d, J = 1.1 Hz, 3H), 1.90 (d, J = 12.8 Hz, 1H), 1.80 (d, J = 13.4 Hz, 2H), 1.73 (dd, J = 13.3, 8.3 Hz, 4H), 1.63 (dd, J = 11.8, 7.8 Hz, 3H), 1.59 – 1.48 (m, 2H), 1.45 (d, J = 1.2 Hz, 9H), 1.39 (d, J = 1.2 Hz, 6H), 1.34 (d, J = 3.7 Hz, 5H), 1.27 – 1.21 (m, 3H), 1.16 – 1.06 (m, 2H), 1.02 (s, 3H), 0.99 – 0.91 (m, 3H), 0.88 (d, J = 6.4 Hz, 3H), 0.80 (d, J = 14.0 Hz, 1H), 0.63 (s, 3H), 0.57 – 0.49 (m, 1H).

Step 6: Dissolve {[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-acetyloxy-6-methylhept-2-yl]-6-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1, 2-a]phenanthrene-7-yl]oxy}acetate-2-methylpropan-2-yl ester 29-5 (40 mg, 0.069 mmol, 1.0 eq.) in tetrahydrofuran (5 mL), add lithium aluminum tetrahydrogen (13.16 mg, 0.347 mmol, 5.0 eq.). Stir at room temperature for 1 h. Monitor by TLC (petroleum ether: ethyl acetate = 5:1). The reaction solution was quenched with water, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by column chromatography (ethyl acetate: petroleum ether = 50%) to obtain 3β-[(2-hydroxyethyl)oxy]-5α-cholestane-4β,25-diol 29 (20 mg, 0.041 mmol, 58.96%) as a white solid. Compound 29 : ¹ H NMR (399 MHz, Chloroform-d) δ3.88 (s, 1H), 3.73 (q, J=3.8, 3.3 Hz, 2H), 3.62 (t, J=4.6 Hz, 2H), 3.25 (dt, J=11.9, 4.3 Hz, 1H), 1.94 (d, J=12.3 Hz, 1H), 1.83–1.73 (m, 5H), 1.70 (s, 6H), 1.54 (d, J = 9.1Hz, 1H), 1.41 (s, 2H), 1.36 (d, J=13.0 Hz, 5H), 1.30–1.22 (m, 2H), 1.19 (s, 6H), 1.07 (d, J=5.7 Hz, 2H), 1.02 (s, 3H), 0.95 (d, J=17.5 Hz, 2H), 0.90 (d, J=6.5 Hz, 3H), 0.88–0.80 (m, 1H), 0.63 (s, 3H), 0.60–0.51 (m, 1H). LCMS: [M-OH-H ₂ O] ⁺ =429.40; CAD: 92.03%. Example 31 Preparation of Compound 31 25- hydroxy -3β-[(2- hydroxyethyl ) oxy ]-5α -cholest -4- one .

Step 1: Dissolve 3β-[(2-hydroxyethyl)oxy]-5α-cholestane-4β, 25-diol 29 (86 mg, 0.185 mmol, 1.0 eq.) in dichloromethane (5 mL), add imidazole (62.99 mg, 0.925 mmol, 5.0 eq.) and tert-butyldimethylsilyl chloride (83.67 mg, 0.555 mmol, 3.0 eq.). Stir at room temperature for 2 h. Monitor by TLC (petroleum ether: ethyl acetate = 5:1). The reaction solution was concentrated to obtain a crude product, which was purified by column chromatography (ethyl acetate:petroleum ether = 20%) to obtain 3β-[(4, 4, 5, 5-tetramethyl-3-oxa-4-silanol-1-yl)oxy]-5α-cholestane-4β, 25-diol 31-1 (65 mg, 0.107 mmol, 57.63%) as a white solid. ¹ H NMR (400 MHz, Chloroform-d) δ 3.84 (s, 1H), 3.72 (dq, J = 11.5, 6.8, 6.4 Hz, 2H), 3.55 (d, J = 10.4 Hz, 2H), 3.22 (d, J = 11.1 Hz, 1H), 1.93 (d, J = 12.3 Hz, 1H), 1.74 (dt, J = 24.6, 12.8 Hz, 5H), 1.36 (s, 5H), 1.23 (s, 2H), 1.19 (s, 6H), 1.06 (s, 3H), 1.01 (s, 3H), 0.95 (d, J = 14.0 Hz, 2H), 0.91 – 0.87 (m, 12H), 0.63 (s, 3H), 0.54 (d, J = 3.1 Hz, 1H), 0.05 (s, 6H).

Step 8: Dissolve 3β-[(4, 4, 5, 5-tetramethyl-3-oxa-4-silanol-1-yl)oxy]-5α-cholest-4β, 25-diol 31-1 (60 mg, 0.104 mmol, 1.0 eq.) in dichloromethane (1 mL) and add Dess-Martin periodinane (43.95 mg, 0.104 mmol, 1.0 eq.). Stir at room temperature for 1 h. Monitor by TLC (petroleum ether: ethyl acetate = 5:1). The reaction solution was concentrated to obtain a crude product, which was purified by column chromatography (ethyl acetate:petroleum ether = 20%) to obtain 25-hydroxy-3β-[(4, 4, 5, 5-tetramethyl-3-oxa-4-silanol-1-yl)oxy]-5α-cholest-4-one 31-2 (50 mg, 0.082 mmol, 79.44%) as a white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 4.01 (dd, J = 12.1, 7.1 Hz, 1H), 3.83 – 3.73 (m, 3H), 3.44 (dt, J = 11.3, 5.2 Hz, 1H), 2.25 (s, 1H), 2.02 (dd, J = 38.0, 12.2 Hz, 2H), 1.83 (dd, J = 37.0, 11.2 Hz, 3H), 1.72 (d, J = 13.6 Hz, 3H), 1.50 (d, J = 20.7 Hz, 4H), 1.38 (dd, J = 18.2, 9.9 Hz, 4H), 1.25 (d, J = 10.6 Hz, 3H), 1.20 (s, 6H), 1.15 – 1.06 (m, 2H), 1.06 – 0.95 (m, 3H), 0.91 – 0.88 (m, 3H), 0.87 (s, 9H), 0.78 (d, J = 3.9 Hz, 1H), 0.70 (s, 3H), 0.63 (s, 3H), 0.04 (d, J = 2.8 Hz, 6H).

Step 9: Dissolve 25-hydroxy-3β-[(4, 4, 5, 5-tetramethyl-3-oxa-4-silanol-1-yl)oxy]-5α-cholest-4-one 31-2 (40 mg, 0.069 mmol, 1.0 eq.) in tetrahydrofuran (2 mL) and add tetrabutylammonium fluoride (0.5 mL, 0.500 mmol, 7.2 eq.). Stir at room temperature for 1 h. Monitor by TLC (petroleum ether: ethyl acetate = 3:1). Water was added to the reaction solution, and the mixture was extracted with ethyl acetate three times. The organic phase was dried and concentrated to obtain a crude product, which was purified by column chromatography (methanol/ethyl acetate = 5%) to obtain 25-hydroxy-3β-[(2-hydroxyethyl)oxy]-5α-cholest-4-one 31 (12 mg, 0.025 mmol, 35.54%) as a white solid. Compound 31 : ¹ H NMR (400 MHz, Methanol-d4)δ4.08 (dd, J =11.8, 7.2 Hz, 1H), 3.70–3.59 (m, 3H), 3.52 (dd, J = 9.3, 3.4 Hz, 1H), 2.35–2.22 (m, 2H), 2.20–1.96 (m, 2H), 1.95–1.77 (m, 2H), 1.76–1.61 (m, 2H), 1.55 (dq, J =19.4, 6.4 Hz, 4H), 1.40 (d, J =9.3 Hz, 3H), 1.34–1.30 (m, 3H), 1.27 (d, J = 4.0 Hz, 3H), 1.19 (d, J = 12.7 Hz, 1H), 1.15 (s, 6H), 1.08 (d, J = 13.2 Hz, 2H), 1.03–0.96 (m, 2H), 0.93 (d, J = 6.4 Hz, 3H), 0.90–0.80 (m, 2H), 0.69 (d, J = 11.8 Hz, 6H). LCMS: [M+H] ⁺ = 463.40; CAD: 80.15%. Example 33 Compound 33 Preparation of [(1R,3aS,3bS,5aS,7S,9aR,9bS,11aR)-7- hydroxy -1-[(2R)-6- hydroxy -6- methylhept -2- yl ]-9a,11a -dimethylhexadecahydro -1H - cyclopenta [1,2-a] phenanthrene -6- yl ] acetonitrile

Step 1: In a 50 mL round-bottom flask at room temperature, 4-(hydroxymethyl)-5α-cholestane-3β,25-diol 13-1 (120 mg, 0.28 mmol) was dissolved in 1,2-dichloroethane (5 mL), and triethylamine (170 mg, 1.68 mmol), 4-dimethylaminopyridine (34 mg, 0.28 mmol) and p-toluenesulfonyl chloride (107 mg, 0.56 mmol) were added at room temperature, followed by stirring at 50°C for 8 hours. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, the mixture was quenched with water (30 mL), extracted with ethyl acetate (20 mL×3), the organic phase was washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain white solid 4-methylbenzenesulfonic acid-[(1R,3aS,3bS,5aS,7S,9aR,9bS,11aR)-7-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methyl ester 33-1 (60 mg, purity: 90 %, yield: 36.36 %). ¹ HNMR(400MHz, CDCl3) δ = 7.80 (d, J=8.2, 2H), 7.34 (d, J=8.1, 2H), 4.33 – 4.22 (m, 1H), 4.19 – 4.11 (m, 1H), 3.79 – 3.71 (m, 1H), 2.45 (s, 3H), 2.15 (d, J=4.7, 1H), 2.04 (s, 1H), 1.94 (d, J=12.4, 1H), 1.84 – 1.24 (m, 22H), 1.21 (s, 6H), 1.13 – 0.93 (m, 6H), 0.90 (d, J=6.4, 3H), 0.61 (s, 6H).

Step 2: 4-Methylbenzenesulfonic acid-[(1R,3aS,3bS,5aS,7S,9aR,9bS,11aR)-7-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methyl ester 33-1 (40 mg, 0.068 mmol) was dissolved in N,N-dimethylformamide (1 mL) at room temperature. Sodium cyanide (20 mg, 0.41 mmol) was added at room temperature. The mixture was stirred at 100 ^° C for 16 hours. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 3:1). After the reaction was completed, the mixture was washed with water (20 The reaction mixture was quenched with 4% paraformaldehyde (20 mL) and extracted with ethyl acetate (10 mL×3). The organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and the organic phase was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain a white solid [(1R, 3aS, 3bS, 5aS, 7S, 9aR, 9bS, 11aR)-7-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]acetonitrile 33 (15.71 mg, purity: 77.49 %, yield: 40.39 %). Compound 33 : ¹ H NMR (400 MHz, CDCl3) δ = 4.97 (s, 1H), 4.56 (s, 1H), 3.92 (dd, J=11.4, 5.2, 1H), 1.95 – 1.88 (m, 2H), 1.81 – 1.24 (m, 23H), 1.14 (s, 6H), 1.08– 0.93 (m, 6H), 0.85 (d, J=6.5, 3H), 0.62 (s, 3H), 0.58 (s, 3H). ¹³ C NMR (101 MHz, CDCl3) δ = 153.33, 102.36, 73.37, 71.13, 56.28, 56.23, 54.49, 49.90, 44.42, 42.62, 40.08, 38.62, 37.27, 36.43, 35.76, 35.26,33.05, 31.61, 29.36, 29.21, 28.28, 24.27, 24.21, 21.72, 20.78, 18.64, 12.94, 12.07. LC-MS: [M+H-2H ₂ O] ⁺ =408.3 Example 34 Preparation of Compound 34 24,24 -difluoro -5α- cholest -3β,4β,25- triol .

Step 1: Dissolve (5R)-5-[(1R,3aS,3bS,7S,9aR, 9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9, 9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2,2-difluorohexanoic acid ethyl ester 24-3 (300 mg, 0.606 mmol, 1 eq) in chloroform (10 mL). Add selenium dioxide (201.8 mg, 1.82 mmol, 3 eq) and N-methylmorpholine (153.2 mg, 1.52 mmol, 2.5 eq) to the solution and stir at room temperature for 20 hours. After the reaction was completed, 30 mL of water was added and the mixture was extracted with ethyl acetate (30 mL*3). The obtained organic phase was dried over anhydrous sodium sulfate and then rotary dried to obtain a crude product. The crude product was purified by silica gel column (petroleum ether: ethyl acetate = 10:1) to obtain (5R)-5-[(1R, 3aS, 3bS, 6R, 7S, 9aR, 9bS, 11aR)-7-acetyloxy-6-hydroxy-9a, 11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2,2-difluorohexanoic acid ethyl ester 34-1 (155 mg, 0.304 mmol, yield: 50%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.70 (d, J = 3.4 Hz, 1H), 4.72 (dt, J = 12.1, 4.0 Hz, 1H), 4.36 – 4.30 (m, 2H), 4.25 (d, J = 2.7 Hz, 1H), 2.10 (s, 3H), 2.04 – 1.92 (m, 3H), 1.89 – 1.83 (m, 2H), 1.72 – 1.64 (m, 2H), 1.57 (dd, J = 10.2, 4.9 Hz, 4H), 1.49 – 1.43 (m, 3H), 1.36 (d, J = 7.1 Hz, 3H), 1.27 (dd, J = 9.3, 2.5 Hz, 2H), 1.22 (s, 3H), 1.17 – 1.09 (m, 3H), 1.07 – 0.99 (m, 2H), 0.94 (d, J = 6.5 Hz, 3H), 0.87 (dd, J = 19.1, 8.6 Hz, 1H), 0.70 (d, J = 12.6 Hz, 3H).

Step 2: (5R)-5-[(1R,3aS,3bS,6R,7S,9aR, 9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6, 7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2,2-difluorohexanoic acid ethyl ester 34-1 (155 mg, 0.304 mmol, 1 eq) was dissolved in ethyl acetate (15 mL), and then platinum dioxide (50%) (75 mg) was added thereto. The mixture was stirred at room temperature for 12 hours. After the reaction was completed, it was filtered. The organic solvent was then rotary dried to obtain the product (5R)-5-[(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2,2-difluorohexanoic acid ethyl ester 34-2 (70 mg, 0.137 mmol, yield: 46%) as an oily compound. ¹ H NMR (400 MHz, cdcl ₃ ) δ 4.69 – 4.61 (m, 1H), 4.25 (q, J = 7.1 Hz, 2H), 3.76 (s, 1H), 2.02 (s, 3H), 1.89 – 1.76 (m, 3H), 1.72 – 1.66 (m, 3H), 1.59 (dd, J = 12.6, 3.7 Hz, 1H), 1.46 (dd, J = 32.8, 19.9 Hz, 5H), 1.28 (s, 3H), 1.16 (dd, J = 22.6, 9.6 Hz, 3H), 1.08 – 1.01 (m, 3H), 0.98 (s, 3H), 0.96 – 0.87 (m, 2H), 0.85 (d, J = 6.6 Hz, 3H), 0.81 (d, J = 4.7 Hz, 1H), 0.58 (s, 3H), 0.54 (d, J = 3.0 Hz, 1H).

Step 3: Dissolve compound (5R)-5-[(1R,3aS,3bS,5aR,6R, 7S,9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2,2-difluorohexanoic acid ethyl ester 34-2 (70 mg, 0.137 mmol, 1 eq) in tetrahydrofuran (5 mL). After replacing nitrogen, methylmagnesium bromide (2.4 M, 0.6 mL, 10 eq) was slowly added dropwise. Stir at room temperature for 3 hours and monitor by TLC (petroleum ether:ethyl acetate = 1:1). After the reaction is completed, water is added to destroy the reaction mixture, and then the mixture is extracted with ethyl acetate (50 mL). The organic phase was washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and rotary dried to obtain a crude product, which was then purified by silica gel separation (petroleum ether: ethyl acetate = 1:1) to obtain (1R, 3aS, 3bR, 7S, 9aS, 9bS, 11aR)-4,4-difluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 34 (11 mg, 0.024 mmol, yield: 18%). Compound 34 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.67 (s, 1H), 3.54 – 3.44 (m, 1H), 1.94 – 1.85 (m, 2H), 1.79 – 1.52 (m, 16H), 1.43 – 1.30 (m, 5H), 1.23 (s, 6H), 1.07 – 0.98(m, 4H), 0.95 (s, 3H), 0.91 (d, J = 6.1 Hz, 2H), 0.85 (d, J = 6.6 Hz, 3H), 0.81 (s, 1H), 0.59 (s, 3H), 0.56 – 0.49 (m, 1H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 74.84, 73.69, 72.30, 64.38, 59.40, 59.37, 58.07, 56.53, 55.82, 48.83, 42.65, 42.63, 39.88, 36.88, 35.50, 35.40, 35.38,34.55, 28.09, 25.86, 24.18, 23.60, 20.59, 18.78, 18.48, 14.67, 12.09. Example 41 & 65 Compound 41 (1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-4,4 -difluoro -9a, 11a -dimethyl -1-[(2R)-7,7,7- trifluoro -6- hydroxyhept -2 - yl ] hexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -6,7- diol Compound 65 Preparation of (1R,3aR,5aR,6R,7S,9aR,9bR,11aR)-4- fluoro -9a,11a -dimethyl -1-[(2R)-7,7,7- trifluoro -6- hydroxyhept -2- yl ]-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a- tetradecahydro -1H- cyclopenta [1,2-a] phenanthrene -6,7- diol .

Step 1: (5R)-5-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6, 7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]hexanal I and (5R)-5-[(3aS,5aR,5bR,7aR,8R,10aR,12bR)-11-fluoro-2,2,5a,7a-tetramethyl A mixture of 4,5,5a,5b,6,7,7a,8,9,10,10a,12,12a,12b-tetradecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[8-yl]hexanal II (70 mg, 0.150 mmol, 1.0 eq) was dissolved in tetrahydrofuran (5 mL). After complete dissolution, cesium fluoride (11.39 mg, 0.075 mmol, 0.5 eq) and (trifluoromethyl)trimethylsilane (106.7 mg, 0.750 mmol, 5 eq) were added to the reaction system in sequence. After the addition was completed, the atmosphere was replaced with nitrogen three times and stirred at room temperature for 1 hour. After the reaction was complete as monitored by TLC (petroleum ether: ethyl acetate = 5:1), tetrabutylammonium fluoride (1 mL, 1 mmol, 1 mol/L) was added. After the addition was completed, the nitrogen atmosphere was replaced three times and stirred at room temperature for 1 hour. After the reaction was complete as monitored by TLC (petroleum ether: ethyl acetate = 5:1), the mixture was extracted with water (10 mL), the reaction solution was washed three times with water (~10 mL), dried over anhydrous sodium sulfate, and concentrated to obtain a crude product. The crude product was purified by flash chromatography (petroleum ether: ethyl acetate = 95:5 to 85:15) to obtain a white solid (6R)-6-[(3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b, 11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]-1,1,1-trifluoroheptan-2-ol 41-1 and (6R)-1,1,1-trifluoro-6-[(3aS,5aR,5bR,7aR,8R,10aR,12aR,12bR)-11-fluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a, 12,12a,12b-tetradecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[8-yl]heptan-2-ol 65-1 mixture (50 mg, purity 80.0%, yield 59.62% based on 41-1 ). Compound 41-1 : ¹ HNMR (400MHz, CDCl ₃ ) δ 3.94 (dt, J = 8.3, 6.2Hz, 2H), 2.11 – 1.95 (m, 1H), 1.93 – 1.85 (m, 2H), 1.83 – 1.71 (m, 4H), 1.66 – 1.50 (m, 6H),1.49 – 1.43 (m, 5H), 1.41 – 1.27 (m, 5H), 1.23 (d, J = 3.4Hz, 3H), 1.19 (dd, J = 9.0, 5.3Hz, 2H), 1.05 (dd,J = 10.5, 7.0Hz, 2H), 1.01 (s, 3H), 0.98 – 0.90 (m, 1H), 0.87 (t, J = 5.8Hz, 3H), 0.82 (dd,J = 13.7, 3.1Hz, 1H), 0.60 (d, J = 12.1Hz, 3H).

Step 2: The raw materials (6R)-6-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]-1,1,1-trifluoroheptan-2-ol 41-1 and (6R)-1,1,1-trifluoro-6-[(3aS,5aR,5bR,7aR, 8R,10aR,12aR,12bR)-11-fluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6, 7,7a,8,9,10,10a,12,12a,12b-tetradecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[8-yl]heptan-2-ol 65-1 mixture (50 mg, 0.093 mmol, 1.0 eq) was dissolved in tetrahydrofuran (5 mL), hydrochloric acid (1 mL, 3 mol/L) was slowly added dropwise, nitrogen was replaced three times, and the mixture was stirred at room temperature for 1 hr. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 1:1). The reaction solution was washed with saturated sodium bicarbonate solution (3×5 mL). The combined organic phases were washed with saturated brine (10 mL), then dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified by flash chromatography (petroleum ether: ethyl acetate = 90:10 to 80:20) to obtain (1R, 3aS, 3bS, 5aR,6R,7S,9aR,9bS,11aR)-4,4-difluoro-9a,11a-dimethyl-1-[(2R)-7,7,7-trifluoro-6-hydroxyhept-2-yl]hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6,7-diol 41 and (1R,3aR,5aR,6R,7S,9aR,9bR,11aR)-4-fluoro-9a,11a-dimethyl-1-[(2R)-7,7,7-trifluoro-6-hydroxyhept-2-yl]-2,3,3a,5,5a,6, A mixture of 7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a] phenanthrene -6,7-diol (40 mg, yield 69.16% based on 41 ) was directly used for the next step.

Step 3: Compounds (1R,3aS,3bS,5aR,6R,7S,9aR, 9bS,11aR)-4,4-difluoro-9a,11a-dimethyl-1-[(2R)-7,7,7-trifluoro-6-hydroxyhept-2-yl]hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6,7-diol 41 and (1R,3aR,5aR,6R,7S,9aR,9bR,11aR)-4-fluoro-9a,11a-dimethyl-1-[(2R)-7,7,7-trifluoro-6-hydroxyhept-2-yl]-2,3,3a,5,5a,6,7,8,9,9a,9b, A mixture of 10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene- 6,7 -diol (23 mg, 0.046 mmol, 1.0 eq) was added to a reaction bottle containing dichloromethane (2 mL), and triethylamine (0.045 mL, 0.324 mmol, 7.0 eq) and benzoyl chloride (0.027 mL, 0.232 mmol, 5.0 eq) were added, and the mixture was stirred at room temperature (20°C) for 18 hr; the reaction was monitored by TLC (dichloromethane: methanol = 20:1). Water (20 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL*2). The organic phases were combined, washed with water (20 mL*2), dried over anhydrous sodium sulfate, filtered, and the filtrate was dried under reduced pressure by rotary drying (water pump, 45°C) to obtain a crude product, which was separated and purified by prep-TLC (dichloromethane: methanol = 20:1) and SFC separation (instrument: Waters Acquity UPCC; chromatography column: Daicel CHIRALPAK ID_3, 3.0*150 mm, 3 um; mobile phase: A/B: CO ₂ /MeOH (0.1% DEA) = 75/25; flow rate: 2.0 ml/min; column temperature: 37 degrees) to give the product 41-2- benzoic acid-(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-4,4-difluoro-6-hydroxy-9a,11a-dimethyl-1-[(2R)-7,7,7-trifluoro-6-hydroxyhept-2-yl]hexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester (20 mg, 0.030 mmol, 64.70%, retention time t _R = 1.096 min) as a white solid. Product 65-2 : Benzoic acid-(1R,3aR,5aR,6R,7S,9aR,9bR,11aR)-4-fluoro-6-hydroxy-9a,11a-dimethyl-1-[(2R)-7,7,7-trifluoro-6-hydroxyhept-2-yl]-2,3,3a,5,5a,6,7,8,9, 9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester (10 mg, 0.010 mmol, 22.38%, retention time t _R = 1.280 min) was a white solid. Compound 41-2 : ¹ H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 7.6 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 5.61 – 5.48 (m, 1H), 3.73 (s, 1H), 3.59 (d, J = 10.7 Hz,1H), 2.28 – 2.13 (m, 1H), 2.12 – 2.07 (m, 1H), 1.94 (m, 1H), 1.88 (m, 1H), 1.83 (m, 2H), 1.80 (m, 3H), 1.75 – 1.69 (m, 2H), 1.69 – 1.63 (m, 1H), 1.56 (m, 1H),1.46 (m, 3H), 1.40 – 1.34 (m, 3H), 1.33 – 1.29 (m, 2H), 1.21 (m, 1H), 1.13 – 1.06 (m, 2H), 1.05 (s, 3H), 0.98 (m, 2H), 0.87 (d, J = 6.4 Hz, 3H), 0.64 (s, 3H). ¹⁹ F NMR (377 MHz, CDCl3) δ -76.92, -77.02, -88.65, -89.28, -110.63, -111.26. Compound 65-2 : ¹⁹ F NMR (377 MHz, CDCl3) δ -76.91, -77.04, -109.74.

Step 4: Compound benzoic acid-(1R,3aS,3bS,5aR,6R,7S, 9aR,9bS,11aR)-4,4-difluoro-6-hydroxy-9a,11a-dimethyl-1-[(2R)-7,7,7-trifluoro-6-hydroxyhept-2-yl]hexahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 41-2 (20 mg, 0.033 mmol, 1.0 eq) was added to a reaction bottle containing methanol (0.5 mL) and tetrahydrofuran (1 mL), and a solution of lithium hydroxide (13.97 mg, 0.333 mmol) in water (0.5 mL) was added, and the mixture was heated to 40°C and stirred for 2 hours. hr; TLC (petroleum ether: ethyl acetate = 1:1) monitoring the reaction showed that the starting material disappeared and a main spot with increased polarity was generated; water (20 mL) was added to the reaction solution, extracted with ethyl acetate (20 mL*3), the organic phases were combined, washed with water (20 mL*2), dried over anhydrous sodium sulfate, filtered, and the filtrate was dried under reduced pressure (water pump, 45°C) to obtain a crude product, which was purified by column chromatography (lithium The product was separated and purified by ethyl acetate (1:0-2:1) to obtain (1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-4,4-difluoro-9a,11a-dimethyl-1-[(2R)-7,7,7-trifluoro-6-hydroxyhept-2-yl]hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6,7-diol 41 (16.40 mg, 0.033 mmol, 99.21%) as a white solid. Compound 41 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.91 (m, 1H), 3.74 (s, 1H), 3.60 (dt, J = 11.3, 4.1 Hz, 1H), 2.21 (m, 1H), 1.98 (m, 2H), 1.86 (m, 3H), 1.81 – 1.75 (m, 2H), 1.74 – 1.71 (m, 1H), 1.70 – 1.62 (m, 3H), 1.57 (m, 2H), 1.46 (m, 3H), 1.41 – 1.37 (m, 2H), 1.35 – 1.28 (m, 2H), 1.25 (m, 1H), 1.11 (m, 2H), 1.06 (s, 3H), 1.04 – 0.95 (m, 2H), 0.93 (d, J = 6.5 Hz, 3H), 0.67 (s, 3H). ¹⁹ F NMR (377 MHz, CDCl ₃ ) δ -80.03, -88.64, -89.27, -110.64, -111.26. ¹⁹ F NMR (377 MHz, CDCl3) δ -76.92, -77.02, -88.65, -89.28, -110.63, -111.26.

Compound benzoic acid-(1R,3aS,3bS,5aR,6R,7S,9aR, 9bS,11aR)-4-fluoro-6-hydroxy-9a,11a-dimethyl-1-[(2R)-7,7,7-trifluoro-6-hydroxyhept-2-yl]hexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 65-2 (10 mg, 0.017 mmol, 1.0 eq) was added to a reaction bottle containing methanol (0.5 mL) and tetrahydrofuran (1 mL), and lithium hydroxide (7.20 mg, 0.172 mmol) and water (0.5 mL) solution, heated to 40°C and stirred for 2 hr; the reaction was monitored by TLC (petroleum ether:ethyl acetate = 1:1); water (20 mL) was added to the reaction solution, and ethyl acetate (20 The mixture was extracted with 1% ethyl acetate (20 mL*3), the organic phases were combined, washed with water (20 mL*2), dried over anhydrous sodium sulfate, filtered, and the filtrate was dried under reduced pressure by rotary drying (water pump, 45°C) to obtain a crude product, which was separated and purified by column chromatography (petroleum ether: ethyl acetate = 1:0-2:1) to obtain the product (1R, 3aR, 5aR, 6R, 7S, 9aR, 9bR, 11aR)-4-fluoro-9a, 11a-dimethyl-1-[(2R)-7,7,7-trifluoro-6-hydroxyhept-2-yl]-2,3,3a, 5,5a, 6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6,7-diol 65 (1.89 mg, 0.004 mmol, 21.44%) as a white solid. Compound 65 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.91 (s, 1H), 3.85 (s, 1H), 3.59 (d, J = 11.0 Hz, 1H), 2.66 (t, J = 12.5 Hz, 1H), 2.07 – 1.98 (m, 2H), 1.94 (d, J = 16.5 Hz, 2H),1.88 – 1.82 (m, 3H), 1.80 – 1.71 (m, 3H), 1.68 (m, 1H), 1.63 – 1.59 (m, 3H), 1.55 (m, 2H), 1.48 (m, 2H), 1.45 (m, 3H), 1.13 (m, 4H), 1.05 (s, 3H), 0.94 (d, J= 6.5 Hz, 3H), 0.65 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -80.03, -109.71. ¹⁹ F NMR (377 MHz, CDCl ₃ ) δ -76.91, -77.04, -109.74. Example 53 Preparation of Compound 53 4-(1- hydroxyethyl )-5α -cholestane -3β,25- diol

Step 1: In a 50 mL round-bottom flask at room temperature, 3β-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-25-hydroxy-5α-cholestane-4-carboxaldehyde 23-3 (23 mg, 0.042 mmol) was dissolved in anhydrous tetrahydrofuran (1.5 mL). The reaction mixture was cooled to 0 ^o C under nitrogen protection, and 3 mol/L methylmagnesium bromide tetrahydrofuran solution (0.07 mL, 0.021 mmol) was added dropwise. The mixture was then stirred at room temperature for 2 hours and monitored by TLC (petroleum ether: ethyl acetate = 4:1). After the reaction was completed, the system was cooled to 0 ^o C and quenched with saturated ammonium chloride aqueous solution (20 mL). The mixture was extracted with ethyl acetate (10 mL×3). The organic phase was saturated with brine (20 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain a white solid 3β-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4-(1-hydroxyethyl)-5α-cholest-25-ol 53-1 (17 mg, purity: 90%, yield: 64.64%). ¹ HNMR (400MHz, CDCl3) δ = 4.20- 4.11(m, 1H), 3.85 – 3.70 (m, 1H), 2.04 – 1.65 (m, 7H), 1.60 – 1.46 (m, 6H), 1.39 – 1.29 (m, 5H), 1.21 (s, 6H), 0.94 (s, 3H), 0.91 (dd, J=6.9, 4.1, 12H), 0.64 (s, 3H), 0.06 (s, 6H).

Step 2: In a 50 mL round-bottom flask, 3β-{[dimethyl(2-methylpropan-2-yl)silyl]oxy}-4-(1-hydroxyethyl)-5α-cholest-25-ol 53-1 (17 mg, 0.03 mmol) was dissolved in 1 mol tetrabutylammonium fluoride tetrahydrofuran solution (0.5 mL) at room temperature and stirred at room temperature for 2 hours. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 1: 1). After the reaction was completed, the system was cooled to 0 ^° C and quenched with saturated aqueous ammonium chloride solution (10 mL), extracted with ethyl acetate (5 mL×3), and the organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1: 1) to obtain white solid 4-(1-hydroxyethyl)-5α-cholestan-3β,25-diol 53 (5.09 mg, purity: 95.12%, yield: 35.73%). Compound 53: ¹ H NMR (400 MHz, CDCl3) δ = 4.19 – 4.08 (m, 1H), 3.83 – 3.71 (m, 1H), 1.96 – 1.65 (m, 7H), 1.56 – 1.47 (m, 5H), 1.42 – 1.17 (m, 18H), 1.14 (s, 6H), 1.07 – 0.92 (m, 5H), 0.88 (s, 3H), 0.84 (d, J=6.5, 3H), 0.57 (s, 3H). ¹³ C NMR (101 MHz, CDCl3) δ = 104.61, 103.05, 101.06, 71.13, 69.23, 56.48, 56.37, 56.18, 44.43, 42.48, 39.95, 38.55, 36.44, 35.88, 35.75, 35.73, 33.64, 33.59, 31.45, 30.97, 30.36, 29.37, 29.21, 29.04, 28.26, 26.29, 25.61, 24.80, 24.27, 21.07, 20.99, 20.92, 20.78, 18.64, 14.96, 12.01. LC-MS: [M+H-2H ₂ O] ⁺ =413.55 Example 55 Preparation of Compound 55 4- bromo -5α -cholestane -3β,25- diol

First step In a 100 mL round-bottom flask, (5R)-5-[(1R,3aS,3bS,6R,7S,9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-8 (500 mg, 1.09 mmol) was dissolved in ethyl acetate (30 mL), 10% palladium carbon (250 mg) and acetic acid (0.3 mL) were added at room temperature, and the mixture was stirred in a hydrogen atmosphere at room temperature for 5 hours. The reaction was monitored by TLC (ethyl acetate/petroleum ether = 8:1). After the reaction was completed, the reaction solution was diluted with ethyl acetate (60 mL), filtered through diatomaceous earth, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 8: 1) to obtain white solid (5R)-5-[(1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-7-acetyloxy-6-hydroxy-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 55-1 (390 mg, purity: 90%, yield: 62.72%). ¹ H NMR (400 MHz, CDCl3) δ 4.75 – 4.69 (m, 1H), 3.83 (s, 1H), 3.66 (s, 3H), 2.35 – 2.20 (m, 2H), 2.08 (s, 3H), 2.03 – 1.05 (m, 27H), 1.05 (s, 3H), 0.92 (d, J = 6.5 Hz, 3H), 0.64 (s, 3H).

Step 2: In a 50 mL round-bottom flask at room temperature, (5R)-5-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 55-1 (250 mg, 0.54 mmol) was dissolved in 1,2-dichloroethane (10 mL). A solution of triphenylphosphine (142 mg, 0.54 mmol) in 1,2-dichloroethane (0.6 mL) was added at 0°C. The reaction mixture was stirred at room temperature for 10 minutes. Carbon tetrabromide (180 mg, 0.54 mmol) in 1,2-dichloroethane (0.9 mL) was added to the reaction mixture at 0°C. The reaction solution was then warmed to room temperature and stirred at 50°C for 16 hours. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 5:1). After the reaction was completed, the reaction mixture was quenched with water (30 mL), extracted with ethyl acetate (20 mL×3), the organic phase was washed with saturated brine (40 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain white solid (5R)-5-[(1R, 3aS, 3bS, 5aR, 7S, 9aR, 9bS, 11aR)-7-acetyloxy-6-bromo-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 55-2 (150 mg, purity: 90%, yield: 47.57%). ¹ H NMR (400 MHz, CDCl3) δ = 4.97 (s, 1H), 4.32 (s, 1H), 3.67 (s, 3H), 2.34 – 2.18 (m, 3H), 2.05 (s, 3H), 1.97 (dd, J=8.0, 4.4, 2H), 1.89 – 1.36 (m, 19H), 1.18 – 1.03 (m, 5H), 0.98 (s, 3H), 0.92 (d, J=6.5, 3H), 0.64 (s, 3H).

Step 3: Dissolve the reactant (5R)-5-[(1R,3aS,3bS,5aR, 6R,7S,9aR,9bS,11aR)-7-acetyloxy-6-bromo-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 55-2 (150 mg, 0.337 mmol, 1 eq) in tetrahydrofuran (10 mL), and replace the reaction system with nitrogen atmosphere. After cooling the reaction system to 0 ^o C, methylmagnesium chloride (1.124 mL, 3.373 mmol, 1 mol/L) was slowly added and stirred at room temperature for 1 h. Monitor the reaction by TLC (petroleum ether:ethyl acetate = 5:1). 20 mL of water was added to the reaction system, and ethyl acetate (25 mL×3) was used for extraction. The organic phase was collected and dried over anhydrous sodium sulfate. The organic phase was vacuum-rotated to obtain a crude product. The crude product was dissolved in ethyl acetate and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 88:12) to obtain 4-bromo-5α-cholestane-3β,25-diol 55 (16 mg, purity: 90.51%, yield: 10.66%). Compound 55 : ¹ H NMR (400 MHz, cdcl3) δ 4.37 (d, J = 2.6 Hz, 1H), 3.87 (s, 1H), 2.41 – 2.30 (m, 1H), 2.00 – 1.94 (m, 1H), 1.87 – 1.73 (m, 4H), 1.64 (dd, J = 12.9, 4.0 Hz, 1H), 1.54 (dd, J = 9.0, 3.4 Hz, 6H), 1.49 – 1.34 (m, 9H), 1.22 (s, 6H), 1.17 – 1.04 (m, 4H), 1.02 (s, 3H), 0.99 – 0.95 (m, 1H), 0.92 (d, J = 6.5 Hz, 3H), 0.87 – 0.72 (m, 2H), 0.65 (s, 3H). Example 56 Preparation of Compound 56 4β-[( ethoxymethyl ) oxy ]-3- methyl -5α- cholestane -3,25- diol .

Step 1: Dissolve (1R,7S,9aR,11aR)-6-hydroxy-1-[(2R)-6-methoxy-6-oxyylidenehexan-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate 55-1 (100 mg, 0.216 mmol) in N,N-diisopropylethylamine (5 mL), add [(chloromethyl)oxy]ethane (204.21 mg, 2.16 mmol), reacted at 130°C for 1.5h, monitored by TLC (petroleum ether: ethyl acetate = 5:1) and NMR, no starting material remained, washed with ethyl acetate and water, dried and concentrated with anhydrous sodium sulfate, and purified by column chromatography (petroleum ether: ethyl acetate = 100: 1~20: 1) to obtain acetic acid-(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-6-[(ethoxymethyl)oxy]-1-[(2R)-6-methoxy-6-oxyylidenehex-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 56-1 (60 mg, 49.04%) as a white solid. ¹ HNMR(399 MHz, Chloroform-d) δ 4.71 – 4.60 (m, 3H), 3.70 (d, J = 8.7 Hz, 1H), 3.65 (s, 3H), 2.23 (tq, J = 16.8, 9.6, 9.1 Hz, 2H), 2.03 (s, 3H), 1.91 (t, J = 12.5 Hz, 2H), 1.53 (s, 3H), 1.39 – 1.30 (m, 4H), 1.26 (d, J = 14.6 Hz, 2H), 1.17 (d, J = 7.3 Hz, 3H), 1.13 (s, 1H), 1.10 – 1.01 (m, 4H), 0.99 (s, 4H), 0.90 (d, J = 6.6 Hz, 3H), 0.62 (s, 3H).

Step 2: Dissolve (1R,3aS,3bS,5aR,6R,7S, 9aR,9bS,11aR)-6-[(ethoxymethyl)oxy]-1-[(2R)-6-methoxy-6-oxyylidenehexan-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate 56-1 (60 mg, 0.115 mmol) in methanol (5 mL), add potassium carbonate (158.70 mg, 1.150 mmol) at room temperature, and stir at room temperature for 5 minutes. h, monitored by TLC (petroleum ether: ethyl acetate = 5:1); after the reaction was completed, water and ethyl acetate were added for extraction, the organic phase was separated and the crude product was dried, and purified by column chromatography (petroleum ether: ethyl acetate = 60:1~3:1) to obtain (5R)-5-[(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-6-[(ethoxymethyl)oxy]-7-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 56-2 (40 mg, 58.89%) as a white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 4.80 (d, J = 6.7 Hz, 1H), 4.53 (d, J = 6.7 Hz, 1H), 3.76 (dq, J = 9.5, 7.1 Hz, 1H), 3.65 (s, 3H), 3.60 – 3.49 (m, 2H), 3.39 (s, 1H), 2.31 – 2.19 (m, 2H), 1.96 – 1.90 (m, 1H), 1.68(s, 2H), 1.57 – 1.44 (m, 2H), 1.42 – 1.32 (m, 3H), 1.31 – 1.25 (m, 2H), 1.22 (t, J = 7.1 Hz, 5H), 1.14 (d, J = 9.5 Hz, 1H), 1.11 – 1.02 (m, 4H), 1.01 – 0.95 (m, 1H), 0.93 (s, 3H), 0.90 (d, J = 6.6 Hz, 3H), 0.62 (s, 3H).

Step 3: Dissolve (5R)-5-[(1R,3aS,3bS,5aR,6R,7S, 9aR,9bS,11aR)-6-[(ethoxymethyl)oxy]-7-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 56-2 (20 mg, 0.042 mmol) in dichloromethane (5 mL), add N-methylphenoline oxide (7.34 mg, 0.063 mmol) and tetrapropylammonium perruthenate (1.47 mg, 0.004 mmol) at room temperature, and stir at room temperature for 1 hr. h, monitored by TLC (petroleum ether: ethyl acetate = 5:1); after the reaction was completed, the product was filtered through diatomaceous earth, the filtrate was concentrated, and purified by column chromatography (petroleum ether: ethyl acetate = 60:1~3:1) to obtain (5R)-5-[(1R,3aS,3bS,5aR,6R,9aR,9bS,11aR)-6-[(ethoxymethyl)oxy]-9a,11a-dimethyl-7-oxyylidenehexahydro-1H-cyclopenta[1,2-a]phenanthren-1-yl]hexanoic acid methyl ester 56-3 (15 mg, 0.029 mmol, 69.08%) as a white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 4.65 – 4.52 (m, 2H), 3.65 (s, 3H), 3.60 – 3.48 (m, 3H), 2.29 – 2.13 (m, 3H), 1.37 (d,J = 19.8 Hz, 7H), 1.24 (s, 2H), 1.18 (d,J = 4.7 Hz, 3H), 1.15 (d,J =7.3 Hz, 3H), 1.11 – 1.03 (m, 3H), 0.96 (s, 1H), 0.90 (d,J = 6.6 Hz, 3H), 0.65 (s, 4H).

Step 4: Dissolve (5R)-5-[(1R,3aS,3bS,5aR,6R,9aR, 9bS,11aR)-6-[(ethoxymethyl)oxy]-9a,11a-dimethyl-7-oxo-1-hexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 56-3 (20 mg, 0.042 mmol) in tetrahydrofuran (3 mL), add methyl lithium (9.22 mg, 0.42 mmol) dropwise under nitrogen protection at zero degree, stir at room temperature for 2 h, and monitor by TLC (petroleum ether: ethyl acetate = 2:1); after the reaction is completed, add water and ethyl acetate for extraction, separate the organic phase, dry the crude product, and purify it by column chromatography (petroleum ether: ethyl acetate = 50:1~1:1) After purification, 4β-[(ethoxymethyl)oxy]-3-methyl-5α-cholestane-3,25-diol 56 (10 mg, 0.019 mmol, 45.90%) was obtained as a white solid. Compound 56 : ¹ H NMR (400 MHz, Chloroform-d) δ 4.78 (d,J = 6.6 Hz, 1H), 4.60 (d,J = 6.6 Hz, 1H), 3.73 – 3.57 (m, 2H), 3.15 (s, 1H), 1.94 (d,J = 12.6 Hz, 1H), 1.74 (t,J = 14.7 Hz, 3H),1.65 (m, 2H),1.53-1.61 (m, 5H), 1.43(d,J = 15.2 Hz, 3H), 1.36 (d,J = 10.6 Hz, 3H), 1.29 (d,J = 22.8 Hz, 3H), 1.23 (s, 3H), 1.22 – 1.16 (m, 12H), 1.12 – 1.05 (m, 2H), 1.01 (dd,J = 19.5, 8.8 Hz, 3H), 0.94 (s, 3H), 0.89 (d,J = 6.5 Hz, 3H), 0.62 (s, 3H). ¹³ CNMR (101 MHz, Chloroform-d) δ 98.16, 90.81, 71.10, 70.96, 64.32, 56.48, 56.12, 47.42, 44.37, 42.57, 39.86, 36.13, 35.73, 35.47, 32.89 , 32.31 , 29.18 , 28.23 , 26.75 , 24.55 , 24.18 , 20.75 ,18.60 , 15.09 , 12.02 . ELSD-MS: [Ms+NH ₄ ] ⁺ = 491.42; [Ms-H ₂ O-OH] ⁺ = 493.42. HPLC: 94.97% (CAD). Example 59 Compound 59 Preparation of 3- methyl -5α- cholestane -4β,3,25- triol .

4β-[(Ethoxymethyl)oxy]-3-methyl-5α-cholestane-3,25-diol 56 (50 mg, 0.101 mmol) was dissolved in tetrahydrofuran (3 mL), p-toluenesulfonic acid (174.08 mg, 1.014 mmol) was added at room temperature, and the mixture was heated to 40°C and stirred for 1 h. TLC (petroleum ether: ethyl acetate = 1:1) was used for monitoring. After the reaction was completed, water and ethyl acetate were added for extraction. The organic phase was separated, and the crude product was dried over anhydrous sodium sulfate. It was purified by column chromatography (petroleum ether: ethyl acetate = 50:1~1:1) to obtain 3-methyl-5α-cholestane-4β,3,25-triol 59 (20 mg, 0.044 mmol, 45.35%) as a white solid. Compound 59 : ¹ H NMR (399 MHz, Chloroform-d) δ 3.32 (s, 1H), 2.18 (s, 1H), 1.94 (d, J = 12.8 Hz, 1H), 1.63 (s, 1H), 1.76 (s, 3H), 1.53 (s, 4H), 1.42 (d, J = 13.9 Hz, 3H), 1.39 – 1.32 (m, 5H), 1.31 (s, 3H), 1.23 (s,3H), 1.19 (s, 6H), 1.04 (dd, J = 11.3, 6.8 Hz, 4H), 1.00 (s, 3H), 0.89 (d, J = 6.5 Hz, 3H), 0.62 (s, 3H). ¹³ C NMR (100 MHz, Chloroform-d) δ 72.14 , 71.09 , 56.54 , 56.13 , 55.50 , 46.96 , 44.38 , 42.58 , 39.86 , 36.39 , 36.23 , 35.78 , 35.72 , 35.45 , 32.41 , 31.57 , 29.34 , 29.17 , 28.23 , 26.06 , 24.80 , 24.18 ,20.74 , 20.54 , 18.61 , 14.64 , 12.05. ELSD-MS: [Ms+NH ₄ ] ⁺ = 433.38; [Ms-H ₂ O-OH] ⁺ = 435.38. HPLC: 93.78% (CAD). Example 60 Compound 60 Preparation of 24- fluoro -5α - cholest -3β,4β,25- triol .

Step 1: Weigh (1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-6-hydroxy-1-[(2R)-6-methoxy-6-oxyylidenehexan-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1, 2-i]phenanthrene-7-yl acetate IV-1 (300 mg, 0.65 mol, 1.0 eq.) and dissolve it in anhydrous methanol (5 mL). Add potassium carbonate (897 mg, 6.5 mmol), then heat the temperature to 25°C and stir for 16 hours. Monitor by TLC (petroleum ether: ethyl acetate = 2:1) until the reaction is complete. The reaction solution was filtered and concentrated, and the crude product was purified by column chromatography (petroleum ether: ethyl acetate = 0-50%) to obtain (5R)-5-[(1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-6,7-dihydroxy-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1, 2-a]phenanthrene-1-yl]hexanoic acid methyl ester IV-2 (210 mg, 76.9%) as a white solid. 1H NMR (399 MHz, Chloroform-d) δ 3.71 (d, J = 3.1 Hz, 1H), 3.65 (s, 3H), 3.53 (dt, J = 11.3, 4.4 Hz, 1H), 2.33 – 2.18 (m, 2H), 1.97 – 1.84 (m, 2H), 1.83 – 1.60 (m, 8H), 1.42 – 1.28 (m, 5H), 1.28 – 1.15 (m, 3H), 1.11 – 1.01 (m, 4H), 1.00 (s, 3H), 0.90 (d, J = 6.5 Hz, 4H), 0.62 (s, 3H), 0.57 (td, J = 11.4, 4.2 Hz, 1H).

Step 2: Weigh (5R)-5-[(1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-6,7-dihydroxy-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1, 2-a]phenanthrene-1-yl]hexanoic acid methyl ester IV-2 (250 mg, 0.59 mmol) and dissolve it in acetone (20 mL). Add 4A molecular sieve (250 mg) and p-toluenesulfonic acid (203 mg, 1.18 mmol) and stir at room temperature. Monitor by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction is completed, the insoluble matter is removed by filtration, and the filtrate is concentrated and purified by column chromatography (petroleum ether: ethyl acetate = 0-30%) to obtain (5R)-5-[(3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12aR, 12bR)-2, 2, 5a, 7a-tetramethyl-4, 5, 5a, 5b, 6, 7, 7a, 8, 9, 10, 10a, 10b, 11, 12, 12a, 12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7, 8-d][1, 3]Dioxadiazol-8-yl]hexanoic acid methyl ester IV-3 (220 mg, 0.48 mmol, 81.3%) white solid. ¹ H NMR (399 MHz, Chloroform-d) δ 3.97 (dt, J = 8.8, 5.7 Hz, 2H), 3.65 (s, 3H), 2.25 (ddd, J = 10.5, 8.5, 6.7 Hz, 2H), 1.97 – 1.90 (m, 1H), 1.76 (td, J = 11.5, 6.6 Hz, 3H), 1.71 – 1.63 (m, 3H), 1.58 – 1.52 (m, 1H), 1.49 (s, 4H), 1.47 – 1.32 (m, 6H), 1.28 (s, 3H), 1.23 (ddd, J = 14.1, 8.9, 5.6 Hz, 3H), 1.08 (td, J = 10.7, 9.2, 3.7 Hz, 3H), 1.02 (s, 3H), 0.98 – 0.93 (m, 1H), 0.90 (d, J = 6.4 Hz, 3H), 0.86 – 0.80 (m, 2H), 0.64 (s, 3H), 0.61 – 0.54 (m, 1H).

Step 3: In a three-necked flask, (5R)-5-[(3aS,5aR,5bS, 7aR,8R,10aS,10bS,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6, 7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]hexanoic acid methyl ester IV-3 (370 mg, 0.803 mmol, 1.0 eq.) was dissolved in tetrahydrofuran (7 mL), and trimethylsilyl chloride (0.440 mL, 2.409 mmol, 3.0 eq.) was added. Replace the three-necked flask with nitrogen atmosphere, then cool to -78°C and add lithium diisopropylamide (172.08 mg, 1.606 mmol, 2.0 eq.). The reaction solution is then heated to 0°C and stirred for 15 minutes. Add a tetrahydrofuran (1 mL) solution of N-fluorobisbenzenesulfonamide (506.50 mg, 1.606 mmol, 2.0 eq.). The reaction solution is heated to room temperature and stirred for 1 hour. Monitor by TLC (petroleum ether: ethyl acetate = 10:1). When the raw materials are completely reacted, add water to the reaction solution to quench. The obtained mixed solution was extracted three times with ethyl acetate, and the combined organic phases were washed once with brine, dried over anhydrous sodium sulfate, and concentrated to obtain a crude product, which was purified by column chromatography (ethyl acetate/petroleum ether = 0-20%) to obtain (5R)-5-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9, 10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]-2-fluorohexanoic acid methyl ester as a white solid 60-1 (200 mg, 49.42%). ¹ H NMR (399 MHz, Chloroform-d) δ4.14 (ddd, J=48.5, 18.2, 10.2 Hz, 1H), 3.71 (d, J=3.0 Hz, 1H), 3.53 (dt, J=11.4, 4.3 Hz, 1H), 1.94 (dt, J=12.5, 3.5 Hz, 1H), 1.82 (dd, J=9.0, 5.3 Hz, 2H), 1.76–1.71 (m,3H), 1.70–1.62 (m, 3H), 1.59–1.46 (m, 2H), 1.37 (ddd, J=19.3, 12.0, 4.8 Hz, 4H), 1.30–1.21 (m, 3H), 1.19 (d, J=5.0 Hz, 6H), 1.13–1.02 (m, 4H), 0.99 (s, 3H), 0.94 (dd, J=8.7, 4.3 Hz, 2H), 0.90 (dd, J=6.5, 2.0Hz, 3H), 0.87–0.79 (m, 1H), 0.63 (s, 3H), 0.57 (td, J=11.4, 4.2 Hz, 1H). LC-MS: [M-HF] ⁺ =458.45;

Step 4 : (5R)-5-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12aR,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7, 7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-2-fluorohexanoic acid methyl ester 60-1 (100 mg, 0.209 mmol, 1 eq.) was dissolved in tetrahydrofuran (5 mL). The mixture was cooled to 0°C under nitrogen atmosphere and methyl lithium (0.653 mL, 1.045 mmol, 5.0 eq.) was added. The mixture was heated to room temperature and stirred for 1 hour. The mixture was monitored by TLC (petroleum ether: ethyl acetate = 10:1). After the reaction was complete, a small amount of water was added to quench the reaction. The mixture was directly concentrated to obtain a crude product, which was purified by column chromatography (ethyl acetate/petroleum ether = 0-30%) to obtain (6R)-6-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-3-fluoro-2-methylheptan-2-ol as a white solid 60-2 (75 mg, 71.24%). ¹ H NMR (399 MHz, Chloroform-d) δ 4.14 (ddd, J = 48.4, 18.5, 10.3 Hz, 1H), 4.01 – 3.92 (m, 2H), 1.94 (d, J = 12.2 Hz, 1H), 1.79 (s, 2H), 1.64 (dd, J = 15.6, 12.1 Hz, 4H), 1.54 (s, 5H), 1.49 (s, 3H), 1.44 (d, J = 14.1 Hz, 6H), 1.28 (s, 3H), 1.24 (d, J = 11.6 Hz, 3H), 1.19 (d, J = 4.9 Hz, 6H), 1.07 (d, J = 11.1 Hz, 4H), 1.02 (s, 3H), 0.97 (s, 1H), 0.92 – 0.88 (m, 3H), 0.87 – 0.79 (m, 2H), 0.65 (s, 3H), 0.58 (t, J = 10.2 Hz, 1H).

Step 5 : (6R)-6-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8, 9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-3-fluoro-2-methylheptan-2-ol 60-2 (75 mg, 0.157 mmol) was dissolved in tetrahydrofuran (5 mL), and hydrochloric acid (2 mL, 4.000 mmol, 25.5 eq.) was added. Stir at room temperature for 1 hour. Monitor by TLC (petroleum ether: ethyl acetate = 5:1). Dilute the reaction solution with water, extract with ethyl acetate three times, combine the organic phases, wash once with brine, and dry over anhydrous sodium sulfate. Concentrate to obtain a crude product, and purify by column chromatography (ethyl acetate/petroleum ether = 0-60%) to obtain 24-fluoro-5α-cholestane-3β,4β,25-triol as a white solid 60 (40 mg, 0.087 mmol, 55.29%). Compound 60 : ¹ H NMR (399 MHz, Chloroform-d) δ4.14 (ddd, J=48.5, 18.2, 10.2 Hz, 1H), 3.71 (d, J=3.0 Hz, 1H), 3.53 (dt, J=11.4, 4.3 Hz, 1H), 1.94 (dt, J=12.5, 3.5 Hz, 1H), 1.82 (dd, J=9.0, 5.3 Hz, 2H), 1.76–1.71 (m,3H), 1.70–1.62 (m, 3H), 1.59–1.46 (m, 2H), 1.37 (ddd, J=19.3, 12.0, 4.8 Hz, 4H), δ 0.17–0.16 (m, 1H), 0.14 (d, J=5.0 Hz, 6H), 0.13–0.19 (m, 4H), 0.99 (s, 3H), 0.94 (dd, J=8.7, 4.3 Hz, 2H), 0.90 (dd, J=6.5, 2.0Hz, 3H), 0.87–0.79 (m, 1H), 0.63 (s, 3H), 0.57 (td, J=11.4, 4.2 Hz, 1H). LC-MS: [M+Na]+=461.45. Preparation of Example 61 Compound 61, 3,25- dihydroxy - 3- methyl -5α- cholest -4- one .

3-Methyl-5α-cholestane-4β,3,25-triol 59 (20 mg, 0.046 mmol) was dissolved in dichloromethane (3 mL), and N-methylmorpholine oxide (8.08 mg, 0.069 mmol) and tetrapropylammonium perruthenate (1.61 mg, 0.005 mmol) were added at room temperature. The mixture was stirred for 1 h at room temperature and monitored by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction, the mixture was filtered through diatomaceous earth, and the filtrate was concentrated and purified by column chromatography (petroleum ether: ethyl acetate = 50:1~1:1) to obtain 3,25-dihydroxy-3-methyl-5α-cholestane-4-one 61 (10 mg, 0.020 mmol, 85.85%) as a white solid. Compound 61: ¹ H NMR (399 MHz, Chloroform-d) δ 2.33 – 2.37 (m, 1H),2.07 – 1.96 (m, 2H), 1.85 – 1.71 (m, 4H), 1.46 – 1.40 (m, 4H), 1.38 (s, 3H), 1.37 – 1.31 (m, 3H), 1.24 (d, J = 12.6 Hz, 5H), 1.19 (s, 6H), 1.17 –1.10 (m, 2H), 1.10 – 1.04 (m, 2H), 1.01 (d, J = 8.9 Hz, 2H), 0.97 – 0.93 (m, 1H), 0.90 (d, J = 6.5 Hz, 3H), 0.80 (dt, J = 13.1, 8.9 Hz, 1H), 0.69 (s, 3H), 0.63 (s, 3H). ELSD-MS: [M+NH ₄ ] ⁺ = 433.38; [MH ₂ O-OH] ⁺ = 435.38. Example 66 Compound 66 : Preparation of (1R,3aR,7S,9aS,9bR,11aR)-4-fluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol.

Step 1: Dissolve (5R)-5-[(1R,3aS,3bS,7S,9aR, 9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4, 6,7,8,9,9a,9b, 10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-7 (1 g, 2.25 mmol, 1 eq) in tetrahydrofuran (10 mL), add cobalt acetate (80 mg, 0.45 mmol, 0.2 eq), N-hydroxyphenylenediamine (0.15 g, 0.90 mmol, 0.4 eq), tert-butyl peroxide (1.01 g, 11.25 mmol, 1 eq) to the solution. mmol, 5 eq), and stirred at room temperature for 20 hours. After the reaction was completed, 30 mL of water was added and the mixture was extracted with ethyl acetate (30 mL*3). The obtained organic phase was dried over anhydrous sodium sulfate and then rotary dried to obtain a crude product. The crude product was purified by passing through a silica gel column (petroleum ether/ethyl acetate = 10/1) to obtain (5R)-5-[(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-4-oxyylidene-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 66-1 (0.6 g, 1.31 mmol, yield: 58%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.70 (d, J = 1.5 Hz, 1H), 4.80 – 4.64 (m, 1H), 3.67 (s, 3H), 2.48 (dddd, J = 15.6, 12.1, 9.1, 2.4 Hz, 3H), 2.25 (ddd, J = 22.3, 12.9, 5.3 Hz, 3H), 2.05 (s, 3H), 2.01 – 1.95 (m, 2H), 1.93 – 1.84 (m, 1H), 1.79 – 1.65 (m, 2H), 1.65 – 1.46 (m, 5H), 1.40 (ddd, J = 11.6, 8.9, 4.3 Hz, 2H), 1.28 (ddd, J = 10.9, 10.5, 5.9 Hz, 3H), 1.21 (s, 3H), 1.18 – 1.05 (m, 3H), 0.94 (d, J = 6.5 Hz, 3H), 0.68 (s, 3H).

Step 2: Dissolve compound (5R)-5-[(1R,3aS,3bS, 7S,9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-4-oxyylidene-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 66-1 (0.6 g, 1.31 mmol, 1 eq) in ethyl acetate (15 mL), then add palladium carbon (10%) (120 mg) and stir at room temperature for 12 hours. After the reaction is completed, filter and The organic solvent was then rotary dried to obtain the product (5R)-5-[(1R,3aS,3bR,7S,9aS,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-4-oxyylidenehexahydro-1H-cyclopenta[1,2-a]phenanthren-1-yl]hexanoic acid methyl ester 66-2 (450 mg, 0.977 mmol, yield: 75%) as an oily compound. ¹ H NMR (400 MHz, cdcl ₃ ) δ 5.36 – 5.24 (m, 1H), 4.30 (s, 3H), 3.00 – 2.81 (m, 5H), 2.70 – 2.58 (m, 5H), 2.55 – 2.47 (m, 2H), 2.42 (dt, J = 13.4, 3.5 Hz, 1H), 2.35 – 2.26 (m, 2H), 2.22 – 2.10 (m, 6H), 2.09 – 1.99 (m, 3H), 1.86 (d, J = 12.4 Hz, 1H), 1.76 (s, 1H), 1.73 (s, 1H), 1.73 (s, 3H), 1.70 (s, 1H), 1.69 (d, J = 3.3 Hz, 1H), 1.67 – 1.60 (m, 1H), 1.56 (d, J = 6.5 Hz, 3H), 1.28 (s, 3H).

Step 3: Dissolve compound (5R)-5-[(1R,3aS,3bR,7S, 9aS,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-4-oxyylidene hexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 66-2 (150 mg, 0.326 mmol, 1.0 eq) and DAST (157 mg, 0.977 mmol, 3 eq) in tetrahydrofuran (5 mL), stir at 80°C for 3 hours, and detect by TLC. After the reaction is completed, water is added to destroy the reaction, and then extracted with ethyl acetate (50 mL). The organic phase is washed twice with saturated brine, dried with anhydrous sodium sulfate, filtered, The crude product was dried by rotary evaporation and purified by silica gel separation (petroleum ether: ethyl acetate = 1:1) to obtain (R)-5-((3S, 5R, 9R, 10S, 13R, 14R, 17R)-3-acetyloxy-7-fluoro-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,1 A mixture of methyl 7-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-yl)hexanoate 66-3 and methyl (R)-5-((3S,5R,8R,9S,10S,13R,14S,17R)-3-acetyloxy-7,7-difluoro-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)hexanoate 66-3′ (70 mg, 0.145 mmol, yield based on 66-3′: 45%). Compound 66-3': ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.75 – 4.63 (m, 1H), 3.66 (s, 3H), 2.34 – 2.22 (m, 2H), 2.10 – 1.91 (m, 5H), 1.84 (ddd, J = 9.3, 7.6, 3.7 Hz, 3H), 1.78 – 1.65 (m, 5H), 1.57 – 1.49 (m, 3H), 1.45 – 1.22 (m, 7H), 1.09 (ddd, J = 28.8, 14.4, 9.4 Hz, 5H), 0.94 (t, J = 5.4 Hz, 3H), 0.85 (d, J = 11.0 Hz, 3H), 0.71 – 0.62 (m, 3H).

Step 4: A mixture of (R)-5-((3S, 5R, 9R, 10S, 13R, 14R, 17R)-3-acetyloxy-7-fluoro-10,13-dimethyl-2,3,4,5,6,9,10, 11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-yl)hexanoic acid methyl ester 66-3 and (R)-5-((3S, 5R, 8R, 9S, 10S, 13R, 14S, 17R)-3-acetyloxy-7,7-difluoro-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)hexanoic acid methyl ester 66-3′ (70 mg, 0.145 mmol, 1 eq) was dissolved in tetrahydrofuran (5 mL), and after replacing nitrogen, methylmagnesium bromide (2.4M) (0.6 mL, 10 eq) was slowly added dropwise, stirred at room temperature for 3 hours, and detected by TLC. After the reaction was completed, water was added to destroy it, and then extracted with ethyl acetate (50 mL). The organic phase was washed twice with saturated brine, and the organic phase was dried over anhydrous sodium sulfate, filtered, and rotary dried to obtain a crude product. Then, it was purified by silica gel separation (petroleum ether: ethyl acetate = 1:1) to obtain (3S, 5R, 9R, 10S, 13R, 14R, 17R)-7-fluoro-17-((R)-6-hydroxy-6-methylheptane-2-yl)-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16, A mixture of 17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3-ol 66-4 and (3S,5R,8R,9S,10S,13R,14S,17R)-7,7-difluoro-17-((R)-6-hydroxy-6-methylheptane-2-yl)-10,13-dimethylhexahydro-1H-cyclopenta[a]phenanthrene-3-ol 66-4' (22 mg, 0.05 mmol, yield based on 66-4': 34%) was directly used in the next step.

Step 5: A mixture of (3S, 5R, 9R, 10S, 13R, 14R, 17R)-7-fluoro-17-((R)-6-hydroxy-6-methylheptane-2-yl)-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopentadien[a]phenanthrene-3-ol 66-4 and (3S, 5R, 8R, 9S, 10S, 13R, 14S, 17R)-7,7-difluoro-17-((R)-6-hydroxy-6-methylheptane-2-yl)-10,13-dimethylhexahydro-1H-cyclopenta[a]phenanthrene-3-ol 66-4' (1.3 g, 2.95 mmol, 1 eq) was dissolved in dichloromethane (25 mL), triethylamine (1.19 g, 11.80 mmol, 4 eq) was slowly added dropwise, DMAP (0.29 g, 2.36 mmol, 0.8 eq) was added, and benzoyl chloride (1.04 g, 7.38 mmol, 2.5 eq) was slowly added dropwise at room temperature, stirred for 1 hour at room temperature, and detected by TLC. After the reaction was completed, water was added to destroy it, and then extracted with ethyl acetate (50 mL), the organic phase was washed twice with saturated brine, the organic phase was dried over anhydrous sodium sulfate, filtered, and rotary dried to obtain a crude product, which was then separated and purified by silica gel (petroleum ether: ethyl acetate = 1:1) to obtain a mixture of 66-5 and 66-5' (1.5 g, 2.82 mmol, yield: 95%). After SFC separation (instrument: Waters Acquity UPCC; column: Daicel CHIRALPAK OZ3, 3*150mm, 3um; mobile phase: A/B: CO2/MeOH (0.1% DEA) = 70/30; flow rate: 2.0 ml/min; column temperature: 37 degrees), (6R)-6-[(1R, 3aS, 3bR, 7S, 9aS, 9bS, 11aR)-7-(benzyloxy)-4,4-difluoro-9a, 11a-dimethylhexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylheptan-2-ol 66-5' (1 g, retention time t _R =1.178 min) and (1R,3aR,7S,9aS,9bR,11aR)-4-fluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 66-5 (200 mg, retention time t _R =1.601 min). Compound 66-5 : ¹ H NMR (400MHz, CDCl ₃ ) δ 8.07 – 7.99 (m, 2H), 7.55 (t, J = 7.4Hz, 1H), 7.43 (t, J = 7.6Hz, 2H), 4.96 (d, J = 5.0Hz, 1H), 1.22 (s, 6H),0.96 – 0.85 (m, 6H), 0.72 – 0.64 (m, 3H). ¹⁹ F NMR (377 MHz, CDCl3) δ -110.61. Compound 66-5' : ¹⁹ F NMR (377 MHz, CDCl3) δ -88.95, -89.58, -110.84, -111.47.

Step 6: Dissolve compound (1R,3aR,7S,9aS,9bR,11aR)-4-fluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,5,5a, 6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 66-5 (100 mg, 0.2 mmol, 1 eq) in tetrahydrofuran (4 mL) and methanol (2 ml), add lithium hydroxide monohydrate (82 mg, 2 mmol, 10 eq), stir at 40 degrees for 3 hours, detect by TLC, add water to destroy the reaction after completion, and then extract with ethyl acetate (50 mL). The organic phase was washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and rotary dried to obtain a crude product, which was then purified by silica gel separation (petroleum ether: ethyl acetate = 1:1) to obtain (1R, 3aR, 7S, 9aS, 9bR, 11aR)-4-fluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethyl-2,3,3a, 5,5a, 6,7,8,9,9a, 9b, 10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 66 (70 mg, 0.16 mmol, yield: 85%). Compound 66 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.60 (t, J = 4.4 Hz, 1H), 2.08 – 1.90 (m, 3H), 1.83 (dddd, J = 19.8, 15.3, 9.9, 5.8 Hz, 6H), 1.63 (s, 1H), 1.56 – 1.38 (m, 10H), 1.35 –1.25 (m, 3H), 1.22 (s, 6H), 1.18 – 1.03 (m, 4H), 0.94 (d, J = 6.5 Hz, 3H), 0.82 (s, 3H), 0.64 (s, 3H). Example 79 Compound 79 Preparation of (1R,3aR,5aR,7S,9aR,9bR,11aR)-4- fluoro -7- hydroxy -1-[(2R)-6- hydroxy -6- methylhept -2- yl ]-9a,11a - dimethyl -2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a- tetradecahydro -1H- cyclopenta [1,2-a] phenanthrene -6 -one .

Step 1 : Dissolve (5R)-5-[(1R,3aS,3bS,6R,7S,9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-8 (1 g, 2.17 mmol) in anhydrous tetrahydrofuran (20 mL) in a 100 mL round-bottom flask at room temperature. The reaction mixture was cooled to 0 ^° C under nitrogen protection. Methylmagnesium bromide (7.23 mL, 21.70 mmol), then stirred at room temperature for 2 hours, and the reaction was monitored by TLC (petroleum ether: ethyl acetate = 2: 1). After the reaction was completed, the system was cooled to 0 ^o C, quenched with saturated aqueous ammonium chloride solution (60 mL), extracted with ethyl acetate (50 mL×3), the organic phase was washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2: 1) to obtain white solid cholester-6(5)-ene-3β,4β,25-triol 79-1 (800 mg, purity: 90%, yield: 79.38%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.68 (d, J = 3.3 Hz, 1H), 4.14 (s, 1H), 3.56 (d, J = 11.1 Hz, 1H), 2.22 – 1.72 (m, 7H), 1.72 – 1.31 (m, 13H), 1.21 (s, 6H), 1.18 (s, 3H), 1.15 – 1.00 (m, 5H), 0.93 (d, J = 6.5 Hz, 3H), 0.68 (s, 3H).

Step 2: Cholester-6(5)-ene-3β,4β,25-triol 79-1 (400 mg, 0.96 mmol) was dissolved in tetrahydrofuran (15 mL) in a 100 mL round-bottom flask at room temperature. Triethylamine (2.9 g, 28.8 mmol), 4-dimethylaminopyridine (117 mg, 0.96 mmol) and acetic anhydride (980 mg, 9.6 mmol) were added at room temperature. The mixture was stirred at 80°C for 24 hours and monitored by TLC (petroleum ether:ethyl acetate = 10:1). After the reaction was completed, the mixture was quenched with water (50 mL) and extracted with ethyl acetate (30 mL×3). The organic phase was saturated with brine (50 mL×4). The reaction mixture was washed with 4% paraformaldehyde (2% ethyl acetate) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 10:1) to obtain white solid (6R)-6-[(1R,3aS,3bS,6R,7S,9aR,9bS,11aR)-6,7-diethoxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylhept-2-yl acetate 79-2 (415 mg, purity: 90%, yield: 71.76%). ¹ H NMR (400 MHz, CDCl3) δ = 5.84 – 5.79 (m, 1H), 5.50 (d, J=2.5, 1H), 4.74 (dt, J=7.8, 4.1, 1H), 2.07 (s, 3H), 2.05 – 2.02 (m, 1H), 2.01 (s, 3H), 1.97 (s, 3H), 1.93 – 1.54 (m, 10H), 1.54 – 1.44 (m, 3H), 1.42 (s, 6H), 1.39 – 1.15 (m, 7H), 1.13 (s, 3H), 1.10 – 0.96 (m, 4H), 0.92 (d, J=6.5, 3H), 0.67 (s, 3H).

Step 3: In a 100 mL round-bottom flask at room temperature, (6R)-6-[(1R,3aS,3bS,6R,7S,9aR,9bS,11aR)-6,7-diethoxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylhept-2-yl acetate 79-2 (400 mg, 0.73 mmol) was dissolved in acetone (15 mL). N-Hydroxyphthalimide (24 mg, 0.15 mmol), cobalt acetate (13 mg, 0.073 mmol) were added at room temperature. mmol) and tert-butyl hydroperoxide (265 mg, 2.94 mmol), then stirred at room temperature for 36 hours, the reaction was monitored by TLC (petroleum ether: ethyl acetate = 10:1), after the reaction was completed, quenched with water (50 mL), extracted with ethyl acetate (40 mL×3), the organic phase was washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain white solid acetic acid-(6R)-6-[(1R,3aS,3bS,6R,7S,9aR, 9bS,11aR)-6,7-diacetyloxy-9a,11a-dimethyl-4-oxoylide-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylhept-2-yl ester 79-3 (300 mg, purity: 90%, yield: 65.81%). ¹ H NMR (400 MHz, CDCl3) δ 5.92 (s, 1H), 5.61 (d, J = 2.3 Hz, 1H), 4.80 (dt, J = 7.8, 4.2 Hz, 1H), 2.34 (dt, J = 22.4, 9.8 Hz, 2H), 2.10 (s, 3H), 2.03(s, 3H), 1.97 (s, 3H), 1.92 – 1.52 (m, 10H), 1.42 (s, 6H), 1.39 – 1.34 (m, 2H), 1.32 (s, 3H), 1.29 – 1.00 (m, 8H), 0.93 (d, J = 6.5 Hz, 3H), 0.68 (s, 3H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 202.20, 170.06, 169.47, 158.31, 131.14, 73.61, 71.51, 71.12, 54.68, 50.80, 49.91, 45.95, 44.37, 43.06, 38.53, 37.93, 36.42, 35.80, 35.69, 29.31, 29.27, 28.52, 26.20, 22.21, 21.15, 20.99, 20.78, 18.83, 17.91, 11.92.

Step 4 In a 50 mL round-bottom flask at room temperature, (6R)-6-[(1R,3aS,3bS,6R,7S,9aR,9bS,11aR)-6,7-diethoxy-9a,11a-dimethyl-4-oxyylidene-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthren-1-yl]-2-methylhept-2-yl acetate 79-3 (300 mg, 0.54 mmol) was dissolved in ethyl acetate (10 mL) and tetrahydrofuran (10 mL). 10% Pd/C (150 mg) was added at room temperature, and the mixture was stirred in hydrogen atmosphere at room temperature for 1 hour. The reaction was monitored by TLC (ethyl acetate/petroleum ether = 15:1). After the reaction was completed, the reaction solution was diluted with ethyl acetate (20 mL), filtered through diatomaceous earth, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 15:1) to obtain white solid acetate-(6R)-6-[(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-6,7-diethoxy-9a,11a-dimethyl-4-oxyylidene hexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylhept-2-yl ester 79-4 (200 mg, purity: 90%, yield: 59.60%). ¹ H NMR (400 MHz, CDCl3) δ 5.17 (s, 1H), 4.83 – 4.74 (m, 1H), 2.58 – 2.46 (m, 1H), 2.37 – 2.28 (m, 1H), 2.25 – 2.17 (m, 1H), 2.11 (s, 3H), 2.07 – 2.02 (m,1H), 1.97 (d, J = 4.3 Hz, 6H), 1.94 – 1.81 (m, 3H), 1.80 – 1.46 (m, 9H), 1.40 – 1.31 (m, 5H), 1.28 (s, 3H), 1.26 (s, 6H), 1.16 – 1.01 (m, 5H), 0.91 (d, J = 6.5Hz, 3H), 0.64 (s, 3H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ = 210.87, 170.51, 170.19, 82.52, 72.07, 71.97, 55.16, 54.96, 49.99, 48.91, 48.58, 42.77, 42.53, 41.15, 38.50, 36.17, 35.78, 35.52, 31.93, 29.70, 28.38, 26.05, 25.06, 22.69, 22.51, 21.13, 20.97, 20.91, 20.32, 18.70, 14.12, 13.65, 12.04.

Step 5: In a 50 mL round-bottom flask at room temperature, (6R)-6-[(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-6,7-diacetyloxy-9a,11a-dimethyl-4-oxyylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylhept-2-yl acetate 79-4 (200 mg, 0.36 mmol) was dissolved in diethylaminosulfur trifluoride (3 mL), stirred at 40°C for 6 hours, and the reaction was monitored by TLC (petroleum ether:ethyl acetate = 10:1). After the reaction was completed, the reaction solution was added to ice water (30 mL) to quench, extracted with ethyl acetate (20 mL×3), and the organic phase was saturated with brine (30 mL×4). mL) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain white solid acetic acid-(6R)-6-[(1R,3aS,3bS,5aR,6R,7S,9aR, A mixture of (9bS,11aR)-6,7-diacetyloxy-4,4-difluoro-9a,11a-dimethylhexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylhept-2-yl acetate 79-5A and (6R)-6-[(1R,3aR,5aR,6R,7S,9aR,9bR,11aR)-6,7-diacetyloxy-4-fluoro-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylhept-2-yl acetate 79-5B (120 mg, purity: 90%. Yield calculated based on 79-5A : 51.55%). Compound 79-5A : ¹ H NMR (400 MHz, CDCl3) δ 5.20 (s, 1H), 4.79 (dd, J = 8.3, 4.0 Hz, 1H), 2.10 (s, 3H), 1.97 (d, J = 3.6 Hz, 6H), 1.92 – 1.59 (m , 21H), 1.42 (s,6H), 1.19 – 1.09 (m, 6H), 1.05 (s, 3H), 0.91 (d, J = 6.5 Hz, 3H), 0.66 (s, 3H). ¹³ C NMR (101 MHz, CDCl3) δ 170.25, 82.53, 72.01, 71.84, 55.25, 43.05, 41.15, 39.11, 36.14, 35.61, 29.70, 26.05, 22.67, 22.50, 20.98, 20.92, 20.55,20.36, 18.66, 13.25, 11.83.

Step 6: In a 50 mL round-bottom flask at room temperature, (6R)-6-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-4,4-difluoro-6,7-dihydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylhept-2-yl acetate 79-5A and (6R)-6-[(1R,3aR,5aR,6R,7S,9aR, The mixture 79-5B (385 mg, 0.77 mmol) was dissolved in tetrahydrofuran (5 mL) and methanol (5 mL). Lithium hydroxide monohydrate (324 mg, 7.72 mmol) and water (3 mL) were added at room temperature. The mixture was stirred at 45°C for 16 hours. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 2:1). After the reaction was completed, the mixture was diluted with water (50 mL) and ethyl acetate (40 mL×3) extraction, the organic phase was washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain a white solid (1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-4,4-difluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6,7-diol 79- A mixture of (1R,3aR,5aR,6R,7S,9aR,9bR,11aR)-4-fluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6,7-diol 79-6B (340 mg, purity: 90.18 %, yield based on 79-6A : 86.97 %). Compound 79-6A : ¹ H NMR (400 MHz, CDCl3) δ = 3.74 (s, 1H), 3.63 – 3.57 (m, 1H), 2.32 – 1.72 (m, 15H), 1.57 – 1.25 (m, 14H), 1.21 (s, 6H), 1.06 (s, 3H), 0.93 (d,J=6.5, 3H), 0.67 (s, 3H).

Step 7: In a 50 mL round-bottom flask at room temperature, (1R,3aS,3bS,6R,7S,9aR,9bS,11aR)-4,4-difluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6,7-diol 79-6A and (1R,3aR,5aR,6R,7 A mixture of (S,9aR,9bR,11aR)-4-fluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6,7-diol 79-6B (1.41 g, 3.09 mmol) was dissolved in dichloromethane (30 mL), and triethylamine (0.94 g, 9.26 mmol), 4-dimethylaminopyridine (0.3 g, 2.47 mmol) and benzoyl chloride (0.65 g, 4.63 mmol) were added at room temperature, followed by stirring at room temperature for 20 minutes. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 4:1). After the reaction was completed, it was quenched with water (100 mL), extracted with ethyl acetate (60 mL×3), the organic phase was washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, and the organic phase was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1). The white solid (1.5 g) was obtained and subjected to chiral separation (instrument: Waters Acquity UPCC; column: REGIS CHIRAL (S, S)-whey O1 4.6*150mm, 3.5um; mobile phase: A/B: CO2/MeOH (0.1% DEA) = 50/50; flow rate: 1.5 ml/min; column temperature: 37 degrees) to obtain a white solid (1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-7-(benzyloxy)-4,4-difluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-ol 79-7A (1.04 g, purity: 95%, yield: 58.52%, retention time t _R = 2.597 min) and (1R,3aR,5aR,6R,7S,9aR,9bR, 11aR)-7-(benzyloxy)-4-fluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-ol 79-7B (0.24 g, purity: 95%, yield: 14.02%, retention time t _R = 2.963 min). Compound 79-7A : ¹ H NMR (400 MHz, CDCl3) δ = 8.11 – 7.97 (m, 2H), 7.58 (t, J=7.4, 1H), 7.46 (t, J=7.7, 2H), 4.99 (dt, J=7.3, 3.9, 1H), 3.98 (s, 1H), 2.46 – 1.23 (m,25H), 1.22 (s, 6H), 1.14 (s, 3H), 1.12 – 0.97 (m, 3H), 0.94 (d, J=6.5, 3H), 0.68 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -89.02 (d, J=236.3, 1F), -110.79 (d, J=236.2, 1F). Compound 79-7B : ¹ H NMR (400 MHz, CDCl3) δ = 8.05 (t, J =6.1, 2H), 7.58 (t, J =7.4, 1H), 7.46 (t, J =7.7, 2H), 5.03 – 4.95 (m, 1H), 4.10 (d, J =15.7, 1H), 2.73 (dd, J =16.8, 8.5, 1H), 2.40 – 1.29 (m, 26H), 1.22 (s, 6H), 1.13 (s, 3H), 0.95 (d, J =6.4, 3H), 0.65 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -109.82 (s, 1F).

Step 8 In a 50 mL round-bottom flask at room temperature, (1R,3aR,5aR, 6R,7S,9aR,9bR,11aR)-7-(benzyloxy)-4-fluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a, 9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-ol 79-7B (100 mg, 0.19 mmol) was dissolved in dichloromethane (10 mL). Dess-Martin periodinane (242 mg, 0.57 mmol) was added at room temperature and stirred at room temperature for 2 hours. The reaction was monitored by TLC (ethyl acetate/petroleum ether = 4:1). After the reaction was completed, saturated aqueous sodium sulfite solution (5 mL) and saturated aqueous sodium bicarbonate solution (5 mL) were added to quench the reaction, extracted with dichloromethane (10 mL×3), washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, concentrated the organic phase, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain a white solid (1R,3aR,5aR,7S,9aR,9bR,11aR)-7-(benzyloxy)-4-fluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,5,5a,6, 7,8,9,9a,9b,10,11,11a-Tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-one 79-8 (81 mg, purity: 80 %, yield: 65.05 %). ¹ H NMR (400 MHz, CDCl3) δ = 8.10 (d, J=7.4, 2H), 7.58 (t, J=7.4, 1H), 7.45 (t, J=7.7, 2H), 5.48 – 5.41 (m, 1H), 2.64 – 2.33 (m, 3H), 2.26 – 1.30 (m, 23H), 1.22 (s, 6H), 0.95 (d, J=6.5, 3H), 0.82 (s, 3H), 0.64 (s, 3H). ¹³ C NMR (101 MHz, CDCl3) δ = 203.65, 165.72, 133.24, 129.90, 128.38, 71.12, 54.36, 53.16, 52.49, 48.80, 44.37, 43.60, 41.83, 41.17, 39.43, 36.44, 36.19, 35.61, 29.41, 29.37, 29.22, 28.49, 28.34, 25.12, 25.03, 23.37, 22.28, 20.84, 18.97, 14.97, 12.61. ¹⁹ F NMR (376 MHz, CDCl3) δ = -110.02 (s, 1F).

Step 9 In a 50 mL round-bottom flask at room temperature, (1R,3aR,5aR, 7S,9aR,9bR,11aR)-7-(benzyloxy)-4-fluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a, 9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-one 79-8 (80 mg, 0.15 mmol) was dissolved in tetrahydrofuran (2 mL) and methanol (2 mL). Potassium carbonate (105 mg, 0.76 mmol) and water (1 mL) were added at room temperature. mL), then stirred at room temperature for 4 hours, and the reaction was detected by TLC (petroleum ether: ethyl acetate = 3:1). After the reaction was completed, it was diluted with water (20 mL), extracted with ethyl acetate (10 mL×3), and the organic phase was saturated with brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3: 1) to obtain a white solid (1R, 3aR, 5aR, 7S, 9aR, 9bR, 11aR)-4-fluoro-7-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethyl-2,3,3a, 5,5a, 6,7,8,9,9a,9b, 10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-one 79 (15.55 mg, purity: 100%, yield: 23.47%). Compound 79 : ¹ H NMR (400 MHz, CDCl3) δ = 4.13 (dd, J=17.4, 7.6, 1H), 2.60 – 2.35 (m, 3H), 2.19 – 1.27 (m, 24H), 1.22 (s, 6H), 0.94 (d, J=6.3, 3H), 0.74 (s, 3H), 0.64 (s, 3H). ¹³ C NMR (101 MHz, CDCl3) δ = 210.89, 74.90, 71.11, 54.35, 52.51, 52.30, 52.21, 48.94, 48.87, 44.37, 43.65, 41.71, 39.42, 36.43, 36.17, 35.03, 32.02, 30.13, 29.71, 29.43, 29.21, 28.48, 28.46, 25.10, 25.02, 23.40, 23.10, 22.24, 22.23, 20.82, 18.96, 15.04, 12.60. ¹⁹ F NMR (376 MHz, CDCl3) δ = -110.10 (s, 1F). LC-MS: [M+Na] ⁺ =457.1 Example 85 & 86 Compound 85 or 86 7β-Fluoro-5α-cholestane-3β,25-diol Compound 86 or 85 Preparation of 7α-fluoro-5α-cholestane-3β,25-diol.

In the first step , (5R)-5-[(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b, 10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-7 (1 g, 2.25 mmol, 1 eq) was dissolved in tetrahydrofuran (10 mL). Cobalt acetate (80 mg, 0.45 mmol, 0.2 eq), N-hydroxyphenylenediamine (0.15 g, 0.90 mmol, 0.4 eq), tert-butyl peroxide (1.01 g, 11.25 mmol, 5 eq), stirred at room temperature for 20 hours. After the reaction was completed, 30 mL of water was added, extracted with ethyl acetate (30 mL*3), and the obtained organic phase was dried over anhydrous sodium sulfate and then rotary dried to obtain a crude product, which was purified by silica gel column (petroleum ether/ethyl acetate = 10/1) to obtain (5R)-5-[(1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-7-acetyloxy-9a, 11a-dimethyl-4-oxyylidene-2,3,3a, 3b, 4,6,7,8,9,9a,9b,10, 11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 72-1 (0.6 g, 1.31 mmol, yield: 58%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.70 (d, J = 1.5 Hz, 1H), 4.80 – 4.64 (m, 1H), 3.67 (s, 3H), 2.48 (dddd, J = 15.6, 12.1, 9.1, 2.4 Hz, 3H), 2.25 (ddd, J = 22.3, 12.9, 5.3 Hz, 3H), 2.05 (s, 3H), 2.01 – 1.95 (m, 2H), 1.93 – 1.84 (m, 1H), 1.79 – 1.65 (m, 2H), 1.65 – 1.46 (m, 5H), 1.40 (ddd, J = 11.6, 8.9, 4.3 Hz, 2H), 1.28 (ddd, J = 10.9, 10.5, 5.9 Hz, 3H), 1.21 (s, 3H), 1.18 – 1.05 (m, 3H), 0.94 (d, J = 6.5 Hz, 3H), 0.68 (s, 3H).

In the second step , compound (5R)-5-[(1R,3aS,3bS,7S,9aR, 9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-4-oxyylidene-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthren-1-yl]hexanoic acid methyl ester 72-1 (0.6 g, 1.31 mmol, 1 eq) was dissolved in ethyl acetate (15 mL), and then palladium carbon (10%) (120 mg) was added thereto and stirred at room temperature for 12 hours. After filtration, the organic solvent was rotary dried to obtain the product (5R)-5-[(1R,3aS,3bR,7S,9aS,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-4-oxyylidenehexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 72-2 (450 mg, 0.977 mmol, yield: 75%) as an oily compound. ¹ H NMR (400 MHz, cdcl ₃ ) δ 5.36 – 5.24 (m, 1H), 4.30 (s, 3H), 3.00 – 2.81 (m, 5H), 2.70 – 2.58 (m, 5H), 2.55 – 2.47 (m, 2H), 2.42 (dt, J = 13.4, 3.5 Hz, 1H), 2.35 – 2.26 (m, 2H), 2.22 – 2.10 (m, 6H), 2.09 – 1.99 (m, 3H), 1.86 (d, J = 12.4 Hz, 1H), 1.76 (s, 1H), 1.73 (s, 1H), 1.73 (s, 3H), 1.70 (s, 1H), 1.69 (d, J = 3.3 Hz, 1H), 1.67 – 1.60 (m, 1H), 1.56 (d, J = 6.5 Hz, 3H), 1.28 (s, 3H).

Step 3: Methyl (5R)-5-[(1R,3aS,3bR,5aR,7S,9aS, 9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-4-oxoylidenehexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoate 72-2 (300 mg, 0.65 mmol, 1 eq) was dissolved in methanol (10 mL). Sodium borohydride (30 mg, 0.78 mmol, 1.2 eq) was added to the solution and stirred at room temperature for 1 hour. After the reaction was completed, 30 mL of water was added and extracted with ethyl acetate (30 mL*3). The obtained organic phase was dried over anhydrous sodium sulfate and then rotary dried to obtain a crude product of (5R)-5-[(1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-7-acetyloxy-4-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 85-1 (240 mg, 0.52 mmol, yield: 80%), which was directly used for the next step.

Step 4 Compound (5R)-5-[(1R,3aS,3bR,5aS,7S, 9aS,9bS,11aR)-7-acetyloxy-4-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 85-1 (240 mg, 0.52 mmol, 1 eq) was dissolved in super dry pyridine (5 mL), and then 4-methylbenzenesulfonyl chloride (824 mg, 4.32 mmol, 10 eq) was added thereto. The mixture was stirred at room temperature for 5 days. After the reaction was completed, 30 ml of 3M hydrochloric acid aqueous solution, extracted with ethyl acetate (30mL*3), and then the organic solvent was rotary dried to obtain a crude product. The crude product was separated and purified by silica gel (petroleum ether: ethyl acetate = 10:1) to obtain a product. After SFC separation (instrument: Waters Acquity UPCC; chromatography column: Daicel CHIRALPAK IB 4.6*250mm, 5um; mobile phase: A/B: CO2/MeOH (0.1% DEA) = 60/40; flow rate: 1.5 ml/min; column temperature: 37 degrees), 85-2 (60 mg, 0.1 mmol, yield: 22.5%, retention time _tR = 1.769 min) and 86-1 (70 mg, 0.13 mmol, yield: 30%, retention time _tR = 2.792 min) is an oily compound. Compound 85-2 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.76 (d, J = 8.1 Hz, 1H), 7.31 (d, J = 8.1 Hz, 1H), 4.67 – 4.57 (m, 0H), 4.46 (td, J = 10.4, 5.1 Hz, 0H), 3.67 (s, 3H), 2.44 (s, 3H), 2.26 (dd, J = 15.3, 8.2 Hz, 2H), 2.00 (s, 3H), 1.96 (d, J = 13.0 Hz, 1H), 1.81 (d, J = 15.1 Hz, 3H), 1.73 – 1.63 (m, 4H), 1.53 9 (s, 3H), 1.47 (d, J = 9.6 Hz, 2H), 1.41 – 1.32 (m, 4H), 1.28 – 1.17 (m, 5H), 1.14 – 0.99 (m, 4H), 0.91 (d, J = 6.4 Hz, 3H), 0.81 (s, 3H), 0.76 (s, 1H), 0.62 (s, 3H). Compound 86-1 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.78 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 4.76 (s, 1H), 4.62 – 4.46 (m, 1H), 3.68 (s, 3H), 2.45 (s, 3H), 2.26 (dt, J =15.7, 7.7 Hz, 2H), 2.00 (s, 3H), 1.90 (d, J = 13.0 Hz, 1H), 1.79 (d, J = 13.2 Hz, 1H), 1.69 (d, J = 12.4 Hz, 2H), 1.46 (dd, J = 17.7, 12.2 Hz, 6H), 1.38 (d, J =13.0 Hz, 3H), 1.29 – 1.17 (m, 6H), 1.08 (dt, J = 22.8, 12.9 Hz, 6H), 0.90 (d, J = 6.3 Hz, 3H), 0.77 (s, 3H), 0.60 (s, 3H).

Step 5: Dissolve 85-2 (60 mg, 0.1 mmol, 1.0eq) and TBAF (38 mg, 0.146 mmol, 1.5 eq) in tetrahydrofuran (2 mL), stir at 65°C for 12 hours, and detect by TLC. After the reaction is completed, water is added to destroy the reaction, and then extracted with ethyl acetate (50 mL). The organic phase is washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and rotary dried to obtain a crude product, which is then purified by silica gel separation (petroleum ether: ethyl acetate = 1:1) to obtain 85-3 (20 mg, 0.145 mmol, yield: 44%), which is directly used for the next step.

Step 6: Dissolve 85-3 (20 mg, 0.043 mmol, 1 eq) in tetrahydrofuran (2 mL). After replacing nitrogen, slowly add methylmagnesium bromide (2.4 M) (0.6 mL, 10 eq) dropwise, stir at room temperature for 3 hours, and detect by TLC. After the reaction is completed, add water to destroy it, and then extract it with ethyl acetate (50 mL). The organic phase is washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and rotary dried to obtain a crude product, which is then purified by silica gel separation (petroleum ether: ethyl acetate = 4:1) to obtain 85 (6 mg, 0.014 mmol, yield: 33%). Compound 85 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.63 (d, J = 49.6 Hz, 1H), 3.63 (s, 1H), 1.95 (d, J = 12.6 Hz, 1H), 1.88 – 1.80 (m, 2H), 1.76 – 1.68 (m, 3H), 1.63 (d, J = 13.2Hz, 2H), 1.52 (dd, J = 11.0, 8.1 Hz, 6H), 1.39 (dd, J = 12.3, 9.6 Hz, 7H), 1.29 – 1.25 (m, 4H), 1.21 (s, 6H), 1.10 (ddd, J = 14.2, 10.1, 5.1 Hz, 4H), 0.92 (d, J= 6.5 Hz, 3H), 0.80 (s, 3H), 0.65 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -196.28.

Similar operation is performed by replacing raw material 85-2 with 86-1 to obtain 86 . Compound 86 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.28 – 4.09 (m, 1H), 3.65 – 3.54 (m, 1H), 2.00 (dd, J = 9.4, 3.4 Hz, 1H), 1.86 – 1.70 (m, 5H), 1.59 (d, J = 11.5 Hz, 2H), 1.52 (d, J = 12.9 Hz, 2H), 1.45 (d, J = 10.9 Hz, 4H), 1.35 (dd, J = 12.4, 4.5 Hz, 5H), 1.30 – 1.23 (m, 3H), 1.21 (s, 6H), 1.17 – 1.03 (m, 5H), 0.92 (d, J= 6.5 Hz, 3H), 0.86 (s, 3H), 0.68 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -167.50. Example 94 Preparation of Compound 94 (1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-5,5 -difluoro -6 - hydroxy - 6 -methylhept -2- yl ]-4,4 -difluoro -9a, 11a -dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -6,7- diol

Step 1: Dissolve (R)-5-((3S, 4R, 8S, 9S, 10R, 13R, 14S, 17R)-3-acetyloxy-4-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-yl)-2,2-difluorohexanoic acid ethyl ester 34-1 ( 450 mg, 0.88 mmol) in anhydrous tetrahydrofuran (12 mL) at room temperature. Cool to 0 ^° C under nitrogen protection and add methylmagnesium bromide (3M in 2-Me-THF, 2.9 mL, 8.8 mmol), then stirred at room temperature for 2 hours, and monitored by TLC (petroleum ether: ethyl acetate = 2: 1). After the reaction, the system was cooled to 0 ^° C, quenched with saturated aqueous ammonium chloride solution (30 mL), extracted with ethyl acetate (30 mL × 2), the organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4: 1) to obtain a white solid (3S, 4R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-5,5-difluoro-6-hydroxy-6-methylheptane-2-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11, 12,13,14,15,16,17-Tetradecahydro-1H-cyclopentadienyl[a]phenanthrene-3,4-diol 94-1 (195 mg, purity: 95%, yield: 49%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.68 (d, J = 3.4 Hz, 1H), 4.14 (d, J = 3.4 Hz, 1H), 3.57 (dd, J = 7.7, 4.0 Hz, 1H), 2.14 – 1.94 (m, 4H), 1.94 – 1.79 (m, 4H), 1.74 (d, J = 18.2 Hz, 1H), 1.68 – 1.53 (m, 6H), 1.52 – 1.40 (m, 4H), 1.31 (s, 6H), 1.18 (s, 3H), 1.16 – 1.07 (m, 3H), 1.05 – 0.98 (m, 1H), 0.94 (d, J = 6.6 Hz, 3H), 0.90 – 0.82 (m, 1H), 0.69 (s, 3H).

Step 2: 3S, 4R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-5,5-difluoro-6-hydroxy-6-methylheptane-2-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopentadien[a]phenanthrene-3,4-diol 94-1 (193 mg, 0.42 mmol, 1.0 eq) was dissolved in tetrahydrofuran (10 mL) at room temperature. Triethylamine (6.37 g, 63.0 mmol, 150 eq), 4-dimethylaminopyridine (154 mg, 1.26 mmol, 3.0 eq) and acetic anhydride (2.14 g, 21.0 mmol, 50 eq), followed by stirring at 80°C for 24 h, and the reaction was monitored by TLC (petroleum ether:ethyl acetate = 1:1). After the reaction was completed, the mixture was quenched with ice water (50 mL), extracted with ethyl acetate (30 mL×2), the organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 20:1) to obtain a white solid (3S, 4R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-6-acetyloxy-5,5-difluoro-6-methylheptane-2-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopentadienyl[a]phenanthrene-3,4-diyl diacetate 94-2 (182 mg, purity: 90%, yield: 74.59%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.84 – 5.79 (m, 1H), 5.50 (d, J = 2.6 Hz, 1H), 4.74 (dt, J = 12.4, 4.1 Hz, 1H), 2.15 – 2.08 (m, 1H), 2.07 (s, 3H), 2.03 (s, 3H), 2.01 (s, 3H), 1.97 – 1.65 (m, 6H), 1.60 (s, 6H), 1.48 (d, J = 9.6 Hz, 3H), 1.27 (d, J = 12.1 Hz, 7H), 1.23 – 1.16 (m, 2H), 1.13 (s, 3H), 1.13 – 0.97 (m, 3H), 0.95 (d, J = 6.5 Hz, 3H), 0.88 (dd, J = 13.4, 7.8 Hz, 1H), 0.69 (s, 3H).

Step 3: (3S, 4R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-6-acetyloxy-5,5-difluoro-6-methylheptane-2-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopentadienyl[a]phenanthrene-3,4-diyl diacetate 94-2 (182 mg, 0.31 mmol, 1.0 eq) was dissolved in acetone (8 mL) at room temperature. N-hydroxyphthalidylidene (10 mg, 0.062 mmol, 0.2 eq), cobalt acetate (5.5 mg, 0.031 mmol, 0.1 eq) and tert-butyl hydroperoxide (5 M in hexane, 0.25 mL, 1.24 mmol, 4.0 eq), then stirred at room temperature for 36 hours, monitored by TLC (petroleum ether: ethyl acetate = 10:1), after the reaction was completed, quenched with water (30 mL), extracted with ethyl acetate (20 mL × 2), the organic phase saturated with brine (30 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether:ethyl acetate=15:1) to obtain a white solid (3S,4R,8S,9S,10R,13R,14S,17R)-17-((R)-6-acetyloxy-5,5-difluoro-6-methylheptane-2-yl)-10,13-dimethyl-7-oxy-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,4-diyl diacetate 94-3 (120 mg, purity: 90%, yield: 65.22%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.93 (s, 1H), 5.61 (d, J = 2.7 Hz, 1H), 4.80 (dt, J = 12.2, 4.0 Hz, 1H), 2.43 – 2.26 (m, 2H), 2.09 (d, J = 5.7 Hz, 4H), 2.04 (d, J = 5.4 Hz, 7H), 2.00 – 1.87 (m, 3H), 1.85 – 1.66 (m, 3H), 1.59 (s, 6H), 1.48 (s, 2H), 1.39 – 1.04 (m, 12H), 0.96 (d, J = 6.5 Hz, 3H), 0.70 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -113.92 – -117.67 (m, 2F).

Step 4: (3S, 4R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-6-acetyloxy-5,5-difluoro-6-methylheptane-2-yl)-10,13-dimethyl-7-oxy-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,4-diyl diacetate 94-3 (120 mg, 0.20 mmol) was dissolved in ethyl acetate (3 mL) and tetrahydrofuran (3 mL) at room temperature, 10% Pd/C (60 mg) was added at room temperature, and the mixture was stirred in a hydrogen atmosphere at room temperature for 6 hours. The reaction was monitored by TLC (ethyl acetate/petroleum ether = 1:4). After the reaction was completed, the reaction solution was diluted with ethyl acetate (20 mL), filtered through diatomaceous earth, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 15:1) to obtain a white solid (3S, 4R, 5R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-6-acetyloxy-5,5-difluoro-6-methylheptane-2-yl)-10,13-dimethyl-7-oxohexadecahydro-1H-cyclopentadienyl[a]phenanthrene-3,4-diyl diacetate 94-4 (53 mg, purity: 90%, yield: 44.54%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.17 (s, 1H), 4.78 (dd, J = 12.1, 3.6 Hz, 1H), 2.52 (t, J = 13.5 Hz, 1H), 2.34 (t, J = 11.4 Hz, 1H), 2.27 – 2.18 (m, 1H), 2.12 (s, 3H), 2.10 – 2.05 (m, 1H), 2.03 (s, 3H), 1.98 (s, 3H), 1.96 – 1.82 (m, 4H), 1.71 (t, J = 12.8 Hz, 4H), 1.59 (s, 6H), 1.44 (ddd, J = 18.3, 17.6, 6.7 Hz, 4H), 1.35 – 1.24 (m, 6H), 1.19 – 1.04 (m, 4H), 1.01 – 0.91 (m, 4H), 0.66 (s, 3H).

Step 5: (3S, 4R, 5R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-6-acetyloxy-5,5-difluoro-6-methylheptane-2-yl)-10,13-dimethyl-7-oxohexadecahydro-1H-cyclopentadienyl[a]phenanthrene-3,4-diyl diacetate 94-4 (53 mg, 0.089 mmol) was dissolved in diethylaminosulfur trifluoride (2 mL) at room temperature and stirred at 70°C for 2 hours. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 4:1). After the reaction was completed, the reaction solution was diluted with ethyl acetate and slowly added dropwise to ice water (20 mL) for quenching. The mixture was extracted with ethyl acetate (15 mL×2). The organic phase was saturated with brine (20 mL). mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether:ethyl acetate=10:1) to obtain a white solid (3S,4R,5R,8S,9S,10R,13R,14S,17R)-17-((R)-6-acetyloxy-5,5-difluoro-6-methylheptane-2-yl)-7,7-difluoro-10,13-dimethylhexadecahydro-1H-cyclopentadienyl[a]phenanthrene-3,4-diyl diacetate 94-5 (45 mg, purity: 90%, yield: 81.82%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.21 (s, 1H), 4.83 – 4.76 (m, 1H), 2.10 (s, 3H), 2.03 (s, 3H), 1.98 (s, 3H), 1.83 (dd, J = 14.1, 10.0 Hz, 5H), 1.76 – 1.67 (m, 4H), 1.59 (s, 6H), 1.46 (dd, J = 18.1, 9.1 Hz, 4H), 1.30 (dd, J = 15.2, 7.1 Hz, 4H), 1.14 (d, J = 12.8 Hz, 3H), 1.06 (s, 3H), 0.99 (s, 1H), 0.95 (d, J = 6.5 Hz, 3H), 0.88 (s, 1H), 0.68 (s, 3H). ¹⁹ F NMR (377 MHz, CDCl ₃ ) δ -89.25 (d, J = 238.2 Hz, 1F), -110.61 (d, J = 237.8 Hz, 1F), -114.63 – -116.99 (m, 2F).

Step 6: (3S, 4R, 5R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-6-acetyloxy-5,5-difluoro-6-methylheptane-2-yl)-7,7-difluoro-10,13-dimethylhexadecahydro-1H-cyclopentadienyl[a]phenanthrene-3,4-diyl diacetate 94-5 (45 mg, 0.073 mmol, 1.0 eq) was dissolved in tetrahydrofuran (1 mL) and methanol (1 mL) at room temperature, and lithium hydroxide monohydrate (15 mg, 0.365 mmol, 5.0 eq) and water (0.5 mL) were added at room temperature, followed by stirring at room temperature for 30 min. TLC The reaction was monitored by HPLC (petroleum ether: ethyl acetate = 10:1). After the reaction was completed, the mixture was diluted with water (10 mL), extracted with ethyl acetate (10 mL×2), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain a white solid (3S, 4R, 5R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-5,5-difluoro-6-hydroxy-6-methylheptane-2-yl)-7,7-difluoro-10,13-dimethylhexahydro-1H-cyclopentadienyl[a]phenanthrene-3,4-diol 94-6 ( 28 mg, purity: 90 %, yield: 77.78%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.74 (s, 1H), 3.66 – 3.56 (m, 1H), 2.32 – 2.11 (m, 1H), 1.98 (d, J = 12.5 Hz, 2H), 1.91 – 1.77 (m, 6H), 1.76 – 1.64 (m, 6H), 1.44 (dd, J = 17.3, 4.5 Hz, 5H), 1.30 (s, 6H), 1.12 (dd, J = 17.0, 12.1 Hz, 3H), 1.06 (d, J = 5.4 Hz, 3H), 1.00 (d, J = 4.0 Hz, 1H), 0.94 (d, J = 6.5 Hz, 3H), 0.90 – 0.83 (m, 1H), 0.68 (s, 3H).

Step 7: (3S, 4R, 5R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-5,5-difluoro-6-hydroxy-6-methylheptane-2-yl)-7,7-difluoro-10,13-dimethylhexadecahydro-1H-cyclopentadien[a]phenanthrene-3,4-diol 94-6 (28 mg, 0.057 mmol, 1.0 eq) was dissolved in dichloromethane (2 mL) and tetrahydrofuran (1 mL) at room temperature, and triethylamine (35 mg, 0.34 mmol, 6.0 eq), 4-dimethylaminopyridine (7 mg, 0.057 mmol, 1.0 eq) and benzoyl chloride (24 mg, 0.17 mmol, 3.0 eq), then stirred at room temperature for 8 hours, the reaction was monitored by TLC (petroleum ether: ethyl acetate = 1:1), after the reaction was completed, quenched with water (10 mL), extracted with ethyl acetate (10 mL×2), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) and separated by SFC (instrument: Waters Acquity UPCC; chromatography column: Daicel CHIRALPAK IB 4.6*250mm, 5um; mobile phase: A/B: CO2/MeOH (0.1% DEA) = 60/40; flow rate: 1.5 mL/min; Column temperature: 37 degrees) to give a white solid (3S, 4R, 5R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-5,5-difluoro-6-hydroxy-6-methylheptane-2-yl)-7,7-difluoro-4-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopentyl[a]phenanthrene-3-ylbenzoate 94-7 (15 mg, purity: 95%, yield: 44.12%, retention time t _R = 1.225 min). ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.04 (d, J = 7.3 Hz, 2H), 7.58 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 4.99 (d, J = 12.0 Hz, 1H), 3.99 (s, 1H), 2.37 – 2.16 (m, 1H), 2.15 – 1.96 (m, 3H), 1.83 (d, J = 9.5 Hz, 7H), 1.76 (s, 3H), 1.51 – 1.42 (m, 3H), 1.32 (s, 3H), 1.31 (s, 6H), 1.14 (s, 2H), 1.14 (s, 3H), 1.03 (s, 2H), 0.94 (d, J = 6.5 Hz, 3H), 0.69 (s, 3H).

Step 8: (3S, 4R, 5R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-5,5-difluoro-6-hydroxy-6-methylheptane-2-yl)-7,7-difluoro-4-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopentyl[a]phenanthrene-3-ylbenzoate 94-7 (15 mg, 0.025 mmol, 1.0 eq) was dissolved in tetrahydrofuran (0.5 mL) and methanol (0.5 mL) at room temperature, and lithium hydroxide monohydrate (11 mg, 0.25 mmol, 10.0 eq) and water (0.2 mL) were added at room temperature, followed by stirring at room temperature for 30 min. TLC The reaction was monitored by HPLC (petroleum ether: ethyl acetate = 10:1). After the reaction was completed, the mixture was diluted with water (10 mL), extracted with ethyl acetate (10 mL×2), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain a white solid (3S, 4R, 5R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-5,5-difluoro-6-hydroxy-6-methylheptane-2-yl)-7,7-difluoro-10,13-dimethylhexahydro-1H-cyclopentadienyl[a]phenanthrene-3,4-diol 94 (6.23 mg, purity: 100 %, yield: 50.89%). Compound 94: ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.76 – 3.72 (m, 1H), 3.64 – 3.56 (m, 1H), 2.27 – 2.12 (m, 1H), 2.02 – 1.94 (m, 2H), 1.89 – 1.83 (m, 2H), 1.82 – 1.78 (m, 2H), 1.77 – 1.67 (m, 5H), 1.67 – 1.57 (m, 3H), 1.48 – 1.39 (m, 3H), 1.38 – 1.33 (m, 2H), 1.32 – 1.27 (m, 7H), 1.17 – 1.09 (m, 2H), 1.18 – 1.24 (m, 7H). (s, 3H), 1.02 – 0.97 (m, 1H), 0.94 (d, J = 6.5 Hz, 3H), 0.68 (s, 3H). ¹⁹ F NMR (377 MHz, CDCl ₃ ) δ -88.97 (d, J = 235.8 Hz, 1F), -110.95 (d, J = 235.7 Hz, 1F), -114.05 – -117.90 (m, 2F). Example 103 Preparation of Compound 103 3β,25-dihydroxy-5α-cholestane-7-carbonitrile

Step 1: Dissolve (1R,3aS,3bR,7S,9aS,9bS,11aR)-4-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate (200 mg, 0.432 mmol, 1 eq) in super dry pyridine (5 mL), then add 4-methylbenzenesulfonyl chloride (824 mg, 4.32 mmol, 10 eq) and stir at room temperature for 5 days. After the reaction is complete, add 30 ml 3M hydrochloric acid aqueous solution, extracted with ethyl acetate (30mL*3), and then the organic solvent was rotary dried to obtain a crude product. The crude product was purified by silica gel separation (petroleum ether: ethyl acetate = 10:1) to obtain the product 4-methylbenzenesulfonic acid-(1R,3aS,3bR,5aR,7S,9aS,9bS,11aR)-7-acetyloxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-4-yl ester (30 mg, 0.049 mmol, yield: 11%) as a white compound. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.77 (t, J = 7.9 Hz, 2H), 7.33 (dd, J = 17.9, 8.2 Hz, 2H), 4.76 – 4.44 (m, 2H), 2.44 (s, 3H), 2.00 (s, 3H), 1.77 (ddd, J =32.4, 24.9, 8.1 Hz, 8H), 1.52 – 1.32 (m, 13H), 1.29 – 1.24 (m, 4H), 1.22 (d, J = 4.4 Hz, 6H), 1.15 – 1.02 (m, 5H), 0.90 (d, J = 6.4 Hz, 3H), 0.79 (d, J =15.5 Hz, 3H), 0.62 (d, J = 7.6 Hz, 3H).

In the second step, compound 4-methylbenzenesulfonic acid-(1R,3aS,3bR, 5aR,7S,9aS,9bS,11aR)-7-acetyloxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-4-yl ester 103-1 (60 mg, 0.1 mmol, 1.0 eq) and sodium cyanide (20 mg, 0.4 mmol, 4 eq) were dissolved in DMF (2 mL), stirred at 65°C for 12 hours, and monitored by TLC (petroleum ether:ethyl acetate = 1:1). After the reaction was completed, water was added to quench, and then extracted with ethyl acetate (50 mL). The organic phase was washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and rotary dried to obtain a crude product, which was then purified by silica gel separation (petroleum ether: ethyl acetate = 1:1) to obtain acetic acid-(1R,3aS,3bR,7S,9aS,9bS,11aR)-4-cyano-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 103-2 (25 mg, 0.05 mmol, yield: 55%), and the crude product was directly used in the next step.

Step 3: Compound (1R, 3aS, 3bR, 7S, 9aS, 9bS, 11aR)-4-cyano-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate 103-2 (25 mg, 0.05 mmol, 1 eq) was dissolved in methanol (2 mL), potassium carbonate (29 mg, 0.212 mmol, 4 eq) was added, stirred at room temperature for 3 hours, monitored by TLC (petroleum ether: ethyl acetate = 4:1), after the reaction was completed, water was added to quench, and then extracted with ethyl acetate (50 mL), the organic phase was washed twice with saturated brine, the organic phase was dried over anhydrous sodium sulfate, filtered, The crude product was rotary dried and then purified by silica gel separation (petroleum ether: ethyl acetate = 4:1) to obtain 3β,25-dihydroxycholester-7-carbonitrile 103 (16 mg, 0.037 mmol, yield: 70%). Compound 103 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.67 (s, 1H), 2.84 (s, 1H), 2.00 – 1.95 (m, 1H), 1.92 – 1.81 (m, 2H), 1.75 – 1.67 (m, 2H), 1.59 (s, 2H), 1.54 (s,2H), 1.46 – 1.37 (m, 8H), 1.33 – 1.27 (m, 5H), 1.22 (s, 6H), 1.19 (s, 1H), 1.13 – 1.01 (m, 5H), 0.92 (d, J = 6.5 Hz, 3H), 0.81 (d, J = 4.2 Hz, 3H), 0.66 (s, 3H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 121.18, 71.10, 70.63, 55.76, 52.83, 49.11, 44.38, 42.74, 40.40, 39.01, 37.16, 36.36, 36.28, 35.61, 35.49, 32.36,31.14, 30.80, 29.29, 29.27, 28.04, 23.60, 20.89, 20.66, 18.57, 12.03, 11.92. Example 106 Compound 106 Preparation of 24-[ Hydroxy (2- methoxyphenyl ) methyl ]-7- methylidene -5α- cholane- 3β,4β- diol

Step 1: Dissolve the raw material 1-bromo-2-methoxybenzene (7.64 g, 40.82 mmol, 3.5 eq ) in anhydrous tetrahydrofuran (50 mL), cool the system to -78 ^o C, add n-butyl lithium (14.0 mL, 34.99 mmol, 3.0 eq ), and stir at the same temperature for 30 min. Compound (R)-5-(((3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12bR)-2,2,5a, 7a-tetramethyl-3a, 5,5a, 5b, 6,7,7a, 8,9,10,10a, 10b, 11,12b-tetrahydro-4H-cyclopentyl[7,8]phenanthrene[1,2-d][1,3]dioxy-8-yl)hexanal III (5 g, 11.66 mmol, 1.0 eq) was dissolved in tetrahydrofuran (5 mL) and added to the above reaction solution. The reaction system was stirred at -78 ^° C for 30 min. The reaction progress was monitored by TLC (petroleum ether: ethyl acetate = 5:1). The raw material was completely consumed. 10 mL Water was added to the reaction system, and ethyl acetate (100 mL × 3) was used for extraction. The combined organic phases were washed with saturated sodium chloride (100 mL), and the combined organic phases were dried and concentrated to obtain a crude product. The crude product was chromatographed on a silica gel column (petroleum ether: ethyl acetate = 90: 10) to obtain white solid (5R)-5-[(3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12b-tetrahydro-3aH-cyclopentadienyl[1',2':1,2]phenanthrene[7,8-d][1,3]dioxacyclo-8-yl]-1-(2-methoxyphenyl)hexan-1-ol 106-1 (4.9 g, purity 90%, yield 70.43%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.32 – 7.28 (m, 1H), 7.26 – 7.20 (m, 1H), 7.02 – 6.82 (m, 2H), 5.80 (d, J = 2.7 Hz, 1H), 4.85 (dt, J = 9.9, 5.8 Hz, 1H), 4.41 (d, J = 5.8 Hz, 1H), 4.10 (dd, J = 13.6, 6.4 Hz, 1H), 3.84 (d, J = 10.0 Hz, 3H), 2.19 – 1.98 (m, 3H), 1.82 – 1.72 (m, 3H), 1.63 (dd, J = 13.2, 8.6 Hz, 5H), 1.53 (s, 4H), 1.43 (s, 3H), 1.35 (s, 3H), 1.28 – 1.23 (m, 1H), 1.16 (s, 4H), 1.13 – 1.01 (m, 25H), 0.95 – 0.88 (m, 4H), 0.72 – 0.64 (m, 3H).

Step 2: In a 200 mL round-bottom flask at room temperature, (5R)-5-[(3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12b-tetrahydro-3aH-cyclopentadienyl[1',2':1,2]phenanthrene[7,8-d][1,3]dioxacyclo-8-yl]-1-(2-methoxyphenyl)hexan-1-ol 106-1 (4.9 g, 9.13 mmol) was dissolved in dichloromethane (70 mL). tert-Butyldimethylsilyl chloride (4.13 g, 27.39 mmol) was added at room temperature. mmol), 4-dimethylaminopyridine (450 mg, 3.65 mmol) and imidazole (2.49 g, 36.51 mmol), and then stirred at room temperature for 2 hours. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 5:1). After the reaction was completed, it was diluted with water (100 mL), extracted with ethyl acetate (100 mL×3), and the organic phase was saturated with brine (50 The mixture was washed with 1% 4-nitropropene (2-nitropropene) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 10:1) to obtain a white solid (9R)-9-[(3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12b-tetrahydro-3aH-cyclopentadienyl[1',2':1,2]phenanthrene[7,8-d][1,3]dioxadienyl]-5-(2-methoxyphenyl)-2,3,3-tetramethyl-4-oxo-3-siladecane 106-2 (4.9 g, purity: 90%, yield: 74%). ¹ H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.6 Hz, 1H), 7.36 – 7.27 (m, 1H), 7.11 – 7.01 (m, 1H), 6.95 (d, J = 8.1 Hz, 1H), 5.94 (d, J = 2.7 Hz, 1H), 5.21 (dt, J = 7.5, 3.9 Hz, 1H), 4.55 (d, J = 5.8 Hz, 1H), 4.25 (t, J = 5.8 Hz, 1H), 3.95 (s, 3H), 2.30 – 2.20 (m, 1H), 2.20 – 2.11 (m, 2H), 1.96 (ddd, J = 13.1, 7.8, 3.9 Hz, 1H), 1.91 – 1.60 (m, 13H), 1.58 – 1.45 (m, 7H), 1.41 (dd, J = 13.1, 6.0 Hz, 3H), 1.36 – 1.26 (m, 5H), 1.26 – 1.09 (m, 5H), 1.08 – 1.01 (m, 12H), 1.01 – 0.90 (m, 1H), 0.87 – 0.78 (m, 3H), 0.21 – 0.15 (m, 3H).

Step 3: In a 250 mL round-bottom flask at room temperature, (9R)-9-[(3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12b-tetrahydro-3aH-cyclopentadienyl[1',2':1,2]phenanthrene[7,8-d][1,3]dioxacyclo-8-yl]-5-(2-methoxyphenyl)-2,3,3-tetramethyl-4-oxo-3-siladecane 106-2 (4.9 g, 7.53 mmol) was dissolved in acetone (100 mL) and the mixture was stirred for 2 h. mL), N-hydroxyphthalide (370 mg, 2.26 mmol), cobalt acetate (200 mg, 1.13 mmol) and tert-butyl hydroperoxide (3.39 g, 37.63 mmol) were added at room temperature, and then stirred at room temperature for 36 hours. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 10:1). After the reaction was completed, it was quenched with water (50 mL), extracted with ethyl acetate (100 mL×3), and the organic phase was saturated with brine (60 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) to obtain a white solid (3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxo-3-silyl]-2,2,5a, 7a, 7a-tetramethyl-4,5,5a, 5b, 6,7,8,9,10,10a, 10b, 11,12b-tetrahydro-3aH-cyclopenta[1':1,2]phenanthro[7,8-d][1,3]dioxy-11,5-one 106-3 (2.6 g, purity: 90%, yield: 46.75%). ¹ H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 7.5 Hz, 1H), 7.37 – 7.27 (m, 1H), 7.08 (t, J = 7.4 Hz, 1H), 6.95 (d, J = 8.2 Hz, 1H), 6.06 (s, 1H), 5.22 (dd, J = 7.0, 3.3 Hz, 1H), 4.66 (d, J = 6.4 Hz, 1H), 4.47 (q, J = 5.5 Hz, 1H), 3.95 (s, 3H), 2.55 – 2.43 (m, 2H), 2.24 – 2.14 (m, 1H), 2.05 – 1.93 (m, 2H), 1.81 – 1.67 (m, 11H), 1.55 – 1.39 (m, 15H), 1.31 – 1.18 (m, 3H), 1.06 – 0.99 (m, 13H), 0.87 – 0.80 (m, 3H), 0.16 (q, J = 7.4 Hz, 3H).

Step 4: (3aS,5aR,5bS,7aR,8R,10aS, 10bS,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6, 7,7a,8,9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[11-one 106-3 (2.1 g, 3.158 mmol) was dissolved in methanol (30 mL). Pd/C (1.08 g, 5.052 mmol), the system was replaced with hydrogen, and the reaction solution was stirred at room temperature for 2 hours. The reaction solution was filtered through diatomaceous earth, the filtrate was rotary dried and purified by silica gel column chromatography to obtain (3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7, 7a,8,9,10,10a,10b,11, 12,12a,12b-Hexadecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[11-one 106-4 (1.1 g, 1.402 mmol, 44.39%) was obtained as a white solid. ¹ H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 7.6 Hz, 1H), 7.22 – 7.14 (m, 1H), 6.94 (t, J = 7.4 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 5.06 (s, 1H), 4.01 (s, 1H), 4.00 – 3.93 (m, 1H), 3.81 (s, 3H), 2.77 (s, 1H), 2.42 (s, 1H), 2.19 (dd, J = 12.7, 2.6 Hz, 2H), 1.98 (d, J = 12.9 Hz, 1H), 1.93 – 1.82 (m, 2H), 1.79 – 1.67 (m, 2H), 1.63 (dd, J = 14.5, 3.1 Hz, 2H), 1.55 (s, 4H), 1.48 (d, J = 3.6 Hz, 2H), 1.45 – 1.34 (m, 4H), 1.30 (s, 6H), 1.21 (s, 2H), 1.06 (dt, J = 11.1, 8.1 Hz, 4H), 0.99 (d, J = 5.6 Hz, 1H), 0.96 (d, J = 6.7 Hz, 1H), 0.88 (s, 9H), 0.64 (d, J = 5.5 Hz, 3H), 0.02 (d, J = 1.8 Hz, 3H), -0.00 (s, 3H), -0.14 (s, 3H).

Step 5: Place methyltriphenylphosphonium bromide (696.19 mg, 1.949 mmol) in a two-necked flask (50 mL), replace the atmosphere with nitrogen, add ultra-dry tetrahydrofuran (15 mL), stir at 0°C, and add potassium tert-butoxide (1.949 mL, 1.949 mmol) in tetrahydrofuran dropwise. Continue stirring at 0°C for 10 minutes. (3aS,5aR, 5bS,7aR,8R,10aS,10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[11-one] 106-4 (260 mg, 0.390 mmol) was dissolved in super dry tetrahydrofuran (5 mL) was added dropwise to the reaction bottle, and the reaction mixture was stirred at room temperature for 1 hour. The reaction was quenched with 5% sodium dihydrogen phosphate solution, extracted with ethyl acetate, and the organic phase was purified by silica gel column chromatography (petroleum ether/dichloromethane = 2/1) to obtain (9R)-9-[(3aS, 5aR, 5bS, 7aR, 8R,10aS,10bS,12aR,12bR)-2,2,5a,7a-tetramethyl-11-methylidene-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladecane 106-5 (210 mg, 0.253 mmol, 64.81%) was a colorless transparent oil. ¹ H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.6 Hz, 1H), 7.36 – 7.28 (m, 1H), 7.08 (t, J = 7.4 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 5.21 (dt, J = 7.8, 4.1 Hz, 1H), 4.85 (s, 1H), 4.73 (s, 1H), 4.21 – 4.16 (m, 1H), 4.16 – 4.07 (m, 1H), 3.95 (s, 3H), 2.53 (t, J = 12.8 Hz, 1H), 2.24 (d, J = 10.4 Hz, 2H), 2.12 (t, J = 14.2 Hz, 3H), 2.04 – 1.90 (m, 3H), 1.79 (ddd, J = 14.0, 11.9, 3.6 Hz, 3H), 1.72 (s, 2H), 1.66 (s, 4H), 1.58 – 1.49 (m, J = 9.1, 3.9 Hz, 6H), 1.45 (s, 3H), 1.41 – 1.37 (m, 2H), 1.31 (s, 3H), 1.24 (dd, J = 11.4, 7.0 Hz, 2H), 1.18 – 1.11 (m, 2H), 1.03 (s, 9H), 0.93 – 0.86 (m, 1H), 0.82 (s, 3H), 0.15 (dd, J = 7.9, 2.2 Hz, 4H), -0.00 (s, 3H).

Step 6: (9R)-9-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-2,2,5a,7a-tetramethyl-11-methylidene-4,5,5a,5b,6, 7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladecane 106-5 (18 mg, 0.027 mmol) was dissolved in tetrahydrofuran (1 mL), hydrochloric acid (2.520 mL, 7.560 mmol) was added, stirred at 40°C for 3 hours, and the reaction was monitored by TLC (petroleum ether: ethyl acetate = 1:1). The raw material was reacted. Water was added to the reaction solution, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and rotary dried. The crude product was purified by silica gel column chromatography (PE/EA = 1/1) to obtain 24-[hydroxy(2-methoxyphenyl)methyl]-7-methylidene-5α-cholane-3β,4β-diol 106 (6 mg, 0.011 mmol, 41.24%) as a white solid. Compound 106 : ¹ H NMR (400 MHz, CDCl3) δ 7.30 (d, J = 5.8 Hz, 1H), 7.24 (d, J = 7.8 Hz, 1H), 6.97 (dd, J = 15.5, 8.1 Hz, 1H), 6.88 (d, J = 8.3 Hz, 1H), 4.91 – 4.80 (m, 1H), 4.65 (d, J = 42.3 Hz, 2H), 3.86 (s, 3H), 3.79 (s, 1H), 3.61 – 3.49 (m, 1H), 2.49 (t, J = 12.8 Hz, 1H), 2.03 – 1.92 (m, 5H), 1.84 (dd, J = 13.7, 1H). = 23.5, 14.4 Hz, 2H), 1.78 – 1.66 (m, 5H), 1.40 (d, J = 2.7 Hz, 3H), 1.34 – 1.28 (m, 2H), 1.25 (s, 2H), 1.18 (s, 1H), 1.15 (s, 3H), 1.11 (d, J = 11.3 Hz, 3H), 1.01 – 0.96 (m, 1H), 0.92 (dd, J = 6.4, 3.9 Hz, 3H), 0.75 (t, J = 9.3 Hz, 1H), 0.67 (d, J = 2.5 Hz, 3H). LC-MS: [M+H-H2O] ⁺ = 493.45 Example 109 Preparation of Compound 109 3β,25-dihydroxy-5α-cholestane-4-carbonitrile

Step 1: In a 50 mL round-bottom flask at room temperature, 3β-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-25-hydroxycholest-6(5)-ene-4-carbaldehyde 23-3 (90 mg, 0.17 mmol) was dissolved in acetonitrile (6 mL), sodium acetate (230 mg, 2.8 mmol), hydroxylamine hydrochloride (115 mg, 1.7 mmol) and water (2 ml) were added at room temperature, and then stirred at room temperature for 30 hours. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 4:1). After the reaction was completed, it was quenched with water (20 mL), extracted with ethyl acetate (20 mL×3), and the organic phase was saturated with brine (30 The reaction mixture was washed with 4% paraformaldehyde (2-nitropropane) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1) to obtain a white solid [(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methanealdehyde oxime 109-1 (53 mg, purity: 90 %, yield: 51.58 %). ¹ H NMR (400 MHz, CDCl ₃ ) δ = 7.59 (d, J=9.2, 1H), 3.75 (dd, J=15.4, 5.9, 1H), 2.61 – 2.54 (m, 1H), 2.01 – 1.27 (m, 25H), 1.21 (s, 6H), 1.11 – 1.00(m, 5H), 0.91 (d, J=6.5, 3H), 0.85 (s, 9H), 0.79 (s, 3H), 0.62 (s, 3H), 0.03 (d, J=3.0, 6H).

Step 2: In a 50 mL round-bottom flask at room temperature, [(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methanealdehyde oxime 109-1 (43 mg, 0.077 mmol) was dissolved in tetrahydrofuran (2.5 mL). Diphenyl disulfide (67 mg, 0.31 mmol) and tributylphosphine (62 mg, 0.31 mmol), then stirred at room temperature for 6 hours, the reaction was monitored by TLC (petroleum ether: ethyl acetate = 8:1), after the reaction was completed, quenched with water (10 mL), extracted with ethyl acetate (10 mL×3), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 8:1) to obtain white solid 3β-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-25-hydroxycholester-4-carbonitrile 109-2 (31 mg, purity: 90 %, yield: 67.04 %). ¹ H NMR (400 MHz, CDCl ₃ ) δ = 3.61 – 3.50 (m, 1H), 2.69 (t, J=4.7, 1H), 1.95 – 1.21 (m, 26H), 1.14 (s, 6H), 1.01 (s, 3H), 0.98 – 0.88 (m, 3H), 0.84(d, J=5.0, 12H), 0.58 (s, 3H), -0.00 (s, 6H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 142.57, 119.68, 71.12, 70.74, 56.45, 56.12, 55.12, 45.76, 44.41, 42.55, 40.84, 39.80, 36.60, 36.41, 36.14, 35.71, 35.19, 31.90, 31.52, 29.71, 29.40, 29.20, 29.07, 28.22, 27.08, 25.71, 24.17, 20.72, 18.64, 18.02, 13.09, 12.05.

Step 3: In a 50 mL round-bottom flask at room temperature, 3β-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-25-hydroxycholest-4-carbonitrile 109-2 (31 mg, 0.057 mmol) was dissolved in 1 mol tetrabutylammonium fluoride tetrahydrofuran solution (2 mL), stirred at room temperature for 2 hours, and the reaction was monitored by TLC (petroleum ether:ethyl acetate = 4:1). After the reaction was completed, the mixture was quenched with water (10 mL), extracted with ethyl acetate (10 mL×3), and the organic phase was saturated with brine (20 mL) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain white solid 3β,25-dihydroxy-5α-cholestane-4-carbonitrile 109 (18.02 mg, purity: 100 %, yield: 73.59 %). Compound 109 : ¹ H NMR (400 MHz, CDCl ₃ ) δ = 3.73 – 3.63 (m, 1H), 2.95 (t, J=4.3, 1H), 2.03 – 1.25 (m, 26H), 1.21 (s, 6H), 1.09 (s, 3H), 1.07 – 0.95 (m, 4H), 0.91(d, J=6.5, 3H), 0.65 (s, 3H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 119.61, 71.13, 70.24, 56.38, 56.12, 54.98, 45.71, 44.40, 42.54, 40.17, 39.73, 36.66, 36.40, 36.13, 35.71, 35.17, 31.83, 29.71, 29.39, 29.20, 28.71, 28.21, 27.11, 24.16, 20.74, 18.64, 13.06, 12.05. LC-MS: [M+HH ₂ O] ⁺ = 412.5. Example 114 Preparation of Compound 114 24-[ Hydroxy (2- methoxyphenyl ) methyl ]-7-( hydroxymethyl )-5α- cholane- 3β,4β- diol

Step 1: Dissolve (9R)-9-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-2,2,5a,7a-tetramethyl-11-methylidene-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladecane 106-5 (180 mg, 0.271 mmol) in ultra-dry tetrahydrofuran (5 mL), replaced with nitrogen, and borane dimethyl sulfide (0.406 mL, 0.812 mmol) was added under an ice-water bath. The mixed solution was stirred at room temperature for 2 hours. Then, sodium hydroxide aqueous solution (0.162 mL, 1.624 mmol) and hydrogen peroxide (184.09 mg, 1.624 mmol) were added dropwise to the reaction solution. The mixed solution was stirred at room temperature overnight. The reaction solution was quenched with sodium bisulfite aqueous solution, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and rotary dried. The crude product was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 3/1) to obtain [(3aS, 5aR, 5bS, 7aR, 8R, 10aS,10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[11-yl]methanol 114-1 (90 mg, 0.112 mmol, 41.38%) was obtained as a white solid. ¹ H NMR (400 MHz, cdcl3) δ 7.60 (d, J = 7.6 Hz, 1H), 7.36 – 7.29 (m, 1H), 7.09 (d, J = 6.9 Hz, 1H), 6.95 (d, J = 8.2 Hz, 1H), 5.21 (dt, J = 7.6, 3.9 Hz, 1H), 4.14 (s, 2H), 3.96 (d, J = 3.3 Hz, 3H), 3.90 (s, 1H), 3.83 (s, 1H), 2.05 (s, 2H), 1.93 (dt, J = 8.5, 4.3 Hz, 5H), 1.87 – 1.83 (m, 1H), 1.81 (d, J = 2.3 Hz, 1H), 1.75 (dd, J = 13.1, 3.3 Hz, 3H), 1.71 – 1.67 (m, 2H), 1.66 (s, 4H), 1.53 (ddd, J = 15.3, 9.1, 3.3 Hz, 5H), 1.44 (s, 3H), 1.42 (d, J = 2.8 Hz, 1H), 1.41 – 1.38 (m, 3H), 1.23 (s, 3H), 1.18 (d, J = 9.5 Hz, 2H), 1.03 (d, J = 2.9 Hz, 9H), 1.01 (d, J = 2.2 Hz, 2H), 0.98 – 0.91 (m, 1H), 0.78 (s, 3H), 0.19 – 0.11 (m, 4H), 0.00 (d, J = 0.9 Hz, 3H).

Step 2: Dissolve [(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7, 7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[11-yl]methanol 114-1 (20 mg, 0.029 mmol) in tetrahydrofuran (1 mL) Hydrochloric acid (2 mL, 6.000 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and rotary dried. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:4) to give 24-[hydroxy(2-methoxyphenyl)methyl]-7-(hydroxymethyl)-5α-cholane-3β,4β-diol as a white solid 114 (4 mg, 0.007 mmol, 23.26%). Compound 114 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.27 (s, 1H), 7.25 (s, 1H), 6.96 (s, 1H), 6.89 (d, J = 8.2 Hz, 1H), 4.83 (d, J = 7.0 Hz, 1H), 3.86 (s, 3H), 3.77 (d, J = 6.9 Hz, 1H), 3.73 (s, 1H), 3.67 (t, J = 10.6 Hz, 1H), 3.58 (d, J = 10.9 Hz, 1H), 1.88 (d, J = 12.5 Hz, 5H), 1.76 – 1.63 (m, 7H), 1.39 (dd, J = 13.8, 7.3 Hz, 3H), 1.34 – 1.24 (m, 5H), 1.07 (s, 3H), 1.00 (d, J = 13.9 Hz, 3H), 0.93 – 0.87 (m, 3H), 0.81 (dd, J = 13.8, 9.3 Hz, 2H), 0.63 (d, J = 2.3 Hz, 3H), 0.07 (s, 2H). LC-MS: [M+H-2H ₂ O] ⁺ = 493.45. Example 118 Preparation of Compound 118 4-( Hydroxymethyl )-5α- cholestane -3β,25- diol

Step 1: Dissolve compound (5R)-5-[(1R,3aS,3bS,6R,7S, 9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-8 (150 mg, 0.326 mmol, 1.0 eq) in ethyl acetate (5 mL), add platinum dioxide (36.97 mg, 0.163 mmol, 0.5 eq), and stir the resulting mixture in the reaction solution in H ₂ at 25°C for 3 h. The reaction progress was monitored by TLC (petroleum ether: ethyl acetate = 3:1), and the starting material was completely consumed. The filtrate was filtered and concentrated to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether: ethyl acetate: 80:20) to obtain white solid (5R)-5-[(1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-7-acetyloxy-6-hydroxy-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester IV-1 (100 mg, 59.74%). ¹ H NMR (400 MHz, CDCl3) δ 4.72 (m, 1H), 3.83 (s, 1H), 3.66 (s, 3H), 2.27 (dd, J = 16.4, 8.7 Hz, 2H), 2.10 (d, J = 8.1 Hz, 3H), 1.79 (dddd, J = 37.0, 16.1,10.1, 3.7 Hz, 8H), 1.29 (m, 8H), 0.99 (m, 14H), 0.62 (d, J = 14.3 Hz, 4H).

Step 2: In a 50 mL round-bottom flask, (5R)-5-[(1R,3aS, 3bS,7S,9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester IV-1 (200 mg, 0.43 mmol) was dissolved in dichloromethane (10 mL), N-methyl porphyrin oxide (76 mg, 0.65 mmol), tetrapropylammonium perruthenate (30 mg, 0.086 mmol) and tetraA molecular sieve (190 mg, 0.43 mmol) were added at room temperature, and the mixture was stirred at room temperature for 24 hours. The reaction was monitored by TLC (petroleum ether/ethyl acetate = 10/1). After the reaction was completed, water (50 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (30 mL×3). The extracted organic solution was washed with saturated brine (50 mL), dried with anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified and separated by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 10/1) to obtain white solid (5R)-5-[(1R,3aS,3bS,7S,9aR, 9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-6-oxoylidenehexahydro-1H-cyclopenta[1,2-a]phenanthren-1-yl]hexanoic acid methyl ester 118-1 (170 mg, purity: 90%, yield: 76.83%). ¹ H NMR (400 MHz, CDCl3) δ 5.16 (dd, J = 12.0, 7.5 Hz, 1H), 3.67 (s, 3H), 2.31 – 2.18 (m, 4H), 2.15 (d, J = 3.2 Hz, 3H), 2.01 – 1.00 (m, 25H), 0.92(d, J = 6.6 Hz, 3H), 0.75 (s, 3H), 0.65 (s, 3H). ¹³ C NMR (101 MHz, CDCl3) δ = 205.71, 174.32, 170.18, 76.20, 57.39, 56.06, 55.90, 54.24, 51.44, 42.67, 42.55, 39.80, 35.93, 35.48, 35.36, 34.91, 34.50, 30.23, 28.50, 28.12, 24.10, 21.70, 21.52, 20.75, 20.17, 18.54, 13.69, 12.03.

Step 3: In a 50 mL round-bottom flask, methyltriphenylphosphonium bromide (388 mg, 1.09 mmol) was suspended in tetrahydrofuran (4 mL) at room temperature, and 1M/L potassium tert-butoxide tetrahydrofuran solution (1.09 mL, 1.09 mmol) was added dropwise at 0°C. After the mixture was stirred at room temperature for 2 hours, (5R)-5-[(1R,3aS,3bS,7S,9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-6-oxyylidene hexahydro-1H-cyclopenta[1,2-a]phenanthren-1-yl]hexanoic acid methyl ester 118-1 (100 mg, 0.22 mmol) in tetrahydrofuran (1 mL) solution, and the mixture was stirred at room temperature for 5 hours. The reaction was monitored by TLC (petroleum ether/ethyl acetate = 10/1). After the reaction was completed, water (30 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL×3). The extracted organic solution was washed with saturated brine (40 mL), dried with anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified and separated by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 10/1) to obtain white solid (5R)-5-[(1R,3aS,3bS, 5aR,7S,9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthren-1-yl]hexanoic acid methyl ester 118-2 (64 mg, purity: 90%, yield: 57.85%). ¹ H NMR (400 MHz, CDCl3) δ 5.20 (d, J = 11.1 Hz, 1H), 4.69 (s, 1H), 4.59 (s, 1H), 3.66 (s, 3H), 2.31 – 2.25 (m, 3H), 2.13 (s, 3H), 2.06 – 1.64 (m,9H), 1.60 – 1.29 (m, 13H), 1.12 – 1.02 (m, 5H), 0.96 (s, 3H), 0.91 (d, J = 6.5 Hz, 3H), 0.65 (s, 3H). ¹³ C NMR (101 MHz, CDCl3) δ = 174.35, 170.56, 147.24, 129.65, 115.27, 103.83, 74.35, 56.35, 55.90, 54.43, 52.43, 51.44, 42.52, 39.90, 39.43, 37.97,35.49, 35.39, 34.99, 34.53, 31.34, 30.49, 28.16, 24.12, 23.47, 21.53, 21.00, 20.90, 18.55, 13.22, 12.05.

Step 4: In a 50 mL round-bottom flask at room temperature, dissolve (5R)-5-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 118-2 (68 mg, 0.15 mmol) in anhydrous tetrahydrofuran (4 mL). Under nitrogen protection, cool to 0 ^° C, and add 3 mol/L methyl magnesium bromide tetrahydrofuran solution (0.50 mL, 1.50 mmol). mmol), then stirred at room temperature for 2 hours, and the reaction was monitored by TLC (petroleum ether: ethyl acetate = 4:1). After the reaction was completed, the system was cooled to 0 ^o C and quenched with saturated aqueous ammonium chloride solution (15 mL), extracted with ethyl acetate (10 mL×3), and the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain white solid 4-methylidenecholestane-3β,25-diol 118-3 (34 mg, purity: 90%, yield: 46.46%). ¹ H NMR (400 MHz, CDCl3) δ = 4.83 (dd, J=115.4, 50.6, 2H), 4.07 – 3.81 (m, 1H), 2.27 (dt, J=16.4, 8.4, 1H), 1.97 (dd, J=10.2, 3.8, 2H), 1.85 – 1.72 (m, 4H), 1.63 – 1.32 (m, 20H), 1.26 (s, 3H), 1.21 (s, 6H), 1.12 – 1.00 (m, 6H), 0.91 (s, 3H), 0.66 (s, 3H). ¹³ C NMR (101 MHz, CDCl3) δ 152.30, 151.31, 102.19, 101.34, 72.35, 71.24, 70.11, 55.38, 55.24, 55.20, 55.13, 54.36, 53.48, 53.45, 48.86, 43.40, 41.58, 41.50, 39.04, 38.94, 38.63, 37.58, 36.75, 36.23, 35.39, 34.72, 34.22, 33.99, 32.02, 30.56, 29.46, 28.68, 28.34, 28.32, 28.19, 27.25, 23.23, 23.18, 23.13, 22.44, 21.67, 20.69, 19.98, 19.75, 17.61, 13.11, 12.30, 11.91, 11.05, 11.04.

Step 5: In a 50 mL round-bottom flask, 4-methylidenecholestane-3β,25-diol 118-3 (34 mg, 0.082 mmol) was dissolved in tetrahydrofuran (4 mL) at room temperature, and a 2-mole per liter solution of borane dimethyl sulfide complex in tetrahydrofuran (0.12 mL, 0.24 mmol) was added dropwise at 0°C. After the mixture was stirred at room temperature for 3 hours, a 10-mole per liter aqueous sodium hydroxide solution (0.049 mL, 0.49 mmol) and a 30% aqueous hydrogen peroxide solution (56 mg, 0.49 mmol) were added dropwise to the reaction solution at 0°C, and the mixture was stirred at room temperature for 16 hours. The reaction was monitored by TLC (petroleum ether/ethyl acetate = 2/1). After the reaction was completed, water (10 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (10 mL×3). The extracted organic solution was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified and separated by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 2/1) to obtain white solid 4-(hydroxymethyl)-5α-cholestane-3β,25-diol 118 (22.27 mg, purity: 73.65%, yield: 46.05%). ¹ H NMR (400 MHz, CDCl3) δ = 4.26 (t, J=10.3, 1H), 3.84 (dd, J=11.2, 5.1, 1H), 3.60 – 3.53 (m, 1H), 2.35 – 2.27 (m, 1H), 2.05 – 1.66 (m, 15H), 1.59 – 1.33 (m, 16H), 1.21 (s, 6H), 0.91 (d, J=6.5, 3H), 0.81 (s, 3H), 0.65 (s, 3H). ¹³ C NMR (101 MHz, DMSO) δ = 99.99, 68.64, 66.35, 59.50, 51.76, 51.45, 49.90, 42.50, 39.68, 37.77, 36.43, 35.21, 33.06, 31.69, 31.01, 30.32,28.83, 26.77, 24.96, 24.60, 24.47, 23.51, 19.38, 18.86, 17.78, 16.05, 13.89, 8.16, 7.33. LC-MS: [M+H-2H ₂ O] ⁺ =399 Example 13 Preparation of Compound 13 Acetate -[(1R,3aS,3bS,5aS,7S,9aR,9bS,11aR)-7- Hydroxy -1-[(2R)-6- Hydroxy - 6- methylhept -2- yl ]-9a,11a -dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -6- yl ] methyl ester and Acetate -[(1R,3aS,3bS,5aS,7S,9aR,9bS,11aR)-7- acetoxy -1-[(2R)-6- Hydroxy -6- methylhept -2- yl ]-9a,11a -dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -6- yl ] methyl ester

Step 1: In a 50 mL round-bottom flask at room temperature, 4-(hydroxymethyl)-5α-cholestane-3β,25-diol 118 (180 mg, 0.41 mmol) was dissolved in dichloromethane (2 mL) and tetrahydrofuran (2 mL). Triethylamine (126 mg, 1.24 mmol), 4-dimethylaminopyridine (5 mg, 0.041 mmol) and acetic anhydride (42 mg, 0.41 mmol) were added at room temperature. The mixture was stirred at room temperature for 1 hour and the reaction was monitored by TLC (petroleum ether: ethyl acetate = 3:1). After the reaction was completed, the reaction mixture was quenched with water (30 mL), extracted with ethyl acetate (20 mL×3), the organic phase was washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain white solid acetic acid-[(1R,3aS,3bS,5aS,7S,9aR,9bS,11aR)-7-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methyl ester 13 (180 mg, purity: 90%, yield: 82.06%). Compound 13 : ¹ H NMR (400 MHz, CDCl3) δ = 4.34 – 4.18 (m, 2H), 3.81 – 3.72 (m, 1H), 2.04 (s, 3H), 1.99 – 1.93 (m, 1H), 1.82 – 1.69 (m, 4H), 1.68 – 1.51 (m, 9H), 1.44 – 1.33 (m, 8H), 1.29 – 1.24 (m, 4H), 1.21 (s, 6H), 1.09 – 0.95 (m, 5H), 0.91 (d, J=6.5, 3H), 0.73 (s, 3H), 0.63 (s, 3H). ¹³ C NMR (101 MHz, CDCl3) δ = 171.05, 73.11, 71.12, 61.73, 56.46, 56.14, 55.32, 47.67, 46.37, 44.42, 42.51, 39.84, 37.20, 36.42, 35.73, 35.55, 32.54, 29.37, 29.20, 28.23, 26.91, 26.76, 24.23, 21.25, 20.89, 20.77, 18.63, 14.03, 12.01. Example 119 Compound 119 Preparation of 4β- hydroxy -3β- hydroxy -24-[ hydroxy (2- methoxyphenyl ) methyl ]-5α- cholane -7-carboxylic acid

Step 1: Dissolve [(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9, 10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[11-yl]methanol 114-1 (70 mg, 0.102 mmol) in dichloromethane 99.9% (3 mL), add N-methyl morpholine oxide (21 mg, 0.179 mmol), tetrapropylammonium perruthenate (14 mg, 0.040 mmol) and molecular sieves. The mixture is stirred at room temperature for 30 minutes. Add water, extract with ethyl acetate, wash the organic phase with saturated brine and dry with anhydrous sodium sulfate, and spin dry. The crude product was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 4/1) to obtain (3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a, 10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopentane-11-carbaldehyde 119-1 (60 mg, 73.08%) as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.95 (s, 1H), 7.45 (d, J = 7.7 Hz, 1H), 7.18 (s, 1H), 6.94 (s, 1H), 6.81 (d, J = 8.2 Hz, 1H), 5.07 (d, J = 3.6 Hz, 1H), 4.00 (s, 2H), 3.81 (d, J = 3.4 Hz, 3H), 2.59 (s, 1H), 1.97 (d, J = 12.8 Hz, 1H), 1.85 (d, J = 5.4 Hz, 6H), 1.63 (d, J = 18.7 Hz, 5H), 1.50 (s, 3H), 1.43 (s, 3H), 1.35 (d, J = 15.3 Hz, 3H), 1.30 (s, 3H), 1.27 – 1.19 (m, 3H), 1.18 – 1.10 (m, 3H), 1.07 (s, 3H), 1.04 (s, 2H), 0.97 (d, J = 6.6 Hz, 1H), 0.89 (s, 9H), 0.67 (s, 2H), 0.02 (t, J = 2.7 Hz, 3H), 0.00 (d, J = 3.3 Hz, 6H).

Step 2: Dissolve (3aS,5aR,5bS,7aR,8R,10aS,10bS, 12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a, 8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopentane-11-carbaldehyde 119-1 (55 mg, 0.081 mmol) in tert-butyl alcohol (1 mL), add 2-methyl-2-butene (33.98 mg, 0.485 mmol) in an ice-water bath and stir for 1 minute. Then add sodium chlorite (25.56 mg, 0.283 mmol) aqueous solution and sodium dihydrogen phosphate (2.62 mg, 0.022 mmol) aqueous solution. Move the mixture to room temperature and stir for 1 hour. Add water to the reaction solution, extract with ethyl acetate, wash the organic phase with saturated sodium chloride solution and dry with anhydrous sodium sulfate, and spin dry. The crude product was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 3/1) to obtain (3aS,5aR,5bS,7aR,8R,10aS,10bS, 12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11, 12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopentane-11-carboxylic acid 119-2 (50 mg, 76.39%) as white solid. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.45 (d, J = 7.6 Hz, 1H), 7.17 (t, J = 7.7 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.80 (d, J = 8.2 Hz, 1H), 5.06 (dd, J = 7.1, 3.0 Hz, 1H), 3.99 (ddd, J = 14.2, 10.0, 5.0 Hz, 2H), 3.80 (s, 3H), 2.79 (s, 1H), 2.09 (dd, J = 13.4, 5.7 Hz, 1H), 1.93 (d, J = 11.3 Hz, 1H), 1.83 (dd, J = 13.9, 11.3 Hz, 4H), 1.69 (dd, J = 28.9, 9.6 Hz, 4H), 1.63 – 1.53 (m, 8H), 1.47 (s, 2H), 1.37 (dd, J = 21.0, 11.0 Hz, 4H), 1.29 (s, 3H), 1.19 (d, J = 15.1 Hz, 2H), 1.16 – 1.08 (m, 3H), 1.06 (s, 3H), 1.03 – 0.92 (m, 3H), 0.88 (s, 9H), 0.64 (s, 3H), 0.01 (s, 3H), -0.15 (s, 3H).

Step 3: Dissolve (3aS,5aR,5bS,7aR,8R,10aS,10bS, 12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9, 10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopentane-11-carboxylic acid 119-2 (50 mg, 0.072 mmol) in tetrahydrofuran (2 mL) , hydrochloric acid (1 mL, 3.000 mmol) was added. The mixture was stirred at 40°C for 2.5 hours. Water was added to the reaction solution, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and rotary dried. The crude product was purified by flash chromatography (petroleum ether/ethyl acetate = 90%-100%) to obtain 4β-hydroxy-3β-hydroxy-24-[hydroxy(2-methoxyphenyl)methyl]-5α-cholane-7-carboxylic acid 119 (11.5 mg, 0.015 mmol, 20.68%) as a white solid. Compound 119 : ¹ H NMR (400 MHz, DMSO) δ 11.71 (s, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.17 (t, J = 7.2 Hz, 1H), 6.92 (dd, J = 7.5, 3.9 Hz, 2H), 4.85 (s, 2H), 4.33 (d, J = 5.8 Hz, 1H), 3.98 (d, J = 2.7 Hz, 1H), 3.75 (s, 3H), 3.40 (s,1H), 3.28 (s, 1H), 2.54 (s, 1H), 2.02 (td, J = 13.3, 5.9 Hz, 1H), 1.87 (d, J = 11.1 Hz, 1H), 1.78 – 1.68 (m, 1H), 1.58 (dd, J = 11.4, 5.7 Hz, 2H), 1.48 (s, 3H), 1.40 (dd, J = 22.5, 13.8 Hz, 8H), 1.32 – 1.25 (m, 2H), 1.23(s, 1H), 1.21 – 1.11 (m, 2H), 1.09 – 0.97 (m, 4H), 0.96 (s, 3H), 0.90 (d, J = 13.1 Hz, 1H), 0.84 (d, J = 6.2 Hz, 3H), 0.59 (d, J = 2.3 Hz, 3H). LC-MS ：[M+HH ₂ O] ⁺ = 525.40. Examples 121 & 122 & 125 Compound 121 : [(1R, 3aS, 3bS, 5aS, 7S, 9aS, 9bS, 11aR)-4,4 -difluoro -7- hydroxy -1-[(2R)-6- hydroxy -6- methylhept -2- yl ]-9a, 11a -dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -6- yl ] acetonitrile, Compound 122 : (1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-4,4 -difluoro -1-[(2R)-6- hydroxy -6- methylhept -2- yl ]-9a,11a -dimethyl - 6-methylidene hexahydro -1H- cyclopenta [1,2-a] phenanthrene -7- ol and Compound 125 : Preparation of (1R,3aS,3bS,5aS,7S,9aS,9bS,11aR)-4,4 -difluoro -6-( hydroxymethyl )-1-[(2R)-6- hydroxy -6- methylhept -2- yl ]-9a,11a -dimethylhexahydro -1H- cyclopenta [1,2-a] phenanthrene -7- ol

Step 1: In a 50 mL round-bottom flask at room temperature, (1R,3aS,3bS, 5aR,6R,7S,9aR,9bS,11aR)-7-(benzyloxy)-4,4-difluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-ol 79-7A (790 mg, 1.445 mmol) was dissolved in 1,2-dichloroethane (60 mL). Dess-Martin periodinane (1838.04 mg, 4.335 mmol) was added at room temperature and stirred at room temperature for 2 hours. The reaction was monitored by TLC (ethyl acetate/petroleum ether = 4:1). After the reaction was completed, saturated aqueous sodium sulfite solution (30 mL) and saturated aqueous sodium bicarbonate solution (30 mL) were added to quench the reaction, and the mixture was extracted with dichloromethane (50 mL×3). The organic phase was washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, and the organic phase was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain a white solid (1R, 3aS, 3bS, 5aR, 7S, 9aR, 9bS, 11aR)-7-(benzyloxy)-4,4-difluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-one 121-1 (750 mg, purity: 90 %, yield: 85.76 %). ¹ H NMR (400 MHz, CDCl3) δ = 8.09 (d, J=7.5, 2H), 7.58 (t, J=7.4, 1H), 7.45 (t, J=7.7, 2H), 5.44 (dd, J=12.0, 7.4, 1H), 2.63 (d, J=12.3, 1H), 2.47 –2.37 (m, 1H), 2.23 – 1.23 (m, 25H), 1.22 (s, 6H), 0.94 (d, J=6.5, 3H), 0.85 (s, 3H), 0.68 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ = -90.57 (d, J = 240.1, 1F), -111.72 (d, J = 240.0, 1F).

Step 2: In a 50 mL round-bottom flask, methyltriphenylphosphonium bromide (1.3 g, 3.67 mmol) was dissolved in tetrahydrofuran (20 mL) at room temperature. 1 M/L potassium tert-butylate tetrahydrofuran solution (3.67 mL, 3.67 mmol) was added dropwise at 0°C, and the mixture was stirred at room temperature for 2 hours. A solution of (1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-(benzyloxy)-4,4-difluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-one 121-1 (400 mg, 0.73 mmol) in tetrahydrofuran (5 mL) was added dropwise to the reaction solution at room temperature, and the mixture was stirred at room temperature for 3 hours. The reaction was monitored by TLC (petroleum ether/ethyl acetate = 8/1). After the reaction was completed, water (30 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL×3). The extracted organic solution was washed with saturated brine (40 mL), dried with anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified and separated by silica gel column chromatography (petroleum ether/ethyl acetate = 8/1) to give white solid (6R)-6-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-(benzyloxy)-4,4-difluoro-9a,11a-dimethyl-6-methylidenehexahydro-1H-cyclopenta[1,2-a]phenanthren-1-yl]-2-methylheptan-2-ol 121-2 (158 mg, purity: 90 %, yield: 35.68 %). ¹ H NMR (400 MHz, CDCl3) δ = 8.18 – 8.06 (m, 2H), 7.59 (q, J=7.4, 1H), 7.48 (t, J=7.7, 2H), 5.47 (d, J=11.3, 1H), 4.77 (s, 1H), 4.73 (s, 1H), 2.45 – 2.34 (m, 2H), 2.18 – 1.34 (m, 25H), 1.21 (s, 6H), 1.06 (s, 3H), 0.93 (d, J=6.5, 3H), 0.68 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -89.23 (d, J=238.5, 1F), -110.87 (d, J=238.4, 1F).

Step 3: In a 50 mL round-bottom flask at room temperature, (6R)-6-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-(benzyloxy)-4,4-difluoro-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylheptan-2-ol 121-2 (158 mg, 0.29 mmol) was dissolved in tetrahydrofuran (2 mL) and methanol (2 mL). Lithium hydroxide, monohydrate (73 mg, 1.74 mmol) and water (1 mL) were added at room temperature. The mixture was stirred at room temperature for 2 hours. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 5:1). After the reaction was completed, water (10 mL), extracted with ethyl acetate (10 mL×3), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain a white solid (1R, 3aS, 3bS, 5aR, 7S, 9aR, 9bS, 11aR)-4,4-difluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethyl-6-methylidene hexahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 122 (120 mg, purity: 95%, yield: 86.52%). Compound 122 : ¹ H NMR (400 MHz, CDCl3) δ = 4.93 (d, J=1.2, 1H), 4.79 (d, J=1.4, 1H), 3.91 (d, J=11.0, 1H), 2.54 – 2.44 (m, 1H), 2.38 – 2.20 (m, 2H), 2.08 – 1.24 (m, 25H), 1.21 (s, 6H), 0.95 (s, 3H), 0.93 (d, J=6.5, 3H), 0.68 (s, 3H). ¹³ C NMR (101 MHz, CDCl3) δ = 151.10, 104.32, 71.25, 71.13, 55.20, 50.57, 50.22, 48.51, 44.39, 43.05, 41.65, 39.31, 38.82, 37.29, 36.40, 35.70,30.17, 29.31, 29.24, 28.49, 25.37, 20.95, 20.75, 18.73, 12.37, 11.87. ¹⁹ F NMR (376 MHz, CDCl3) δ = -89.00 (d, J=237.7, 1F), -110.95 (d, J=237.6, 1F). LC-MS: [M+H-2H ₂ O] ⁺ = 417.35.

Step 4: In a 50 mL round-bottom flask, (1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-4,4-difluoro-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 122 (213 mg, 0.47 mmol) was dissolved in tetrahydrofuran (12 mL) at room temperature, and a 2 mol/L tetrahydrofuran solution of borane dimethyl sulfide complex (0.71 mL, 1.41 mmol) was added dropwise at 0°C. After the mixture was stirred at room temperature for 3 hours, a 10 mol/L aqueous sodium hydroxide solution (0.28 mL, 4% sodium hydroxide) was added dropwise at 0°C. mL, 2.82 mmol) and 30% aqueous hydrogen peroxide solution (320 mg, 2.82 mmol), the mixture was stirred at room temperature for 16 hours. TLC (petroleum ether/ethyl acetate = 2/1) monitored the reaction. After the reaction was completed, water (20 mL) was added to the reaction solution, extracted with ethyl acetate (20 mL×3), the extracted organic solution was washed with saturated brine (30 mL), dried with anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified and separated by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 2/1) to give white solid (1R,3aS,3bS,5aS,7S,9aS,9bS,11aR)-4,4-difluoro-6-(hydroxymethyl)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 125 (184 mg, purity: 95%, yield: 78.92%). Compound 125 : ¹ H NMR (400 MHz, CDCl3) δ = 4.25 (t, J=10.6, 1H), 3.82 (dd, J=11.1, 5.3, 1H), 3.63 (dd, J=10.9, 4.2, 1H), 2.47 – 2.33 (m, 2H), 2.06 – 1.93 (m, 2H), 1.88 – 1.39 (m, 21H), 1.21 (s, 6H), 1.16 – 1.01 (m, 5H), 0.93 (d, J=6.5, 3H), 0.85 (s, 3H), 0.67 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -88.57 (d, J=237.7, 1F), -110.59 (d, J=237.6, 1F). ¹³ C NMR (101 MHz, CDCl3) δ 72.09, 71.11, 69.65, 66.63, 65.39, 64.38, 64.05, 63.39, 56.85, 55.25, 53.89, 50.87, 48.88, 46.80, 44.39, 43.03, 40.85, 39.27, 35.71, 30.18, 29.73, 29.34, 29.25, 28.50, 23.39, 20.76, 18.73, 11.86. LC-MS: [M+Na] ⁺ = 493.3,

Step 5: In a 50 mL round-bottom flask at room temperature, (1R,3aS,3bS, 5aS,7S,9aS,9bS,11aR)-4,4-difluoro-6-(hydroxymethyl)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 125 (159 mg, 0.34 mmol) was dissolved in 1,2-dichloroethane (8 mL). Triethylamine (205 mg, 2.04 mmol), 4-dimethylaminopyridine (41 mg, 0.34 mmol) and p-toluenesulfonyl chloride (129 mg, 0.68 mmol), followed by stirring at 50°C for 16 hours, and the reaction was monitored by TLC (petroleum ether:ethyl acetate=3:1). After the reaction was completed, the reaction mixture was quenched with water (20 mL), extracted with ethyl acetate (20 mL×3), the organic phase was washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain white solid 4-methylbenzenesulfonic acid-[(1R,3aS,3bS,5aS,7S,9aS,9bS,11aR)-4,4-difluoro-7-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methyl ester 121-3 (155 mg, purity: 90 %, yield: 66.09 %). ¹ H NMR (400 MHz, CDCl3) δ = 7.80 (d, J=8.3, 2H), 7.36 (d, J=8.1, 2H), 4.29 (dd, J=9.8, 4.2, 1H), 4.16 (t, J=9.8, 1H), 3.72 (dd, J=11.8, 5.1, 1H), 2.45 (s, 3H), 2.37 – 2.19 (m, 2H), 2.02 – 1.33 (m, 22H), 1.22 (s, 6H), 1.16 – 0.99 (m, 5H), 0.93 (d, J=6.5, 3H), 0.83 (s, 3H), 0.65 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -88.75 (d, J=238.4, 1F), -110.46 (d, J=238.3, 1F).

Step 6: In a 50 mL round-bottom flask at room temperature, 4-methylbenzenesulfonic acid [(1R,3aS,7S,9aS,11aR)-4,4-difluoro-7-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methyl ester 121-3 (45 mg, 0.072 mmol) was dissolved in N,N-dimethylformamide (2 mL), sodium cyanide (18 mg, 0.36 mmol) was added at room temperature, and then stirred at 100 ^° C for 16 hours. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 4:1). After the reaction was completed, the reaction mixture was quenched with water (10 mL), extracted with ethyl acetate (10 mL×3), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain white solid [(1R, 3aS, 3bS, 5aS, 7S, 9aS, 9bS, 11aR)-4,4-difluoro-7-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]acetonitrile 121 (7.27 mg, purity: 100%, yield: 21.04%). Compound 121 : ¹ H NMR (400 MHz, CDCl3) δ = 4.93 (s, 0.5 H), 4.79 (s, 0.5 H), 4.53 (dd, J=8.6, 1.6, 0.5 H), 4.28 (t, J=8.0, 0.5 H), 3.91 (d, 19 F ^NMR (376 MHz, CDCl3) δ = -88.87 (d, ¹³ C NMR (101 MHz, CDCl3) δ = 104.31, 84.94, 71.11, 55.20, 50.67, 48.68, 44.40, 43.08, 43.05, 40.40, 39.42, 39.31, 38.82, 36.40, 35.72, 33.50, 31.61, 30.17, 29.32, 29.25, 28.49, 25.48, 25.44, 24.39, 21.92, 20.98, 20.96, 20.87, 20.77, 20.75, 19.07, 18.98, 18.73, 12.37, 12.05, 11.90, 11.87. Example 123 Compound 123: Preparation of 4 -methylidene -5α- cholest -3β,25- diol

Step 1: Dissolve the reactant (5R)-5-[(1R,3aS,3bS,7S,9aR, 9bS,11aR)-7-acetyloxy-9a,11a-dimethyl-2,3,3a,3b,4,6, 7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-7 (500 mg, 1.124 mmol, 1.0 eq ) in tetrahydrofuran (40 mL). After cooling the reaction system to 0 ^o C, methylmagnesium chloride (3.75 mL, 11.24 mmol, 3 mol/L, 10 eq ) was slowly added and the reaction system was stirred at room temperature for 2 h. The reaction was monitored by TLC plate (petroleum ether: ethyl acetate = 5:1). The reaction was stopped when the raw material was consumed. 20 mL of water was added to the reaction system, extracted with ethyl acetate (50 mL×3), the organic phase was collected, dried with anhydrous sodium sulfate, and the organic phase was vacuum rotary dried to obtain a crude product. The crude product was dissolved in ethyl acetate and chromatographed by column chromatography (petroleum ether: ethyl acetate = 80:20) to obtain cholester-6(5)-ene-3β,4β,19,25-tetrol 123-1 (450 mg, purity: 90%, yield: 89.45%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.38 – 5.32 (m, 1H), 3.51 (dd, J = 11.6, 6.8 Hz, 1H), 2.33 – 2.19 (m, 2H), 2.06 – 1.92 (m, 2H), 1.88 – 1.78 (m, 3H), 1.63 – 1.46 (m, 6H), 1.42 – 1.31 (m, 4H), 1.27 (dd, J = 7.9, 4.1 Hz, 2H), 1.21 (s, 6H), 1.08 (ddd, J = 16.7, 13.5, 6.3 Hz, 5H), 1.01 (s, 3H), 0.93 (d, J = 6.6 Hz, 3H), 0.66 (d, J = 12.7 Hz, 3H).

Step 2: Cholest-6(5)-ene-3β,4β,19,25-tetrol 123-1 (450 mg, 1.118 mmol, 1.0 eq) was dissolved in dichloromethane (20 mL), and acetic anhydride (0.315 mL, 3.354 mmol, 3.0 eq), 4-dimethylaminopyridine (27.32 mg, 0.224 mmol, 0.2 eq) and triethylamine (0.777 mL, 5.590 mmol, 5.0 eq) were added in sequence. The mixture was stirred at room temperature for 3 hours and the reaction was monitored by TLC (petroleum ether: ethyl acetate = 5:1). After the reaction was completed, the reaction solution was quenched with methanol, washed once with saturated sodium bicarbonate (10 mL) and water (10 mL), dried over anhydrous sodium sulfate, concentrated, and then concentrated to dryness. Column chromatography (petroleum ether:ethyl acetate = 90:10) gave white solid acetate-(1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 123-2 (450 mg, purity: 90%, yield: 81.49%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.38 – 5.32 (m, 1H), 4.64-4.60 (m, 1H), 2.33 – 2.19 (m, 2H), 2.06 – 1.92 (m, 3H), 1.88 – 1.78 (m, 3H), 1.63 – 1.46 (m, 6H), 1.42 – 1.31 (m, 4H), 1.27 (dd, J = 7.9, 4.1 Hz, 2H), 1.21 (s, 6H), 1.08 (ddd, J = 16.7, 13.5, 6.3 Hz, 5H), 1.01 (s, 3H), 0.93 (d,J = 6.6 Hz, 3H), 0.66 (d, J = 12.7 Hz, 3H).

Step 3: Dissolve (1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6, 7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate 123-2 (450 mg, 1.012 mmol, 1.0 eq) in chloroform (20 mL) under nitrogen protection, add selenium dioxide (281 mg, 2.53 mmol, 2.5 eq) and N-methylmorpholine (307.07 mg, 3.036 mmol), the reaction mixture was heated to 75 degrees and stirred for 48 hours. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 3:1). The raw material basically disappeared. The reaction mixture was cooled to room temperature and quenched with water. The mixture was extracted with dichloromethane three times. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to dryness. The crude product was purified by rapid column chromatography (petroleum ether: ethyl acetate = 70:30) to obtain white solid acetic acid-(1R,3aS,3bS,6R,7S,9aR,9bS, 11aR)-6-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 123-3 (310 mg, 0.606 mmol, purity: 90%, yield: 59.85%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.75-5.70 (m, 1H), 4.80-4.70 (m, 1H), 4.28-4.23(m,1H), 2.33 – 2.19 (m, 2H), 2.06 – 1.92 (m, 3H), 1.88 – 1.78 (m, 3H), 1.63 – 1.46 (m, 6H), 1.42 – 1.31 (m, 4H), 1.27 (dd, J = 7.9, 4.1 Hz, 2H), 1.21 (s, 6H), 1.10-1.06 (m, 5H), 1.01 (s, 3H), 0.93 (d,J = 6.6 Hz, 3H), 0.66 (d, J = 12.7 Hz, 3H).

Step 4: Compound (1R,3aS,3bS,6R,7S,9aR, 9bS,11aR)-6-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate 123-3 (40 mg, 0.087 mmol, 1.0 eq) was dissolved in ethyl acetate (25 mL), and then platinum dioxide (30 mg, 0.13 mmol, 1.5 eq) was added and the reaction system was replaced with a hydrogen atmosphere. The reaction system was stirred at room temperature for 24 h. The reaction progress was monitored by TLC (petroleum ether: ethyl acetate = 3:1), and the starting material was consumed. The reaction system was filtered, and the organic phase was collected and concentrated to obtain a crude product. The crude product was chromatographed on a silica gel column (petroleum ether: ethyl acetate = 82: 18 to 81: 19) to obtain white solid acetic acid-(1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-6-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 123-4 (35 mg, purity 90%, yield 78.4%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.72 (dd, J = 8.2, 3.9 Hz, 1H), 3.83 (s, 1H), 2.09 (s, 3H), 1.93 (dd, J = 25.6, 12.8 Hz, 2H), 1.78 (t, J = 11.4 Hz, 4H), 1.67 (d, J = 12.4 Hz, 1H), 1.46 – 1.30 (m, 9H), 1.29 – 1.24 (m, 2H), 1.21 (s, 6H), 1.14 – 1.08 (m, 3H), 1.05 (s, 4H), 1.02 – 0.95 (m, 2H), 0.91 (d, J =6.5 Hz, 3H), 0.65 (s, 3H), 0.61 (s, 1H).

Step 5: Compound (1R,3aS,3bS,5aR,6R,7S, 9aR,9bS,11aR)-6-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate 123-4 (25 mg, 0.054 mmol) was dissolved in dichloromethane (5 mL). Under nitrogen protection, tetrapropylammonium perruthenate (5.69 mg, 0.016 mmol), N-methylmorpholine oxide (9.49 mg, 0.081 mmol) and 4A molecular sieve were added in sequence. The mixture was stirred at room temperature and the reaction was monitored by TLC (petroleum ether:ethyl acetate = 3:1). Water (10 mL) was added to the reaction system, and the aqueous layer was extracted with EA (3×25 mL). The ethyl acetate layers were combined and washed with saturated brine (3×10 mL). The ethyl acetate layer was dried over Na ₂ SO ₄ , filtered and concentrated to obtain a crude product. After the reaction was completed, the reaction solution was filtered, the filtrate was washed with water, the organic phase was dried and concentrated, and the crude product was purified by rapid column chromatography (petroleum ether: ethyl acetate = 81:19) to obtain white solid acetate-(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-6-oxyylidene hexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 123-5 (25 mg, purity 90%, yield 90%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.16 (dd, J = 12.2, 7.4 Hz, 1H), 2.22 (dd, J = 19.4, 6.6 Hz, 2H), 2.15 (s, 3H), 2.02 – 1.71 (m, 5H), 1.60 (dd, J = 18.1,14.5 Hz, 3H), 1.46 – 1.24 (m, 11H), 1.21 (s, 6H), 1.14 – 1.00 (m, 4H), 0.92 (d, J = 6.5 Hz, 3H), 0.75 (s, 3H), 0.65 (s, 3H).

Step 6: In a 50 mL round-bottom flask, methyltriphenylphosphonium bromide (4.65 g, 13.02 mmol) was suspended in tetrahydrofuran (50 mL) at room temperature, and 1M/L potassium tert-butoxide tetrahydrofuran solution (13.02 mL, 13.02 mmol) was added dropwise at 0°C. The mixture was stirred at room temperature for 2 hours, and then acetic acid-(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-6-oxyylidene hexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 123-5 (1.2 g, 2.60 mmol) in tetrahydrofuran (10 mL), and the mixture was stirred at room temperature for 3 hours. TLC (petroleum ether/ethyl acetate = 10/1) was used to monitor the reaction. After the reaction was completed, water (50 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (40 mL×3). The extracted organic solution was washed with saturated brine (80 mL), dried with anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified and separated by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 10/1) to give white solid acetate-(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 123-6 (612 mg, purity: 95%, yield: 48.66%). ¹ H NMR (400 MHz, CDCl3) δ = 5.11 (dd, J=11.8, 5.3, 1H), 4.86 (s, 1H), 4.59 (s, 1H), 2.12 (s, 3H), 2.04 – 1.24 (m, 24H), 1.21 (s, 6H), 1.16 – 1.00 (m, 5H), 0.92 (d, J=6.6, 3H), 0.71 (s, 3H), 0.65 (s, 3H).

Step 7: In a 50 mL round-bottom flask at room temperature, (1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate 123-6 (700 g, 1.53 mmol) was dissolved in tetrahydrofuran (10 mL) and methanol (10 mL), and lithium hydroxide, monohydrate (385 mg, 9.16 mmol) and water (5 mL) were added at room temperature, followed by stirring at room temperature for 1 hour, and the reaction was monitored by TLC (petroleum ether:ethyl acetate = 4:1). After the reaction was completed, the mixture was diluted with water (30 mL), extracted with ethyl acetate (30 mL×3), the organic phase was washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain white solid 4-methylidene-5α-cholestane-3β,25-diol 123 (614 mg, purity: 97%, yield: 93.67%). Compound 123 : ¹ H NMR (400 MHz, CDCl ₃ ) δ = 5.04 (s, 1H), 4.63 (s, 1H), 3.99 (dd, J=11.4, 5.4, 1H), 1.99 (ddd, J=11.8, 8.5, 3.3, 2H), 1.89 – 1.27 (m, 23H), 1.21 (s, 6H), 1.14 – 1.00 (m, 5H), 0.92 (d, J=6.5, 3H), 0.69 (s, 3H), 0.65 (s, 3H). ¹³ C NMR (101 MHz, CDCl 3 ) δ = 153.33, 102.35, 73.37, 71.13, 56.28, 56.24, 54.49, 49.90, 44.42, 42.62, 40.08, 38.61, 37.27, 36.43, 35.76, 35.26, 33.05, 31.61, 29.36, 29.21, 28.28, 24.27, 24.21, 21.72, 20.78, 18.63, 12.93, 12.07. LC-MS: [M+H-2H ₂ O] ⁺ = 381.3. Example 137 : Compound 137 : Preparation of 24-[ Hydroxy (2- methoxyphenyl ) methyl ]-7- methyl -5α- cholane- 3β,4β- diol

Step 1: Dissolve (9R)-9-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-2,2,5a,7a-tetramethyl-11-methylidene-4,5,5a,5b,6, 7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladecane 106-5 (25 mg, 0.038 mmol) in methanol (5 mL) Pd/C (13 mg, 0.061 mmol) was added, the system was replaced with hydrogen, and the mixture was stirred at 40°C for 1 hour. The mixture was filtered through celite overnight and rotary dried to obtain the crude product 137-1 (20 mg), which was directly used in the next step.

Step 2: Dissolve (9R)-9-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-2,2,5a,7a,11-pentamethyl-4,5,5a,5b,6,7, 7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladecane 137-1 (20 mg, 0.030 mmol) in tetrahydrofuran (2 mL) , hydrochloric acid (1 mL, 3.000 mmol) was added, and the mixture was reacted at 40°C for 2 hours. Water was added to the reaction solution, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and rotary dried. The crude product was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 1/1) to obtain 24-[hydroxy(2-methoxyphenyl)methyl]-7-methyl-5α-cholane-3β,4β-diol as a white solid 137 (4.5 mg, 0.007 mmol, 17.32%, yield for two steps). Compound 137 : ¹ H NMR (400MHz, CDCl ₃ ) δ 7.32 – 7.27 (m, 1H), 7.25 – 7.21 (m, 1H), 6.95 (t, J = 7.4Hz, 1H), 6.88 (d, J = 8.2Hz, 1H), 4.85 (dt, J = 9.6, 5.8Hz, 1H), 3.86 (s, 3H), 3.71 (d, J = 2.2Hz, 1H), 3.68 – 3.64 (m, 0H), 3.60 – 3.51 (m, 1H), 1.96 (d, J = 13.0Hz, 1H), 1.74 (dd, J = 15.3, 5.3Hz, 4H), 1.67 – 1.60 (m, 4H), 1.54 (dd, J = 20.4, 7.7 Hz, 3H), 1.49 – 1.42 (m, 2H), 1.41 – 1.30 (m, 5H), 1.27 (d, J = 12.7 Hz, 3H), 1.13 – 1.05 (m, 4H), 1.03 (s, 1H), 1.00 (d, J = 6.0 Hz, 3H), 0.98 (s, 3H), 0.92 – 0.87 (m, 3H), 0.66 – 0.62 (m, 3H). LC-MS: [M+HH ₂ O] ⁺ = 477.50. Example 138 : Compound 138 : Preparation of (1R,3aS,3bS,7S,9aR,9bS,11aR)-1-[(2R)-5,5 -difluoro -6- hydroxy -6- methylhept -2- yl ]-4,4 -difluoro -7- hydroxy - 9a,11a -dimethylhexahydro -1H- cyclopenta [1,2-a] phenanthrene -6 -one

Step 1: Dissolve compound (1R,3aS,3bS,6R,7S,9aR,9bS, 11aR)-7-(benzyloxy)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-4,4-difluoro-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-ol 94-7 (110 mg, 0.189 mmol, 1 eq) in dichloromethane (5 mL), slowly add Dess-Martin periodinane (160 mg, 0.378 mmol, 2 eq), stir at room temperature for 3 hours, and monitor by TLC (petroleum ether: ethyl acetate = 4:1). After the reaction was completed, water was added to destroy the reaction mixture, and then the mixture was extracted with ethyl acetate (50 mL). The organic phase was washed twice with saturated brine, dried over anhydrous sodium sulfate, filtered, and rotary dried to obtain a crude product. The crude product was separated and purified by flash chromatography (petroleum ether: ethyl acetate = 100: 0 to 3: 1) to obtain (1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-7-(benzyloxy)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-4,4-difluoro-9a, 11a-dimethylhexahydro-1H-cyclopenta[1,2-a]phenanthrene-6-one as a white solid 138-1 (109 mg, Purity: 97%, yield: 73%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.12 – 8.05 (m, 2H), 7.58 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 5.44 (dd, J = 11.9, 7.5 Hz, 1H), 2.63 (d, J = 13.8 Hz,1H), 2.42 (s, 1H), 2.14 – 1.99 (m, 6H), 1.96 – 1.82 (m, 4H), 1.79 – 1.60 (m, 7H), 1.49 (dd, J = 11.0, 6.9 Hz, 3H), 1.36 (d, J = 5.9 Hz, 5H), 1.31 (s, 6H), 1.29 (s, 2H), 0.95 (d, J = 6.5 Hz, 3H), 0.85 (s, 3H), 0.69 (s, 3H).

Step 2: At room temperature, (1R,3aS,3bS,7S,9aR,9bS, 11aR)-7-(benzyloxy)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-4,4-difluoro-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-one 138-1 (15 mg, 0.025 mmol, 1.0 eq) was dissolved in tetrahydrofuran (0.5 mL) and methanol (0.5 mL). Lithium hydroxide monohydrate (11 mg, 0.25 mmol, 10.0 eq) and water (0.2 mL) were added at room temperature, followed by stirring at room temperature for 30 min. TLC The reaction was monitored by HPLC (petroleum ether: ethyl acetate = 10:1). After the reaction was completed, the mixture was diluted with water (10 mL), extracted with ethyl acetate (10 mL×2), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and the organic phase was concentrated. The crude product was separated and purified by flash chromatography (petroleum ether: ethyl acetate = 100: 0 to 3: 1) to obtain (1R, 3aS, 3bS, 7S, 9aR, 9bS, 11aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-4,4-difluoro-7-hydroxy-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-one 138 (6.2 mg, purity 100%, yield 52%) as a white solid. Compound 138 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.15 (t, J = 8.2 Hz, 1H), 3.49 (d, J = 3.4 Hz, 1H), 2.55 – 2.42 (m, 2H), 2.11 (d, J = 8.9 Hz, 1H), 2.02 (d, J = 12.5 Hz, 2H), 1.91 (d, J = 13.0 Hz, 2H), 1.84 (d, J = 5.5 Hz, 1H), 1.73 (s, 2H), 1.67 (s, 1H), 1.62 (d, J = 11.8 Hz, 2H), 1.55 (d, J = 9.3 Hz, 2H), 1.48 (d, J = 7.5 Hz, 2H), 1.37 (s, 1H), 1.33 (s, 1H), 1.31 (s, 6H), 1.29 (s, 2H), 1.15 (t, J = 9.3 Hz, 2H), 0.94 (d, J = 6.5 Hz, 3H), 0.88 (t, J = 6.7 Hz, 1H), 0.77 (s, 3H), 0.69 (d, J = 7.5 Hz, 3H). ¹⁹ F NMR (377 MHz, CDCl ₃ ) δ -90.22, -90.85, -111.49, -112.12, -115.16, -115.81, -116.09, -116.74. LC-MS: [MH] ⁺ = 489.35. Example 139 : Compound 139 : Preparation of (1R, 3aR, 7S, 9aR, 9bR, 11aR)-1-[(2R)-5,5 -difluoro -6- hydroxy -6 - methylhept -2- yl ]-4- fluoro -9a, 11a -dimethyl -2,3,3a, 5,5a, 6,7,8,9,9a,9b, 10,11,11a- tetradecahydro -1H- cyclopenta [1,2-a] phenanthrene -6,7- diol

Step 1: At room temperature, (3S, 4R, 5R, 8S, 9S, 10R, 13R, 14S, 17R)-17-((R)-6-acetyloxy-5,5-difluoro-6-methylheptane-2-yl)-10,13-dimethyl-7-oxohexadecahydro-1H-cyclopentadienyl[a]phenanthrene-3,4-diyl diacetate 94-4 (53 mg, 0.089 mmol) was dissolved in diethylaminosulfur trifluoride (2 mL), stirred at 70°C for 2 hours, and the reaction was monitored by TLC (petroleum ether: ethyl acetate = 4:1). After the reaction was completed, the reaction solution was diluted with ethyl acetate and slowly added dropwise to ice water (20 mL) for quenching. The mixture was extracted with ethyl acetate (15 mL×2), and the organic phase was saturated with brine (20 The reaction mixture was washed with 4% paraformaldehyde (20% ethyl acetate) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 10:1) to obtain white solid acetate-(6R)-6-[(1R,3aR,5aR,6R, 7S,9aR,9bR,11aR)-6,7-diethoxy-4-fluoro-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-3,3-difluoro-2-methylhept-2-yl ester 139-1 (4.5 mg, purity: 90%, yield: 8.2%).

Step 2: At room temperature, the obtained white solid (6R)-6-[(1R,3aR,5aR,6R,7S,9aR,9bR,11aR)-6,7-diethoxy-4-fluoro-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-3,3-difluoro-2-methylhept-2-yl acetate 139-1 (45 mg, 0.073 mmol, 1.0 eq) was dissolved in tetrahydrofuran (1 mL) and methanol (1 mL). Lithium hydroxide monohydrate (15 mg, 0.365 mmol, 5.0 eq) and water (0.5 mL), then stirred at room temperature for 30 min, the reaction was monitored by TLC (petroleum ether: ethyl acetate = 10:1), after the reaction was completed, it was diluted with water (10 mL), extracted with ethyl acetate (10 mL × 2), the organic phase was saturated with brine (20 The reaction mixture was washed with 4% paraformaldehyde (2% ethyl acetate) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 2:1) to obtain a white solid (1R,3aR,5aR,6R,7S,9aR,9bR,11aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-4-fluoro-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6,7-diol 139-2 (28 mg, purity: 90 %, yield: 77.78%).

Step 3: (1R,3aR,5aR,6R,7S,9aR, 9bR,11aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-4-fluoro-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6,7-diol 139-2 (28 mg, 0.057 mmol, 1.0 eq) was dissolved in dichloromethane (2 mL) and tetrahydrofuran (1 mL) at room temperature. Triethylamine (35 mg, 0.34 mmol, 6.0 eq) and 4-dimethylaminopyridine (7 mg, 0.057 mmol, 1.0 eq) were added at room temperature. mmol, 1.0 eq) and benzoyl chloride (24 mg, 0.17 mmol, 3.0 eq), then stirred at room temperature for 8 hours, the reaction was monitored by TLC (petroleum ether: ethyl acetate = 1:1), after the reaction was completed, quenched with water (10 mL), extracted with ethyl acetate (10 mL × 2), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) and SFC (Instrument: Waters Acquity UPCC, Column: Daicel CHIRALPAK IC_3, 3.0*150mm, 3um, Mobile Phase: A/B: CO2/MeOH (0.1%DEA) = 50/50, Flow rate: 1.5 ml/min , Column Temp: 37 degree ) to give a white solid (benzoic acid-(1R,3aR,5aR,6R,7S,9aR,9bR,11aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-4-fluoro-6-hydroxy-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 139-3 (15 mg, purity: 95%, yield: 44.12%, retention time t _R =1.624 min). ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.04 (d, J = 8.1 Hz, 2H), 7.58 (t, J = 7.2 Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 4.99 (dd, J = 8.3, 3.6 Hz, 1H), 3.98 (s,1H), 2.25 (dd, J = 34.8, 4.1 Hz, 1H), 2.08 – 1.95 (m, 3H), 1.89 – 1.71 (m, 9H), 1.59 – 1.44 (m, 6H), 1.31 (s, 6H), 1.26 (s, 1H), 1.17 (d, J = 13.4 Hz,2H), 1.14 (s, 3H), 1.02 (t, J = 10.2 Hz, 1H), 0.95 (d, J = 6.5 Hz, 3H), 0.69 (s, 3H).

Step 4: (1R,3aR,7S,9aR,9bR,11aR)-7-(benzyloxy)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-4-fluoro-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-ol 139-3 (15 mg, 0.025 mmol, 1.0 eq) was dissolved in tetrahydrofuran (0.5 mL) and methanol (0.5 mL) at room temperature. Lithium hydroxide monohydrate (11 mg, 0.25 mmol, 10.0 eq) and water (0.2 mL), then stirred at room temperature for 30 min, the reaction was monitored by TLC (petroleum ether: ethyl acetate = 10:1), after the reaction was completed, it was diluted with water (10 mL), extracted with ethyl acetate (10 mL×2), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and the crude product was separated and purified by flash chromatography (petroleum ether: ethyl acetate = 100: 0 to 3: 1) to obtain (1R,3aR,7S,9aR,9bR,11aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylhept-2-yl]-4-fluoro-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9, 9a,9b,10,11,11a-Tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-6,7-diol was obtained as a white solid 139 (10 mg, purity 100%, yield 79%). Compound 139 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.85 (s, 1H), 3.60 (d, J = 11.0 Hz, 1H), 2.66 (t, J = 12.4 Hz, 1H), 2.14 (s, 1H), 2.01 (t, J = 11.5 Hz, 3H), 1.89 (s, 2H), 1.85(d, J = 4.1 Hz, 1H), 1.77 (s, 2H), 1.71 (s, 1H), 1.63 – 1.55 (m, 4H), 1.47 – 1.44 (m, 2H), 1.37 (s, 1H), 1.33 (s, 1H), 1.30 (s, 6H), 1.28 (s, 2H), 1.13 – 1.08 (m, 2H), 1.05 (s, 3H), 0.95 (d, J = 6.5 Hz, 3H), 0.88 (t, J = 6.6 Hz, 1H), 0.65 (s, 3H). ¹⁹ F NMR (377 MHz, CDCl ₃ ) δ -109.66, -115.15, -115.80, -116.12, -116.77. LC-MS: [MH] ⁺ = 471.35. Example 143 : Compound 143: Preparation of 7- amino -24-[ hydroxy (2- methoxyphenyl ) methyl ]-5α- cholane- 3β,4β- diol

Step 1: Compound (3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7, 7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta-11-one 106-4 (50 mg, 0.075 mmol, 1.0 eq) was dissolved in a mixed solvent of tetrahydrofuran (2 mL) and methanol (1 mL), and catalytic amounts of acetic acid (0.001 mL, 0.014 mmol) and ammonium acetate (57.81 mg, 0.750 mmol, 10 eq) were added. The resulting mixture was stirred in the reaction solution under N2 at 25°C for 1 h, followed by the addition of sodium cyanoborohydride [reducing agent] (47.13 mg, 0.750 mmol, 10 eq). The stirring was continued for 2 hours, and the progress of the reaction was monitored by TLC plate (dichloromethane: methanol = 10:1). The mixture was quenched with water, and the aqueous layer was extracted with dichloromethane (3×10 mL). The dichloromethane layers were combined and washed with saturated brine (5 mL), dried over anhydrous Na2SO4, filtered and concentrated to obtain a crude product, which was purified by silica gel column chromatography (dichloromethane:methanol=10:1) to obtain a white solid (3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a, 8,9,10,10a,10b,11,12,12a,12b-Hexadecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[11-amine 143-1 (30 mg, purity: 90%, yield: 56.87%). LC-MS: [M+H] ⁺ = 668.4.

Step 2: Compound (3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a, 8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta-11-amine 143-1 (30 mg, 0.05 mmol, 1.0 eq) was dissolved in tetrahydrofuran (5 mL), diluted hydrochloric acid (0.05 mL) was added, stirred at 25 °C for 1 hour, and then continued to stir for 2 hours. The reaction progress was monitored by TLC (dichloromethane: methanol = 5:1). Water was added to quench, and the aqueous layer was extracted with dichloromethane (3×10 mL). The dichloromethane layers were combined and washed with saturated brine (5 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (dichloromethane: methanol = 10:1) to obtain white solid 7-amino-24-[hydroxy(2-methoxyphenyl)methyl]-5α-cholane-3β,4β-diol 143 (17.79 mg, 0.034 mmol, purity: 97.15%, yield: 74.92%). Compound 143: ¹ H NMR (400 MHz, DMSO) δ 7.55 (s, 1H), 7.38 (m, 1H), 7.18 (t, J = 7.8 Hz, 1H), 6.92 (m, 2H), 4.86 (s, 2H), 4.42 (d, J = 5.8 Hz, 1H), 4.17 (t, J = 6.3 Hz, 1H),3.75 (d, J = 3.0 Hz, 3H), 3.44 (d, J = 22.4 Hz, 1H), 3.26 (m, 1H), 1.94 (dd, J = 27.6, 11.7 Hz, 2H), 1.75 (m, 3H), 1.59 (t, J = 12.9 Hz, 4H), 1.43 (s, 5H), 1.25 (m,7H), 1.00 (s, 6H), 0.96 (s, 4H), 0.86 (d, J = 5.8 Hz, 3H), 0.61 (d, J = 2.5 Hz, 3H). LC-MS: [M+H] ⁺ = 427.3. Example 144 : Compound 144: Preparation of 4- methyl -5α- cholestane -3β,25- diol

Step 1: Dissolve (3S,5R,8S,9S,10R,13R,14S,17R)-17-((R)-6-hydroxy-6-methylheptane-2-yl)-10,13-dimethyl-4-methylenehexahydro-1H-cyclopenta[a]phenanthrene-3-ol 123 (25 mg, 0.060 mmol, 1 eq ) in dichloromethane (2 mL) at room temperature, add DMAP (2 mg, 0.016 mmol, 0.3 eq ) and triethylamine (36 mg, 0.36 mmol, 6 eq ), cool to 0 ^o C in an ice bath, and slowly add a solution of acetic anhydride (12 mg, 0.12 mmol, 2 eq ) in dichloromethane (0.5 mL) dropwise. After 10 minutes, warm to room temperature and stir for 6 hours. The reaction solution was quenched with water and extracted with dichloromethane (10 mL x 2). The organic phases were combined and washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was separated by chromatography (4 g, 0-10% EtOAc/PE, 20 mL/min) to obtain (R)-6-((3S, 5R, 8S, 9S, 10R, 13R, 14S, 17R)-3-acetyloxy-10,13-dimethyl-4-methylenedecahedral-1H-cyclopentylphenanthren-17-yl)-2-methylhept-2-yl acetate 144-1 (10 mg, purity: 90%, yield 43.3%). ¹ H NMR (400 MHz, CDCl3) δ 5.11 (d, J = 6.7 Hz, 1H), 4.86 (s, 1H), 4.59 (s, 1H), 2.12 (s, 3H), 2.05 – 1.89 (m, 3H), 1.77 (dd, J = 27.1, 12.6 Hz, 5H), 1.56 (d, J = 12.7 Hz, 3H), 1.47 – 1.31 (m, 10H), 1.21 (s, 6H), 1.09 (dd, J = 24.8, 14.8 Hz, 5H), 0.92 (d, J = 6.3 Hz, 3H), 0.88 – 0.76 (m, 2H), 0.71 (s, 3H), 0.65 (s, 3H).

Step 2: (R)-6-((3S,5R,8S,9S,10R,13R,14S,17R)-3-acetyloxy-10,13-dimethyl-4-methylenedecanoyl-1H-cyclopentylphenanthren-17-yl)-2-methylhept-2-yl acetate 144-1 (10 mg, 0.020 mmol, 1 eq) was dissolved in ethyl acetate (3 mL) at room temperature, 10% Pd/C (20 mg) and acetic acid (0.1 mL) were added, and the mixture was stirred in a hydrogen atmosphere at room temperature for 16 hours. The reaction was monitored by HNMR. After the reaction was completed, the reaction solution was diluted with ethyl acetate (10 mL), filtered through diatomaceous earth, and the filtrate was washed with saturated sodium bicarbonate solution (10 mL) and saturated salt water (10 mL) in sequence, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a white solid (6R)-6-((3S, 5S, 8S, 9S, 10R, 13R, 14S, 17R)-3-acetyloxy-4,10,13-trimethylhexahydro-1H-cyclopentadienylphenanthren-17-yl)-2-methylheptane-2-yl acetate 144-2 (5 mg, purity: 90%, yield: 44.8%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.89 – 4.27 (m, 1H), 2.10 (s, 1H), 2.04 (d, J = 4.5 Hz, 1H), 1.97 (s, 1H), 1.71 (d, J = 10.9 Hz, 3H), 1.42 (d, J = 3.9 Hz, 6H), 1.04 (dd, J = 15.6, 9.8 Hz, 7H), 0.85 (ddd, J = 20.0, 11.2, 5.5 Hz, 11H), 0.64 (d, J = 4.9 Hz, 3H).

Step 3: (6R)-6-((3S, 5S, 8S, 9S, 10R, 13R, 14S, 17R)-3-acetyloxy-4,10,13-trimethylhexadecahydro-1H-cyclopentadienylphenanthren-17-yl)-2-methylheptane-2-yl acetate 144-2 (5 mg, 0.010 mmol, 1.0 eq) was dissolved in tetrahydrofuran (0.5 mL) and methanol (0.5 mL) at room temperature, and lithium hydroxide monohydrate (8 mg, 0.19 mmol, 19.2 eq) and water (0.2 mL) were added at room temperature, followed by stirring at room temperature for 2 h and 60 ^°C. C oil bath for 3 hours, and the reaction was detected by TLC plate (petroleum ether: ethyl acetate = 4:1, phosphomolybdic acid baking plate). After the reaction was completed, it was diluted with water (10 mL), extracted with ethyl acetate (10 mL×2), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, concentrated the organic phase, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain white solid 4-methyl-5α-cholestane-3β,25-diol 144 (3.07 mg, purity: 99.6%, yield: 38.3%). Compound 144 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.79 – 2.95 (m, 1H), 1.95 (d, J = 12.7 Hz, 1H), 1.82 – 1.66 (m, 3H), 1.58 (d, J = 8.3 Hz, 4H), 1.48 – 1.32 (m, 10H), 1.27 (d, J = 12.2 Hz, 3H), 1.21 (s, 6H), 1.12 – 0.98 (m, 5H), 0.96 – 0.87 (m, 7H), 0.83 (d, J = 6.3 Hz, 3H), 0.80 – 0.67 (m, 1H), 0.64 (d, J = 4.9 Hz, 3H), 0.62 – 0.55 (m, 1H). Examples 158 & 159 : Compound 158 [(1R, 3aS, 3bS, 4Z, 6R, 7S, 9aR, 9bS, 11aR)-6,7 -dihydroxy -1-[(2R)-6- hydroxy -6-(2- methoxyphenyl ) hexan -2- yl ]-9a, 11a -dimethylhexadecahydro -1H - cyclopenta [1,2-a] phenanthrene -4- ylidene ] acetonitrile and Compound 159 Preparation of [(1R,3aS,3bS,6R,7S,9aR,9bS,11aR)-6,7 -dihydroxy -1-[(2R)-6- hydroxy -6-(2- methoxyphenyl ) hexan -2- yl ]-9a,11a- dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -4- yl ] acetonitrile .

Step 1: In an ice-water bath, n-butyl lithium (0.180 mL, 0.450 mmol) solution was added dropwise to a solution of diethyl cyanomethylphosphonate (87.63 mg, 0.495 mmol) in tetrahydrofuran (5 mL). After stirring for 30 minutes, (3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxodadecan-3-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9, 10,10a,10b,11,12, 12a,12b-Hexadecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[11-one] 106-4 (30 mg, 0.045 mmol) was dissolved in tetrahydrofuran and added dropwise to the reaction flask. The mixture was stirred at room temperature for 2 hours. The reaction solution was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and rotary dried to obtain a crude product. The crude product was purified by flash chromatography (petroleum ether/ethyl acetate = 8%) to obtain [(3aS,5aR,5bS,7aR,8R,10aS,10bS, 11Z,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8, 9,10,10a,10b,11,12,12a,12b-Hexadecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[11-ylidene]acetonitrile Colorless transparent solid 159-1 (45 mg, 61.62%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.45 (d, J = 7.6 Hz, 1H), 7.18 (s, 1H), 6.95 (d, J = 7.4 Hz, 1H), 6.81 (d, J = 8.2 Hz, 1H), 5.14 – 4.99 (m, 2H), 4.12 (d, J = 7.1 Hz, 1H), 4.07 – 3.97 (m, 1H), 3.81 (s, 3H), 2.83 (dd, J = 12.8, 2.4 Hz, 1H), 2.44 (s, 1H), 2.28 (s, 1H), 2.02 (d, J = 13.0 Hz, 1H), 1.93 – 1.77 (m, 4H), 1.73 – 1.59 (m, 3H), 1.52 (s, 4H), 1.42 (ddd, J = 23.0, 18.0, 9.9 Hz, 7H), 1.32 (s, 3H), 1.26 (dd, J = 6.3, 3.5 Hz, 3H), 1.21 (s, 3H), 1.09 (d, J = 8.8 Hz, 2H), 1.06 – 0.96 (m, 3H), 0.89 (s, 9H), 0.82 (dd, J = 12.0, 7.0 Hz, 2H), 0.67 (d, J = 6.0 Hz, 3H), 0.02 (t, J = 3.0 Hz, 3H), -0.14 (s, 3H).

Step 2: Dissolve [(3aS,5aR,5bS,7aR,8R,10aS,10bS,11Z, 12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10, 10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[11-ylidene]acetonitrile 159-1 (40 mg, 0.058 mmol) in methanol (5% ethanol). mL), add Pd/C (20 mg, 0.094 mmol), replace with hydrogen, and stir the mixture at 40°C for 2 hours. TLC (petroleum ether/ethyl acetate = 5/1) tracking the reaction solution found that the raw material had reacted completely and there was a new point with increased polarity. Filter Pd/C through diatomaceous earth and spin dry. The crude product was purified by flash chromatography (petroleum ether/ethyl acetate = 10%) to obtain [(3aS,5aR,5bS,7aR,8R,10aS,10bS,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11, 12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[11-yl]acetonitrile 159-2 as a white solid (20 mg, 42.35%). ¹ H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.6 Hz, 1H), 7.32 (s, 1H), 7.09 (d, J = 7.4 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 5.26 – 5.16 (m, 1H), 4.20 – 4.07 (m, 2H), 3.95 (s, 3H), 2.69 (s, 2H), 2.14 (d, J = 12.6 Hz, 1H), 2.02 – 1.78 (m, 7H), 1.70 (d, J = 15.0 Hz, 6H), 1.65 (s, 3H), 1.57 (s, 1H), 1.55 – 1.46 (m, 5H), 1.45 (s, 3H), 1.41 (d, J = 12.9 Hz, 3H), 1.34 – 1.23 (m, 3H), 1.18 (s, 3H), 1.13 (dd, J = 16.0, 8.1 Hz, 2H), 1.03 (s, 9H), 0.99 (s, 2H), 0.83 (d, J = 5.8 Hz, 3H), 0.16 (s, 3H), -0.00 (s, 3H).

Step 3: Dissolve [(3aS,5aR,5bS,7aR,8R,10aS,10bS, 12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a, 10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[11-yl]acetonitrile 159-2 (35 mg, 0.051 mmol) in tetrahydrofuran (3 mL), hydrochloric acid (2 mL, 6.000 mmol) was added, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction solution, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and rotary dried. The crude product was purified by flash chromatography (petroleum ether/ethyl acetate = 50%) to obtain [(1R,3aS,3bS,6R,7S,9aR,9bS,11aR)-6,7-dihydroxy-1-[(2R)-6-hydroxy-6-(2-methoxyphenyl)hexan-2-yl]-9a,11a-dimethylhexahydro-1H-cyclopenta[1,2-a]phenanthrene-4-yl]acetonitrile 159 (5 mg, 0.008 mmol, 15.63%) as a white solid.

Compound 159 : ¹ H NMR (400 MHz, CDCl3) δ 7.31 – 7.27 (m, 1H), 7.26 – 7.21 (m, 1H), 6.96 (t, J = 7.4 Hz, 1H), 6.88 (d, J = 8.2 Hz, 1H), 4.89 – 4.80 (m, 1H), 3.86 (s, 3H), 3.74 (s, 1H), 3.56 (d, J = 10.7 Hz, 1H), 2.54 (d, J = 4.5 Hz, 2H), 1.99 (d, J = 12.1 Hz, 2H), 1.86 (t, J = 10.0 Hz, 2H), 1.76 (d, J = 10.3 Hz, 3H), 1.69 – 1.63 (m, 3H), 1.51 (dd, J = 12.3, 7.2 Hz, 3H), 1.43 – 1.32 (m, 6H), 1.27 (d, J = 12.7 Hz, 3H), 1.10 (dd, J = LCMS (ESI) [M+HH ₂ O] ⁺ = 520.45, t _R = 6.941 min.

Step 4: Dissolve [(3aS,5aR,5bS,7aR,8R,10aS,10bS,11Z, 12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9, 10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[11-ylidene]acetonitrile 159-1 (40 mg, 0.058 mmol) in tetrahydrofuran (3 mL), hydrochloric acid (2 mL, 6.000 mmol) was added, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction solution, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate. The crude product was purified by flash chromatography (petroleum ether/ethyl acetate = 50%) to obtain [(1R,3aS,3bS,4Z,6R,7S,9aR,9bS,11aR)-6,7-dihydroxy-1-[(2R)-6-hydroxy-6-(2-methoxyphenyl)hexan-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-4-ylidene]acetonitrile 158 (15 mg, 0.024 mmol, 42.03%) as a white solid. Compound 158 : ¹ H NMR (400 MHz, CDCl3) δ 7.33 – 7.27 (m, 1H), 7.26 – 7.20 (m, 1H), 6.96 (t, J = 7.5 Hz, 1H), 6.89 (d, J = 8.2 Hz, 1H), 5.06 (s, 1H), 4.85 (dt, J = 9.6, 5.8 Hz, 1H), 3.86 (s, 4H), 3.62 – 3.52 (m, 1H), 2.73 (dd, J = 12.7, 2.3 Hz, 1H), 2.55 (t, J = 13.0 Hz, 1H), 2.24 (t, J = 10.9 Hz, 1H), 2.01 (d, J = 12.6 Hz, 2H), 1.85 (d, J = 6.6 Hz, 2H), 1.78 – 1.67 (m, 4H), 1.43 (dd, J = 15.2, 4.9 Hz, 5H), 1.32 – 1.22 (m, 4H), 1.19 13 ^C NMR (101 MHz, CDCl ₃ ) δ 156.57, 132.56, 128.27, 127.01, 126.88, 120.76, 117.66, 110.57, 90.13, 74.06, 71.84, 71.35, 70.95, 56.44, 55.28, 54.96, 51.72, 49.47, 43.80, 42.94, 38.33, 37.74, 37.55, 36.48, 36.28, 35.99, 35.79, 35.61, 35.47, 35.40, 31.54, 28.06, 25.64, 25.07, 22.70, 22.56, 18.74, 12.13, -0.01. LCMS (ESI) [M+H-2H ₂ O] ⁺ = 500.37, t _R = 5.860 min. Example 160 : Compound 160 Preparation of 25- hydroxy -4β- hydroxy -3β - hydroxy -5α- cholest -7- carbonitrile .

Step 1: Dissolve (5R)-5-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12aR,12bR)-2,2,5a,7a-tetramethyl-11-oxyde-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]hexanoic acid methyl ester I-12 (200 mg, 0.421 mmol, 1 eq) in methanol (5 mL) at room temperature and cool to 0 ^°C under nitrogen. C, sodium borohydride (24 mg, 0.632 mmol, 1.5 eq) was added, and then the mixture was stirred at room temperature for 2 hours. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 2: 1). After the reaction was completed, the mixture was quenched with water (30 mL), extracted with ethyl acetate (30 mL×2), the organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and the organic phase was rotary dried to obtain a white solid (5R)-5-[(3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR, 12bR)-11-hydroxy-2,2,5a,7a-tetramethyl-4,5,5a, 5b, 6, 7, 7a, 8, 9, 10, 10a, 10b,11,12,12a,12b-hexadecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]hexanoic acid methyl ester 160-1 (200 mg, purity: 95%, yield: 99%) was directly used for the next step.

Step 2: At room temperature, (5R)-5-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12aR,12bR)-11-hydroxy-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]hexanoic acid methyl ester 160-1 (200 mg, 0.42 mmol) was dissolved in anhydrous tetrahydrofuran (5 mL). The mixture was cooled to 0 ^° C under nitrogen atmosphere and methylmagnesium bromide (3 M in ) was added dropwise. 2-Me-THF, 0.86 mL, 4.19 mmol, 10 eq), then stirred at room temperature for 2 hours, monitored by TLC (petroleum ether: ethyl acetate = 2: 1), after the reaction was completed, the system was cooled to 0 ^o C, quenched with saturated aqueous ammonium chloride solution (30 mL), extracted with ethyl acetate (30 mL × 2), the organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4: 1) to obtain a white solid (3aS, 5aR, 5bS, 7aR, 8R, 10aS,10bS,12aR,12bR)-8-[(2R)-6-hydroxy-6-methylhept-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a, 10b,11,12,12a,12b-hexadecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxolanecyclopentan-11-ol 160-2 (139 mg, purity: 95 %, yield: 67 %). ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.05 – 3.92 (m, 3H), 1.98 – 1.89 (m, 2H), 1.80 (dd, J = 14.1, 7.2 Hz, 3H), 1.75 – 1.54 (m, 6H), 1.48 – 1.33 (m, 13H), 1.30(s, 3H), 1.27 (dd, J = 9.8, 2.6 Hz, 4H), 1.21 (s, 6H), 1.19 – 1.10 (m, 4H), 1.05 (d, J = 7.6 Hz, 3H), 0.92 (d, J = 6.5 Hz, 3H), 0.68 (d, J = 8.2 Hz, 3H).

Step 3: (3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR,12bR)-8-[(2R)-6-hydroxy-6-methylhept-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxolanecyclopentane-11-ol 160-2 (130 mg, 0.273 mmol, 1.0 eq) was dissolved in tetrahydrofuran (10 mL), desmartine oxidant (424 mg, 0.545 mmol, 2 eq) was added at room temperature, and then stirred at room temperature for 1 hour. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction was completed, ice water (50 mL) was used for quenching, and ethyl acetate (30 mL×2) was used for extraction. The organic phase was saturated with brine (50 The mixture was washed with 1% paraformaldehyde and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain a white solid (3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12aR, 12bR)-8-[(2R)-6-hydroxy-6-methylhept-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7, 7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta-11-one 160-3 (110 mg, purity: 95%, yield: 85%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.06 – 3.95 (m, 2H), 2.78 (t, J = 13.5 Hz, 1H), 2.43 (t, J = 11.3 Hz, 1H), 2.27 – 2.17 (m, 2H), 1.99 (dd, J = 9.6, 3.3 Hz,1H), 1.92 – 1.83 (m, 2H), 1.78 – 1.61 (m, 4H), 1.53 (s, 3H), 1.50 – 1.35 (m, 8H), 1.30 (s, 6H), 1.26 (dd, J = 6.8, 4.5 Hz, 2H), 1.21 (s, 6H), 1.13 – 0.99 (m,5H), 0.92 (d, J = 6.4 Hz, 3H), 0.66 (s, 3H).

Step 4: Potassium tert-butoxide (106 mg, 1.95 mmol, 1.0 eq) was dissolved in dimethylformamide (3 mL) at room temperature, and p-toluenesulfonylmethyl isonitrile (79 mg, 0.38 mmol, 1.5 eq) was added at room temperature. After stirring at room temperature for 5 minutes, methanol (8.1 mg, 0.25 mmol, 1 eq), stirred at room temperature for 10 minutes, and then (3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR,12bR)-8-[(2R)-6-hydroxy-6-methylhept-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxolanecyclopentane-11-one 160-3 (120 mg, 0.253 mmol, 1.0 eq), stirred at room temperature for 12 hours, and monitored by TLC (petroleum ether: ethyl acetate = 3:1). After the reaction was completed, the mixture was quenched with water (30 mL), extracted with ethyl acetate (20 mL×2), the organic phase was washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 15:1) to obtain a white solid (3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12aR, 12bR)-8-[(2R)-6-hydroxy-6-methylhept-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexadecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxolanecyclopentane-11-carbonitrile 160-4 (30 mg, purity: 90%, yield: 25%). Compound 160-4 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.05 (dt, J = 8.4, 5.1 Hz, 2H), 2.93 (dd, J = 6.6, 4.4 Hz, 1H), 2.00 – 1.95 (m, 2H), 1.82 – 1.60 (m, 10H), 1.50 (s, 3H), 1.38 (ddd, J = 15.5, 11.4, 5.4 Hz, 10H), 1.30 (s, 3H), 1.25 (s, 5H), 1.22 (s, 6H), 1.05 (s, 3H), 0.93 (t, J = 6.0 Hz, 3H), 0.75 – 0.62 (m, 3H).

Step 5: (3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-8-[(2R)-6-hydroxy-6-methylhept-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxolanecyclopentane-11-carbonitrile 160-4 (30 mg, 0.06 mmol, 1 eq) was dissolved in tetrahydrofuran (3 mL) and 3 M hydrochloric acid (1 ml) at room temperature. ), then stirred at room temperature for 30 min, the reaction was monitored by TLC (petroleum ether: ethyl acetate = 1:1), after the reaction was completed, it was diluted with water (10 mL), extracted with ethyl acetate (10 mL×2), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain white solid 25-hydroxy-4β-hydroxy-3β-hydroxy-5α-cholesten-7-carbonitrile 160-5 (15 mg, purity: 80 %, yield: 50%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.76 (s, 1H), 3.69 – 3.61 (m, 1H), 2.93 (s, 1H), 2.27 – 2.18 (m, 1H), 2.12 – 1.96 (m, 4H), 1.89 (d, J = 9.6 Hz, 2H), 1.73(dd, J = 21.6, 11.8 Hz, 6H), 1.61 (dd, J = 11.3, 6.6 Hz, 6H), 1.46 (s, 2H), 1.37 (s, 3H), 1.28 (s, 2H), 1.25 (s, 3H), 1.22 (s, 3H), 1.04 (s, 3H), 0.92 (d, J =6.5 Hz, 3H), 0.66 (s, 3H).

Step 6: At room temperature, 25-hydroxy-4β-hydroxy-3β-hydroxy-5α-cholesten-7-carbonitrile 160-6 (10 mg, 0.022 mmol, 1.0 eq) was dissolved in dichloromethane (2 mL), and triethylamine (7 mg, 0.07 mmol, 3.0 eq), 4-dimethylaminopyridine (2.2 mg, 0.018 mmol, 0.8 eq) and benzoyl chloride (5 mg, 0.034 mmol, 1.5 eq) were added at room temperature. The mixture was stirred at room temperature for 1 hour and monitored by TLC (petroleum ether: ethyl acetate = 1:1). After the reaction was completed, the mixture was quenched with water (10 mL), extracted with ethyl acetate (10 mL×2), and the organic phase was saturated with brine (20 mL), dried over anhydrous sodium sulfate, concentrated the organic phase, purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) and chiral separation (instrument: Waters Acquity UPCC, chromatography column: Daicel CHIRALPAK IB 4.6*250mm, 5um, mobile phase: CO2/MeOH (0.1% DEA) = 60/40, flow rate: 1.5 ml/min, column temperature: 37 degree) to give white solid benzoic acid-(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-4-cyano-6-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 160-6 (8 mg, purity: 95%, yield: 80%, retention time: 1.595 min). ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.04 (d, J = 7.3 Hz, 2H), 7.57 (d, J = 7.4 Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 5.11 – 4.94 (m, 1H), 4.02 (s, 1H), 2.94 (s,1H), 2.24 – 2.09 (m, 2H), 1.99 (d, J = 12.5 Hz, 2H), 1.87 – 1.79 (m, 3H), 1.70 (d, J = 14.1 Hz, 3H), 1.38 (dd, J = 18.1, 12.4 Hz, 7H), 1.26 (d, J = 2.3Hz, 6H), 1.22 (s, 6H), 1.10 (d, J = 9.7 Hz, 4H), 0.91 (dd, J = 16.7, 6.4 Hz, 4H), 0.67 (s, 3H).

Step 7: At room temperature, white solid benzoic acid-(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-4-cyano-6-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl ester 160-6 (20 mg, 0.045 mmol, 1 eq) was dissolved in tetrahydrofuran (0.5 mL) and methanol (0.5 mL), and lithium hydroxide monohydrate (11 mg, 0.25 mmol, 10.0 eq) and water (0.2 mL) were added at room temperature, followed by stirring at room temperature for 30 min. TLC (petroleum ether: ethyl acetate = 10:1) to monitor the reaction. After the reaction was completed, it was diluted with water (10 mL), extracted with ethyl acetate (10 mL×2), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain white solid 25-hydroxy-4β-hydroxy-3β-hydroxy-5α-cholesten-7-carbonitrile 160 (12 mg, purity: 98.73 %, yield: 60%). Compound 160 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.76 (s, 1H), 3.66 (s, 1H), 2.93 (dd, J = 4.5, 2.3 Hz, 1H), 2.28 (dd, J = 37.9, 7.5 Hz, 2H), 2.16 – 2.04 (m, 2H), 2.04 – 1.94 (m, 3H), 1.89 (dd, J = 8.1, 4.5 Hz, 1H), 1.73 (dd, J = 8.7, 4.9 Hz, 3H), 1.66 – 1.58 (m, 4H), 1.49 – 1.40 (m, 6H), 1.33 (s, 4H), 1.22 (s, 6H), 1.09 (dd, J =12.7, 5.1 Hz, 2H), 1.04 (s, 3H), 0.92 (d, J = 6.5 Hz, 3H), 0.89 (d, J = 6.7 Hz, 2H), 0.66 (s, 3H). LC-MS: [MH]+ =445.36. Example 162 Preparation of Compound 162 4β- Hydroxy -3β- Hydroxy -24-[ Hydroxy (2- methoxyphenyl ) methyl ]-5α- cholane -7- carbonitrile

Step 1: Dissolve potassium tert-butoxide (19 mg, 0.169 mmol, 1.0 eq) in dimethylformamide (1 mL) at room temperature, add p-toluenesulfonylmethyl isonitrile (13 mg, 0.067 mmol, 1.5 eq) at room temperature, then stir at room temperature for 5 minutes and add methanol (1.44 mg, 0.045 mmol, 1 eq), stirred at room temperature for 10 minutes, and then (3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a, 10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta-11-one 106-4 (30 mg, 0.045 mmol, 1.0 eq), stirred at room temperature for 12 hours, monitored by TLC (petroleum ether: ethyl acetate = 3:1), quenched with water (30 mL) after the reaction, extracted with ethyl acetate (20 mL × 2), and the organic phase was saturated with brine (30 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 15: 1) to obtain a white solid (3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12aR, 12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b, 11,12,12a,12b-Hexadecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopentane-11-carbonitrile 162-1 (8 mg, purity: 90%, yield: 26%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.45 (d,J = 7.3Hz, 1H), 7.20 – 7.16 (m, 2H), 6.94 (t,J = 7.4Hz, 1H), 6.81 (d,J = 8.2Hz, 1H), 5.06 (s, 1H), 4.07 – 4.01(m, 3H), 3.81 (s, 3H), 2.92 (s, 1H), 2.34 (s, 1H), 2.25 – 2.18 (m, 1H), 1.99 (dd,J = 17.7, 8.8Hz, 4H), 1.89 – 1.82 (m, 3H), 1.74 – 1.67 (m, 5H), 1.63 – 1.58(m, 4H), 1.50 (s, 5H), 1.42 (d,J = 3.2Hz, 4H), 1.33 (s, 4H), 1.20 (d,J = 10.3Hz, 3H), 1.04 (s, 4H), 0.88 (s, 11H), 0.65 (d,J = 4.8Hz, 3H), 0.07 - 0.01(m, 4H), -0.14 (s, 2H).

Step 2: (3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopentane-11-carbonitrile 162-1 (20 mg, 0.03 mmol, 1 eq) was dissolved in tetrahydrofuran (3 mL) and 3M hydrochloric acid (1 mL), then stirred at room temperature for 30 min, the reaction was monitored by TLC (petroleum ether: ethyl acetate = 1:1), after the reaction was completed, it was diluted with water (10 mL), extracted with ethyl acetate (10 mL×2), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain white solid 4β-hydroxy-3β-hydroxy-24-[hydroxy(2-methoxyphenyl)methyl]-5α-cholane-7-carbonitrile 162 (12 mg, purity: 80 %, yield: 77.67%). Compound 162 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.32 – 7.27 (m, 1H), 7.23 (dd, J = 9.5, 1.8 Hz, 1H), 6.98 – 6.85 (m, 2H), 4.90 – 4.80 (m, 1H), 3.86 (s, 3H), 3.75 (s, 1H),3.67 – 3.60 (m, 1H), 2.92 (s, 1H), 2.35 – 2.15 (m, 1H), 2.11 – 1.90 (m, 5H), 1.77 – 1.65 (m, 7H), 1.61 – 1.57 (m, 1H), 1.50 – 1.44 (m, 3H), 1.37 (dd, J =11.6, 6.8 Hz, 3H), 1.33 (d, J = 4.8 Hz, 2H), 1.22 – 1.08 (m, 4H), 1.03 (s, 3H), 0.92 – 0.87 (m, 3H), 0.82 (dd, J = 18.0, 11.9 Hz, 1H), 0.65 (d, J = 2.3 Hz,3H). ¹³ C NMR (101 MHz, CDCl ₃ ) LC-MS: [MH] ^- =522.55. Example 170 & 180 & 181 : Compound 170 7-( Difluoromethyl )-24-[ hydroxy (2- methoxyphenyl ) methyl ]-5α -cholane- 3β,4β- diol compound 180 or 181 7-( Difluoromethyl )-24-[(S) -hydroxy (2- methoxyphenyl ) methyl ]-5α- cholane- 3β,4β- diol compound 181 or 180 Preparation of 7-( Difluoromethyl )-24-[(R) -hydroxy (2- methoxyphenyl ) methyl ]-5α- cholane- 3β,4β- diol

Step 1: (3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR, 12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a, 10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopentane-11-carbaldehyde 119-1 (90 mg, 0.132 mmol) was placed in a single-necked bottle, replaced with nitrogen, and diethylaminosulfur trifluoride (0.8 mL) was added. The mixture was stirred at room temperature for 2 hours. The reaction solution was dripped dropwise into stirred ice water, and then quenched by adding saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. The crude product was initially purified by flash chromatography (petroleum ether/ethyl acetate = 0-5%) and then separated by SFC (instrument: Waters Acquity, chromatography column: Daicel CHIRALPAK IF_3, 3.0*150mm, 3um mobile phase: A/B: CO2/MeOH (0.1% DEA) = 80/20, flow rate: 2.0 ml/min, column temperature: 37 ^o C, retention time: 1.010 min) to obtain (9R)-9-[(3aS,5aR,5bS,7aR, 8R,10aS,10bS,12aR,12bR)-11-(difluoromethyl)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladecane 170-1 (45 mg, 0.064 mmol, 48.43%) was obtained as a white solid. ¹ H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 7.6 Hz, 1H), 7.17 (dd, J = 7.7, 1.4 Hz, 1H), 6.95 (d, J = 7.4 Hz, 1H), 6.81 (d, J = 7.7 Hz, 1H), 6.03 (t, J = 56.2 Hz, 1H), 5.07 (d, J = 7.4 Hz, 1H), 4.05 – 3.95 (m, 2H), 3.81 (s, 3H), 2.16 – 2.05 (m, 1H), 1.93 (dd, J = 20.5, 13.0 Hz, 2H), 1.90 – 1.74 (m, 5H), 1.73 – 1.63 (m, 3H), 1.60 (dd, J = 9.7, 3.7 Hz, 3H), 1.50 (s, 3H), 1.49 – 1.32 (m, 5H), 1.30 (s, 3H), 1.29 – 1.11 (m, 8H), 1.08 19 F NMR (377 MHz, CDCl3) δ -116.07 ^, -116.08, -116.82, -116.83, -117.26, -117.27, -118.00, -118.02.

Step 2: (9R)-9-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-11-(difluoromethyl)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladecane 170-1 (40 mg, 0.057 mmol) was dissolved in tetrahydrofuran (3 mL), hydrochloric acid (0.5 mL, 2.000 mmol) was added, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction solution, extracted with ethyl acetate, and the organic phase was washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and rotary dried. The crude product was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2/1) to obtain 7-(difluoromethyl)-24-[hydroxy(2-methoxyphenyl)methyl]-5α-cholane-3β,4β-diol 170 (20 mg, 0.020 mmol, 35.23%) as a white solid. Compound 170 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.31 – 7.28 (m, 1H), 7.25 – 7.21 (m, 1H), 6.97 (dd, J = 15.8, 8.3 Hz, 1H), 6.88 (d, J = 8.2 Hz, 1H), 6.02 (td, J = 56.3, 2.9 Hz, 1H), 4.85 (dt, J = 9.2, 5.8 Hz, 1H), 3.86 (s, 3H), 3.75 (s, 1H), 3.63 – 3.52 (m, 1H), 2.07 (d, J = 31.9 Hz, 1H), 1.95 (d, J = 12.9 Hz, 1H), 1.87 (dd, J = 13.4, 5.5 Hz, 2H), 1.83 – 1.76 (m, 3H), 1.76 – 1.67 (m, 7H), 1.47 – 1.36 (m, 6H), 1.24 – 1.17 (m, 2H), 1.10 (d, J = 11.7 Hz, 4H), 1.06 (s, 3H), 1.01 (d, J = 3.9 Hz, 1H), 0.90 (dd, J = 6.4, 4.1 Hz, 3H), 0.64 (d, J = 2.4 Hz, 3H). ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -115.97, -116.72, -117.32, -118.07. LC-MS: MH] ^- = 547.45.

Step 3: 7-(Difluoromethyl)-24-[hydroxy(2-methoxyphenyl)methyl]-5α-cholane-3β,4β-diol (17 mg, 0.026 mmol) was chirally separated by SFC (instrument: Waters Acquity UPCC, chromatography column: Daicel CHIRALPAK IG_3, 3.0*150mm, 3um, mobile phase: A/B: CO2/MeOH(0.1%DEA)= 50/50, flow rate: 1.5 ml/min, Column Temp: 37 ^o C) to obtain 180 (2 mg, 0.004 mmol, 14.21%, retention time: 4.579 min) as a white solid and 181 (3 mg, 0.005 mmol, 21.32%, retention time: 5.925 min) is a white solid. 180: ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.30 (d, J = 7.2 Hz, 1H), 7.23 (d, J = 7.9 Hz, 1H), 6.96 (t, J = 7.4 Hz, 1H), 6.88 (d, J = 8.2 Hz, 1H), 6.02 (s, 1H), 4.86 (s, 1H), 3.86 (s, 3H), 3.74 (s, 1H), 3.56 (s, 1H), 2.50 (s, 1H), 2.01 – 1.94 (m, 2H), 1.86 (dd, J = 21.2, 8.3 Hz, 4H), 1.80 – 1.64 (m, 7H), 19 ^F NMR (376 MHz, CDCl ₃ ) δ -115.96, -116.71, -117.32, -118.07. LC-MS: [MH] ^- = 547.55. 181: ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.29 (d, J = 7.5 Hz, 1H), 7.23 (d, J = 7.9 Hz, 1H), 6.95 (t, J = 7.4 Hz, 1H), 6.88 (d, J = 8.2 Hz, 1H), 6.02 (d, J = 2.9 Hz, 1H), 4.84 (t, J = 6.7 Hz, 1H), 3.86 (s, 3H), 3.74 (s, 1H), 3.63 – 3.51 (m, 1H), 2.03 – 1.92 (m, 2H), 1.90 – 1.78 (m, 4H), 1.76 – 1.69 (m, 5H), 1.62 (dd, J = 16.6, 12.2 Hz, 5H), 1.47 – 1.37 (m, 4H), 1.31 – 1.24 (m, 4H), 1.10 (dd, J = 9.2, 3.6 Hz, 3H), 1.06 (s, 3H), 0.90 (d, J = 6.4 Hz, 3H), 0.64 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -115.96, -116.71, -117.32, -118.07. LC-MS (ESI) [MH] ^- = 547.55. Example 173 : Preparation of Compound 173 24-[(2- fluoro -6- methoxyphenyl )( hydroxy ) methyl ]-4β -hydroxy -3β- hydroxy - 5α- cholane -7- carbonitrile

Step 1: Dissolve (5R)-5-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a, 8,9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]hexan-1-ol III-1 (1 g, 2.322 mmol, 1 eq) in dichloromethane (15 mL) at room temperature, then add imidazole (0.47 g, 6.966 mmol, 1 eq) under stirring at room temperature. mmol, 3eq) and chlorodimethyl(2-methylprop-2-yl)silane (0.52 g, 3.483mmol, 1.5 eq) were added, and the reaction was monitored by TLC (petroleum ether:ethyl acetate = 5:1). After the reaction was completed, the mixture was diluted with water (100 mL), extracted with ethyl acetate (100 mL×2), and the organic phase was saturated with brine (20 mL) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 2:1) to obtain a white solid (9R)-9-[(3aS,5aR,5bS,7aR,8R,10aS,10bS,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-2,2,3,3-tetramethyl-4-oxa-3-siladecane 173-3 (1.1 g, purity: 90 %, yield: 87%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.80 (d, J = 2.6 Hz, 1H), 4.41 (d, J = 5.8 Hz, 1H), 4.10 (dd, J = 13.8, 6.2 Hz, 1H), 3.59 (t, J = 6.5 Hz, 2H), 2.16 – 1.98 (m, 2H), 1.88 – 1.79 (m, 1H), 1.75 – 1.69 (m, 1H), 1.66 – 1.54 (m, 6H), 1.53 (s, 3H), 1.51 – 1.33 (m, 11H), 1.25 (s, 2H), 1.20 – 1.00 (m, 10H), 0.91 (d, J = 6.9 Hz, 4H), 0.89 (s, 9H), 0.86 (t, J = 3.3 Hz, 2H), 0.69 (s, 3H), 0.07 – 0.03 (m, 6H).

Step 2: (9R)-9-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8, 9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-2,2,3,3-tetramethyl-4-oxa-3-siladecane 173-3 (1.2 g, 2.616 mmol, 1 eq) was dissolved in acetone (10 mL). Cobalt acetate (50 mg, 0.262 mmol, 1 eq) was added to the solution. 0.1eq), N-hydroxyphenylenediamine (90 mg, 0.523 mmol, 0.2 eq), tert-butyl peroxide (94 mg, 10.46 mmol, 4 eq), stirred at room temperature for 20 hours. After the reaction was completed, 30 mL of water was added and extracted with ethyl acetate (30 mL*3). The obtained organic phase was dried over anhydrous sodium sulfate and then rotary dried to obtain a crude product. The crude product was purified by silica gel column (petroleum ether/ethyl acetate = 10/1) to obtain (3aS,5aR,5bS,7aR,8R,10aS,10bS)-2,2,5a,7a-tetramethyl 8-[(9R)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-11-one 173 -4 (0.6 g, yield: 49%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.92 (s, 1H), 4.52 (d, J = 6.4 Hz, 1H), 4.33 (dd, J = 11.3, 5.6 Hz, 1H), 3.60 (t, J = 6.5 Hz, 2H), 2.36 (s, 2H), 2.04 (s, 1H), 1.91 – 1.78 (m, 2H), 1.65 – 1.54 (m, 9H), 1.45 – 1.32 (m, 13H), 1.27 (ddd, J = 10.0, 8.5, 5.9 Hz, 4H), 1.05 (s, 5H), 0.94 – 0.88 (m, 13H), 0.70 (s, 3H), 0.07 – 0.03 (m, 6H).

Step 3: Dissolve compound (3aS,5aR,5bS,7aR,8R,10aS, 10bS,12bR)-2,2,5a,7a-tetramethyl-8-[(9R)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-11-one 174-4 (0.6 g, 1.07 mmol, 1 eq) in ethyl acetate (15 mL), then add palladium on carbon (10%) (300 mg) to the solution. The mixture was stirred at room temperature for 12 hours. After the reaction was complete, the mixture was filtered and the organic solvent was dried by rotary evaporation to obtain the product (3aS,5aR,5bS,7aR,8R,10aS,10bS,12bR)-2,2,5a,7a-tetramethyl-8-[(9R)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-4,5,5a,5b,6,7, 7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta-11-one 173-5 ( 400 mg, 0.713 mmol, yield: 66%) as a white solid. ¹ H NMR (400 MHz, cdcl ₃ ) δ 3.96 (d,J = 3.5Hz, 2H), 3.57 (t,J = 6.6Hz, 2H), 2.75 (s, 1H), 2.41 (s, 1H), 2.17 (dd,J = 12.8, 2.8Hz, 2H), 2.00 –1.93 (m, 1H), 1.85 (ddd,J = 13.6, 6.6, 3.1Hz, 2H), 1.71 (ddd,J = 18.7, 11.5, 3.6Hz, 2H), 1.64 – 1.59 (m, 2H), 1.52 – 1.36 (m, 11H), 1.28 (s,6H), 1.24 – 1.14 (m, 4H), 1.08 – 0.99 (m, 4H), 0.88 (d,J = 6.6Hz, 13H), 0.64 (s, 3H), 0.03 (s, 6H).

Step 4: Compound (3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-2,2,5a,7a-tetramethyl-8-[(9R)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-4,5,5a,5b,6,7,7a,8,9,10,10a,10b, 11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta-11-one 173-5 (50 mg, 0.089 mmol, 1 eq) was dissolved in tetrahydrofuran (0.5 mL). Then tetrabutylammonium fluoride (1M) (0.89ml) was added thereto and stirred at room temperature for 12 hours. After the reaction was completed, 30mL of water was added and extracted with ethyl acetate (30mL*3). The obtained organic phase was dried over anhydrous sodium sulfate and then rotary dried to obtain a crude product. The crude product was purified by silica gel column (petroleum ether/ethyl acetate = 4/1) and then rotary dried to obtain the product (3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR,12bR)-8-[(2R)-6-hydroxyhexan-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10, 10a,10b,11,12,12a,12b-Hexadecahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopenta[11 -one 173-6 ( 35 mg, 0.078 mmol, yield: 87%) was obtained as a white solid. ¹ HNMR(400MHz, CDCl ₃ ) δ 4.09 – 3.93 (m, 2H), 3.64 (t,J = 6.6Hz, 2H), 2.77 (t,J = 13.6Hz, 1H), 2.43 (t,J = 11.3Hz, 1H), 2.20 (dt,J = 12.8,6.4Hz, 2H), 1.99 (d,J = 12.9Hz, 1H), 1.88 (ddd,J = 13.7, 6.8, 3.3Hz, 2H), 1.74 (dd,J = 13.3, 3.4Hz, 2H), 1.68 – 1.59 (m, 5H), 1.50 – 1.36 (m,8H), 1.30 (s, 6H), 1.22 (dd,J = 16.6, 10.8Hz, 3H), 1.14 – 1.03 (m, 5H), 0.93 – 0.90 (m, 4H), 0.66 (s, 3H).

Step 5: Dissolve potassium tert-butoxide (47.10 mg, 0.420 mmol, 3.75 eq) in dimethylformamide (1 mL) at room temperature, add p-toluenesulfonylmethyl isonitrile (33 mg, 0.168 mmol, 1.5 eq) at room temperature, then stir at room temperature for 5 minutes and then add methanol (3.5 mg, 0.67 mmol, 1 eq), stir at room temperature for 10 minutes and then add (3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12aR, 12bR)-8-[(2R)-6-hydroxyhexan-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxolanecyclopentane-11-one 173-6 (50 mg, 0.112 mmol, 1.0 eq) was stirred at room temperature for 12 hours. The reaction was monitored by TLC (petroleum ether:ethyl acetate = 3:1). After the reaction was completed, the mixture was quenched with water (30 mL), extracted with ethyl acetate (20 mL×2), and the organic phase was saturated with brine (30 mL) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 15:1) to obtain a white solid (3aS, 5aR, 5bS, 7aR, 8R, 10aS, 10bS, 12aR, 12bR)-8-[(2R)-6-hydroxyhexan-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b, 6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopentane-11-carbonitrile 173 -7 (25 mg, purity: 90%, yield: 49%). ¹ HNMR (400MHz, CDCl ₃ ) δ 4.09 – 4.01 (m, 2H), 3.70 – 3.59 (m, 2H), 2.92 (s, 1H), 2.03 – 1.95 (m, 2H), 1.81 – 1.66 (m, 5H), 1.60 – 1.52 (m, 4H), 1.43 –1.38 (m, 5H), 1.30 (s, 4H), 1.25 (s, 8H), 1.21 – 1.14 (m, 2H), 1.05 (s, 3H), 1.02 – 0.96 (m, 1H), 0.94 – 0.89 (m, 3H), 0.66 (d,J = 10.9Hz, 3H).

Step 6: The reactant (3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-8-[(2R)-6-hydroxyhexan-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxolanecyclopentane-11-carbonitrile 173-7 (60 mg, 0.131 mmol) and Dess-Martin oxide (166.80 mg, 0.393 mmol) were dissolved in dichloromethane (5 mL), replace the reaction system with nitrogen atmosphere, and stir at 25℃ for 2 h. Monitor the reaction by TLC, and a new spot appears at Rf=0.55, then stop the reaction. Add saturated sodium sulfite to quench (15 mL), add ethyl acetate to extract (20 mL), and rotate and dry the organic phase to obtain a crude product. The crude product was passed through a column with DCM:MeOH = 95:5 to 94:6 to give a white solid (3aS,5aR,5bS,7aR,8R,10aS,10bS, 12aR,12bR)-8-[(2R)-5-formylpentan-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxadiazol-11-carbonitrile 173-8 (40 mg, purity: 100%, yield: 66.96%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.76 (s, 1H), 4.03 (d, J = 4.0 Hz, 2H), 2.92 (d, J = 2.3 Hz, 1H), 2.39 (s, 2H), 1.97 (dd, J = 13.7, 4.1 Hz, 2H), 1.81 (d, J = 6.9 Hz, 3H), 1.74 – 1.65 (m, 5H), 1.41 (dd, J = 10.8, 5.3 Hz, 4H), 1.31 – 1.21 (m, 10H), 1.15 – 1.08 (m, 2H), 1.05 (s, 3H), 0.93 (d, J = 6.5 Hz, 3H), 0.67 (s, 3H).

Step 7: Dissolve the raw material 2-bromo-1-fluoro-3-methoxybenzene (47 mg, 0.2 mmol, 3.5 eq ) in anhydrous tetrahydrofuran (3 mL), cool the system to -78 ^o C, add n-butyl lithium (0.08 mL, 0.2 mmol, 3.0 eq ), and stir at the same temperature for 30 min. Compound (3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR, 12bR)-8-[(2R)-5-methylpentan-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopentane-11-carbonitrile 173-8 (30 mg, 0.066 mmol, 1.0 eq) was dissolved in tetrahydrofuran (2 mL) and added to the above reaction solution. The reaction system was stirred at -78 ^° C for 30 min. min. The reaction progress was monitored by TLC plate (petroleum ether: ethyl acetate = 5:1), and the raw material was completely consumed. 2. mL of water was added to the reaction system, extracted with ethyl acetate (30 mL × 3), and the combined organic phases were washed with saturated sodium chloride (30 The reaction mixture was washed with 4% paraformaldehyde and 1% paraformaldehyde (2% paraformaldehyde). The organic phases were combined, dried and concentrated to give colorless oily (3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR,12bR)-8-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopentane-11-carbonitrile 173-9 ( 11 mg, purity: 90%, yield: 28%). ¹ HNMR(400MHz, CDCl ₃ ) δ 7.17 (dd,J = 14.9, 8.3Hz, 1H), 6.74 – 6.63 (m, 2H), 5.01 (t,J = 7.0Hz, 1H), 4.03 (d,J = 3.7Hz, 2H), 3.92 – 3.84(m, 3H), 2.92 (s, 1H), 2.33 – 2.17 (m, 2H), 1.96 (dd,J = 13.0, 3.3Hz, 2H), 1.87 (dd,J = 12.8, 6.7Hz, 3H), 1.74 – 1.65 (m, 5H), 1.59 – 1.52 (m, 3H),1.43 – 1.33 (m, 5H), 1.30 – 1.25 (m, 8H), 1.17 (dd,J = 13.6, 9.7Hz, 3H), 1.05 (s, 3H), 0.88 (dd,J = 6.0, 2.4Hz, 3H), 0.68 – 0.63 (m, 3H).

Step 8: (3aS,5aR,5bS,7aR,8R,10aS,10bS, 12aR,12bR)-8-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b, 11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxolanecyclopentane-11-carbonitrile 173-9 (30 mg, 0.052 mmol, 1 eq) was dissolved in tetrahydrofuran (3 mL) and 3 M hydrochloric acid (1 ml) at room temperature. ), then stirred at room temperature for 30 min, the reaction was monitored by TLC (petroleum ether: ethyl acetate = 1:1), after the reaction was completed, it was diluted with water (10 mL), extracted with ethyl acetate (10 mL×2), the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain white solid 24-[(2-fluoro-6-methoxyphenyl)(hydroxy)methyl]-4β-hydroxy-3β-hydroxy-5α-cholane-7-carbonitrile 173 (23 mg, purity: 96%, yield: 75%). Compound 173 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.17 (d, J = 6.6 Hz, 1H), 6.74 – 6.65 (m, 2H), 5.01 (t, J = 7.5 Hz, 1H), 3.88 (s, 3H), 3.76 (s, 1H), 3.67 – 3.62 (m, 1H), 2.93 (s, 1H), 2.47 – 2.13 (m, 2H), 2.08 (dd, J = 13.5, 4.5 Hz, 1H), 1.97 – 1.84 (m, 4H), 1.75 – 1.65 (m, 8H), 1.47 (d, J = 13.0 Hz, 3H), 1.36 (dd, J = 13.8, 7.1 Hz, 5H), 1.16 (d, J = 4.4 Hz, 3H), 1.04 (s, 3H), 0.92 (s, 1H), 0.88 (dd, J = 6.5, 2.3 Hz, 3H), 0.64 (d, J = 4.0 Hz, 3H). ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -117.15, -117.21. LCMS (ESI) [M+Na] ⁺ =564.3. Example 178 : Compound 178 Preparation of (1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-1-[(2R)-6- hydroxy -6-(2- methoxyphenyl ) hexan -2- yl ]-9a,11a - dimethyl -1,2,3,3a,3b,5,5a,6,7,8,9,9a,9b,10,11,11a -hexadecano [ cyclopenta [1,2-a] phenanthrene -4,1'- cyclopropane ]-6,7- diol

Step ¹ : 24-[Hydroxy(2-methoxyphenyl)methyl]-7-methylidene-5α-cholane-3β,4β-diol 106 (30 mg, 0.059 mmol, 1.0 eq) and diiodomethane (314.64 mg, 1.175 mmol, 20.0 eq) were added to a three-necked flask containing dichloromethane (5 mL) at 0 ° C. Then, diethylzinc (1M n-hexane solution) (1.175 mL, 1.175 mmol, 20.0 eq) was slowly added dropwise to the system under nitrogen protection. The mixture was stirred at 0 ^° C for 1 hour. LCMS detection showed that the reaction of the raw material was complete, and the reaction was stopped. The reaction solution was quenched with dilute hydrochloric acid (10 mL, 1 mol/L), and the aqueous layer was extracted with ethyl acetate (3×10 mL). The ethyl acetate layers were combined and washed with saturated brine (3×10 mL). The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and concentrated to obtain a crude product. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 65: 35) to give a white solid product (1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-hydroxy-6-(2-methoxyphenyl)hexan-2-yl]-9a, 11a-dimethyl-1,2,3,3a, 3b, 5,5a, 6,7,8,9,9a,9b, 10,11,11a-hexahydrospiro[cyclopenta[1,2-a]phenanthrene-4,1'-cyclopropane]-6,7-diol 515 (15.53 mg, purity 92.86%, yield 46.79%). Compound 178 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.31 – 7.27 (m, 1H), 7.25 – 7.21 (m, 1H), 6.95 (t, J = 7.4 Hz, 1H), 6.88 (d, J = 8.2 Hz, 1H), 4.84 (dt, J = 9.5, 5.8 Hz, 1H), 3.85 (s, 3H), 3.65 (s, 1H), 3.57 (dt, J = 11.4, 4.3 Hz, 1H), 2.35 (t, J = 12.7 Hz, 1H), 2.04 – 1.82 (m, 5H), 1.82 – 1.60 (m, 7H), 1.38 – 1.23 (m,8H), 1.12 – 1.06 (m, 4H), 1.05 – 0.96 (m, 3H), 0.93 – 0.76 (m, 7H), 0.63 (d, J = 2.5 Hz, 3H), 0.50 (d, J = 8.5 Hz, 1H), 0.31 (dd, J = 13.4, 2.5 Hz,1H), -0.01 (d, J = 4.3 Hz, 2H). LC-MS: [MH] ^- = 523.60. Example 179 : Compound 179 Preparation of [(1R,3aS,3bS,5aS,7S,9aR,9bS,11aR)-7- hydroxy -1-[(2R)-6- hydroxy -6- methylhept -2- yl ]-9a,11a -dimethylhexahydro -1H - cyclopenta [1,2-a] phenanthrene -6- yl ] acetic acid

Step 1: In a 50 mL round-bottom flask, methoxymethylidene triphenylphosphine (1814 mg, 5.43 mmol) and (1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-6-oxoylidene hexadecahydro-1H-cyclopenta[1,2-i]phenanthrene-7-yl acetate 123-5 (250 mg, 0.54 mmol) were mixed at room temperature and the mixture was stirred at 160 °C for 10 hours. The reaction was monitored by TLC (petroleum ether/ethyl acetate = 10/1). After the reaction was completed, water (30 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (20 mL×3). The extracted organic solution was washed with saturated brine (30 mL), dried with anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified and separated by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 10/1) to give white solid [(1R,3aS,3bS,5aR,6E,7S,9aR,9bS,11aR)-7-acetyloxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-ylidene]acetate 179-2 (105 mg, purity: 85%, yield: 31.83%). ¹ H NMR (400 MHz, CDCl3) δ 5.80 – 5.65 (m, 1H), 5.36 (dd, J=49.8, 6.4, 1H), 3.67 (s, 3H), 2.07 (s, 3H), 2.01 – 1.38 (m, 29H), 1.21 (s, 6H), 0.92(d, J=6.3, 3H), 0.88 (s, 3H), 0.66 (s, 3H). ¹³ C NMR (101 MHz, CDCl3) δ 172.06, 171.34, 129.58, 128.88, 74.32, 71.11, 56.29, 56.17, 54.28, 53.69, 51.88, 47.30, 46.24, 44.42, 42.48, 39.82,39.57, 38.58, 36.76, 36.42, 35.73, 35.05, 33.62, 31.10, 29.36, 29.20, 28.21, 26.92, 24.43, 24.13, 20.99, 20.76, 20.62, 18.66, 13.56, 12.73, 12.00.

Step 2: In a 50 mL round-bottom flask, [(1R,3aS,3bS,5aR,6E,7S,9aR,9bS,11aR)-7-acetyloxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-ylidene]acetate 179-2 (85 mg, 0.16 mmol) was dissolved in methanol (5 mL), 10% Pd/C (52 mg, 0.049 mmol) was added at room temperature, and the mixture was stirred in a hydrogen atmosphere at room temperature for 16 hours. The reaction was monitored by TLC (ethyl acetate/petroleum ether = 10:1). After the reaction was completed, the reaction solution was diluted with ethyl acetate (10 mL), filtered through diatomaceous earth, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain white solid [(1R, 3aS, 3bS, 5aS, 7S, 9aR, 9bS, 11aR)-7-acetyloxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]acetate methyl ester 179-3 (69 mg, purity: 70%, yield: 56.60%). ¹ H NMR (400 MHz, CDCl3) δ 4.70 (t, J=10.4, 1H), 3.66 (s, 3H), 2.04 (s, 3H), 2.01 – 1.61 (m, 15H), 1.50 – 1.35(m, 17H), 1.21(s, 6H), 0.91(d, J=6.5, 3H), 0.85 (s, 3H), 0.64 (s, 3H).

Step 3: In a 50 mL round-bottom flask at room temperature, [(1R,3aS,3bS,5aS,7S,9aR,9bS,11aR)-7-acetyloxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]acetate 179-3 (49 mg, 0.094 mmol) was dissolved in tetrahydrofuran (1 mL) and methanol (1 mL). Lithium hydroxide monohydrate (40 mg, 0.95 mmol) and water (0.5 mL) were added at room temperature. The mixture was stirred at room temperature for 16 hours. The reaction was monitored by TLC (dichloromethane: methanol = 10:1). After the reaction was completed, 1M The pH was adjusted to 4-5 with hydrochloric acid, diluted with water (10 mL), extracted with ethyl acetate (10 mL×3), the organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (dichloromethane:methanol=10:1) to obtain white solid [(1R,3aS,3bS,5aS,7S,9aR,9bS,11aR)-7-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethylhexahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]acetic acid 179 (10 mg, purity: 97.18%, yield: 22.24%). Compound 179 : ¹ H NMR (400 MHz, DMSO-d6) δ 4.03 (s, 1H), 2.96 – 2.79 (m, 1H), 2.72 – 2.61 (m, 2H), 2.24 – 2.09 (m, 1H), 2.05 – 1.39 (m, 17H), 1.20 – 1.07 (m, 7H), 1.05 (s, 6H), 1.01 – 0.92 (m, 5H), 0.88 (d, J =6.4, 3H), 0.73 (s, 3H), 0.62 (s, 3H). ¹ LC-MS; [MH] ^- =461.4. Example 185 : Compound 185 Preparation of [(1R,3aS,3bS,5aS,7S,9aS,9bS,11aR)-4,4-difluoro-1-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexyl-2-yl]-7-hydroxy-9a,11a-dimethylhexahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]acetonitrile

Step 1: Dissolve the reactant (5R)-5-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a, 5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]hexanoic acid methyl ester I-13 (2.3 g, 4.63 mmol, 1.0 eq) in tetrahydrofuran (20 mL), add dilute hydrochloric acid (1 mL, 3 mol/L), the reaction system was stirred at room temperature for 1 hour. The reaction progress was monitored by TLC plate (petroleum ether: ethyl acetate = 10:1). Water (30 mL) was added to the reaction system, and the aqueous layer was extracted with ethyl acetate (2×40 mL). The EA layers were combined and washed with saturated brine (50 mL). The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and concentrated to obtain a crude product. The crude product was purified by column chromatography (40 g, 0-20% ethyl acetate/petroleum ether, 40 mL/min) and (dichloromethane:methanol=20:1) to give white solid (5R)-5-[(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-4,4-difluoro-6,7-dihydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 185-1 (1.9 g, purity 90%, yield 80.9%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.74 (s, 1H), 3.67 (s, 3H), 3.64 – 3.57 (m, 1H), 2.31 – 2.23 (m, 2H), 1.97 (d, J = 12.9 Hz, 1H), 1.90 – 1.77 (m, 5H), 1.75 – 1.63 (m, 5H), 1.49 – 1.37 (m, 6H), 1.35 – 1.28 (m, 2H), 1.11 (dd, J = 10.7, 6.0 Hz, 3H), 1.06 (s, 3H), 0.98 (dd, J = 17.7, 7.3 Hz, 2H), 0.93 (d, J = 6.6 Hz, 3H), 0.66 (s, 3H).

Step 2: At room temperature, (5R)-5-[(1R,3aS,3bS,5aR,6R, 7S,9aR,9bS,11aR)-4,4-difluoro-6,7-dihydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 185-1 (1.8 g, 3.94 mmol, 1 eq) was dissolved in dichloromethane (30 mL), cooled to 0 ^o C in an ice bath, and imidazole (0.80 g, 11.83 mmol, 3 eq) and TBSCl (1.19 g, 7.88 mmol, 2 eq) were added, and then stirred at room temperature for 3 hours. The reaction was detected by TLC plate (petroleum ether:ethyl acetate = 20:1, phosphomolybdic acid baking plate). Dilute with dichloromethane (30 mL), wash with water (40 mL) and saturated brine (40 mL), dry over anhydrous sodium sulfate, filter, and concentrate to obtain a crude product. After separation by chromatography column (20 g, 0-2% ethyl acetate/petroleum ether, 40 mL/min), a white solid product (5R)-5-[(1R,3aS,3bS,5aR,6R,7S,9aR, 9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-6-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 185-2 (2.1 g, purity: 90%, yield 84.0%) was obtained. ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.67 (s, 3H), 3.61 – 3.55 (m, 2H), 2.35 – 2.13 (m, 3H), 1.97 (d, J = 12.7 Hz, 1H), 1.89 – 1.65 (m, 7H), 1.54 – 1.17 (m, 12H), 1.11 (dd, J = 13.0, 4.3 Hz, 2H), 1.07 (s, 3H), 1.00 – 0.95 (m, 1H), 0.93 (d, J = 6.5 Hz, 3H), 0.89 (s, 9H), 0.66 (s, 3H), 0.07 (d, J = 3.4 Hz, 6H).

Step 3: Compound (5R)-5-[(1R,3aS,3bS,5aR,6R, 7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-6-hydroxy-9a,11a-dimethylhexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 185-2 (2.1 g, 3.679 mmol) was dissolved in dichloromethane (40 mL), cooled in an ice bath, and Dess-Martin reagent (4.68 g, 11.04 mmol) was added, followed by stirring at room temperature for 3 hours. The reaction was detected to be complete by TLC plate (petroleum ether:ethyl acetate = 4:1). Add 20% sodium thiosulfate solution and sodium bicarbonate solution to the reaction solution, stir for 10 min, and extract with ethyl acetate (50 mL x 2). Combine the organic phases and wash with saturated brine (80 mL), dry over anhydrous sodium sulfate, filter, and concentrate to obtain a crude product. After separation by chromatography column (20 g, 0-3% ethyl acetate/petroleum ether, 40 mL/min), white solid (5R)-5-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-9a,11a-dimethyl-6-oxyylidenehexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 185-3 (1.8 g, 77.42%) was obtained. ¹ H NMR (400 MHz, CDCl ₃ ) δ 4.19 (dd, J = 11.5, 7.8 Hz, 1H), 3.67 (s, 3H), 2.40 (d, J = 10.2 Hz, 1H), 2.34 – 2.17 (m, 3H), 2.02 (dd, J = 18.0, 10.8 Hz, 2H), 1.85 (ddd, J = 23.5, 12.5, 3.9 Hz, 5H), 1.66 (dd, J = 28.5, 21.8 Hz, 3H), 1.50 – 1.38 (m, 4H), 1.37 – 1.23 (m, 5H), 1.19 – 1.05 (m, 3H), 0.93 (d, J = 6.5 Hz, 3H), 0.89 (d, J = 2.9 Hz, 9H), 0.77 (s, 3H), 0.66 (s, 3H), 0.13 (d, J = 3.4 Hz, 3H), 0.02 (s, 3H).

Step 4: Dissolve methyltriphenylphosphonium bromide (5.21 g, 14.591 mmol) in tetrahydrofuran (30 mL) at room temperature, slowly add potassium tert-butoxide solution (1M in THF, 14.6 mL, 14.6 mmol) dropwise, and stir for 2 hours. Then, a solution of the raw material (5R)-5-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-9a,11a-dimethyl-6-oxyylidene hexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 185-3 (1.66 g, 2.918 mmol) in tetrahydrofuran (10 mL) was added dropwise. The mixture was stirred at room temperature for 2 hours. The reaction was complete by TLC plate (petroleum ether:ethyl acetate = 20:1). The reaction solution was quenched by adding water (40 mL) and extracted with ethyl acetate (40 mLx2). The organic phases were combined and washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The product was separated by chromatography column (25 g, 0-10% ethyl acetate/petroleum ether, 30 mL/min) to obtain (5R)-5-[(1R, 3aS, 3bS, 5aR, 7S, 9aR, 9bS, 11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 185-4 (400 mg, 12.09%). ¹ H NMR (400 MHz, CDCl3) δ 4.93 (s, 1H), 4.72 (s, 1H), 3.87 (d, J = 10.1 Hz, 1H), 3.66 (s, 3H), 2.28 (dd, J = 8.7, 6.7 Hz, 6H), 1.96 (d, J = 12.6 Hz, 2H), 1.83 (d, J = 7.3Hz, 4H), 1.73 (s, 5H), 1.45 – 1.40 (m, 5H), 1.29 (d, J = 3.6 Hz, 3H), 1.12 – 1.05 (m, 4H), 0.95 (s, 9H), 0.92 (s, 3H), 0.66 (s, 3H), 0.07 (s, 3H), 0.04 (s, 3H).

Step 5: At room temperature, (5R)-5-[(1R,3aS,3bS,5aR, 7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester 185-4 (380 mg, 12 mL) was dissolved in tetrahydrofuran (12 mL), cooled to 0 °C in an ice bath, and then LiAlH ₄ (76.30 mg, 2.011 mmol) was added in portions. The above mixture was heated at 0 °C. ℃ for 1 hour. The reaction was complete by TLC plate (petroleum ether: ethyl acetate = 50:1). Sodium sulfate decahydrate was added to the reaction solution, stirred for 20 minutes, filtered through diatomaceous earth, washed with ethyl acetate (30 mL), and the filtrate was concentrated to obtain a crude product. Separated by chromatography column (12 g, 0-15% ethyl acetate/petroleum ether, 30 mL/min) to give white solid (5R)-5-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-9a,11a-dimethyl-6-methylidenehexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexan-1-ol 185-5 (260 mg, 64.78%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 5.05 (d, J = 98.8 Hz, 1H), 4.63 (d, J = 73.9 Hz, 1H), 3.99 – 3.84 (m, 1H), 3.64 (t, J = 6.0 Hz, 2H), 2.46 – 1.67 (m, 9H), 1.62 – 1.39 (m, 13H), 1.29 (s, 3H), 1.08 (ddd, J = 18.5, 18.1, 11.7 Hz, 6H), 0.96 – 0.91 (m, 12H), 0.85 (dd, J = 14.0, 6.6 Hz, 1H), 0.69 – 0.62 (m, 3H), 0.04 (dd, J = 14.3, 7.9 Hz, 6H).

Step 6: Compound (5R)-5-[(1R,3aS,3bS,5aR, 7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexan-1-ol 185-5 (260 mg, 0.482 mmol) was dissolved in dichloromethane (8 mL), cooled in an ice bath, and Dess-Martin periodinane (613.92 mg, 1.447 mmol) was added, followed by stirring at room temperature for 3 hours. The reaction was complete by TLC plate (petroleum ether:ethyl acetate = 20:1). Add 20% sodium thiosulfate solution and sodium bicarbonate solution to the reaction solution, stir for 10 minutes, and extract with dichloromethane (20 mLx2). Combine the organic phases and wash with saturated brine (20 mL), dry over anhydrous sodium sulfate, filter, and concentrate to obtain a crude product. After separation by chromatography column (4 g, 0-3% ethyl acetate/petroleum ether, 20 mL/min), a white solid (5R)-5-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-9a,11a-dimethyl-6-methylidenehexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanal 185-6 (165 mg, 0.277 mmol, 57.33%) was obtained. ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.76 (d, J = 1.8 Hz, 1H), 5.05 (d, J = 99.0 Hz, 1H), 4.63 (d, J = 74.6 Hz, 1H), 3.99 – 3.83 (m, 1H), 2.40 (dd, J = 13.4, 6.8 Hz, 3H), 1.97 (t, J = 9.8 Hz, 2H), 1.80 (dd, J = 40.9, 8.7 Hz, 6H), 1.51 – 1.38 (m, 6H), 1.33 (s, 3H), 1.28 (s, 3H), 1.12 (dd, J = 27.6, 22.7 Hz, 5H), 0.97 – 0.90 (m, 9H), 0.69 – 0.63 (m, 3H), 0.09 – 0.03 (m, 6H).

Step 7: Dissolve 2-bromo-1-fluoro-3-methoxybenzene (173.77 mg, 0.848 mmol) in anhydrous tetrahydrofuran (4 mL), cool the system to -78 ^° C, add n-butyl lithium (0.291 mL, 0.85 mmol), and stir at the same temperature for 30 min. Compound (5R)-5-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanal 185-6 (130 mg, 0.242 mmol) in tetrahydrofuran (3 mL) was added to the above reaction solution, and the reaction system was stirred at -78 ^° C for 30 min. The reaction progress was monitored by TLC plate (petroleum ether:ethyl acetate = 30:1). 20 mL of water was added to the reaction system, and ethyl acetate (20 mL×2) was used for extraction. The combined organic phases were washed with saturated sodium chloride (30 mL), and the combined organic phases were dried and concentrated to obtain a crude product. The crude product was purified by column chromatography (4 g, 0-5% ethyl acetate/petroleum ether, 20 mL/min) to obtain a white solid (5R)-5-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-1-(2-fluoro-6-methoxyphenyl)hexan-1-ol 185-7 (90 mg, 50.45%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.17 (dd, J = 15.2, 7.7 Hz, 1H), 6.72 – 6.65 (m, 2H), 5.02 (dd, J = 52.5, 46.2 Hz, 2H), 4.63 (d, J = 73.6 Hz, 1H), 3.93 (d, J = 12.9 Hz, 1H), 3.87 (d, J = 10.1 Hz, 3H), 2.37 – 2.15 (m, 2H), 1.98 (d, J = 11.7 Hz, 3H), 1.79 (dd, J = 36.8, 8.9 Hz, 7H), 1.48 – 1.33 (m, 8H), 1.18 – 1.00 (m, 6H), 0.97 – 0.91 (m, 12H), 0.88 (dd, J = 8.9, 4.7 Hz, 3H), 0.65 (d, J = 4.7 Hz, 3H), 0.08 – 0.01 (m, 6H).

Step 8: (5R)-5-[(1R,3aS,3bS,5aR,7S,9aR, 9bS,11aR)-7-{[dimethyl(2-methylprop-2-yl)silyl]oxy}-4,4-difluoro-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-1-(2-fluoro-6-methoxyphenyl)hexan-1-ol 185-7 (85 mg, 0.128 mmol) was dissolved in anhydrous tetrahydrofuran (1 mL) at room temperature, and a solution of tetrabutylammonium fluoride in tetrahydrofuran (1 M, 2 mL, 2.0 mmol) was added, followed by stirring at room temperature for 1 hour. The reaction solution was slowly added to 20 mL of water, extracted with ethyl acetate (20 mL x 2), the organic phases were combined and washed with water (30 mL) and saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The product was separated by a chromatography column (4 g, 0-10% ethyl acetate/petroleum ether, 20 mL/min) to obtain compound (1R, 3aS, 3bS, 5aR, 7S, 9aR, 9bS, 11aR)-4,4-difluoro-1-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-9a, 11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 185-8 (22 mg, 28.1%)). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.17 (td, J = 8.4, 6.6 Hz, 1H), 6.69 (dt, J = 8.6, 4.5 Hz, 2H), 5.13 (s, 1H), 5.00 (dd, J = 10.2, 4.2 Hz, 1H), 4.60 (s, 1H), 4.01 (dd, J = 11.5, 5.4 Hz, 1H), 3.88 (s, 3H), 2.24 (dd, J = 21.9, 13.7 Hz, 1H), 1.99 (t, J = 9.6 Hz, 3H), 1.91 – 1.75 (m, 6H), 1.72 – 1.59 (m, 3H), 1.47 – 1.33 (m, 7H), 1.22 – 1.02 (m, 6H), 0.90 (dd, J = 6.5, 4.2 Hz, 3H), 0.72 (s, 3H), 0.66 (d, J = 4.6 Hz, 3H).

Step 9: Dissolve ((1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-4,4-difluoro-1-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-9a,11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol (30 mg, 0.055 mmol) in tetrahydrofuran (2 mL), cool to 0 ^o C in an ice bath, slowly add borane dimethyl sulfide complex (2M in THF) (0.205 mL), then warm to room temperature and stir for 3 hours. Cool to 0 ^o C in an ice bath, slowly add sodium hydroxide solution (0.082 mL) and H ₂ O ₂ (92.94 mg, 0.820 mmol), then warm to room temperature and stir for 15 hours. The reaction was detected to be complete by TLC plate (petroleum ether: ethyl acetate = 5:1, phosphomolybdic acid baking plate). The reaction solution was quenched with sodium sulfite solution, 10 mL of water was added, and ethyl acetate was extracted (10 mLx2). The organic phase was combined and washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. Separated by chromatography column (4 g, 0-40% ethyl acetate/petroleum ether, 20 mL/min) to obtain compound (1R,3aS,3bS,5aS,7S,9aS,9bS,11aR)-4,4-difluoro-1-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-6-(hydroxymethyl)-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 185-9 (23 mg, 66.80%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.17 (dd, J = 14.9, 8.4 Hz, 1H), 6.72 – 6.66 (m, 2H), 5.01 (s, 1H), 4.25 (t, J = 10.5 Hz, 1H), 3.88 (s, 3H), 3.82 (dd, J = 11.2, 4.7 Hz, 1H), 3.63 (dd, J = 10.4, 4.1 Hz, 1H), 2.34 (t, J = 33.1 Hz, 3H), 1.90 (dd, J = 52.8, 9.7 Hz, 4H), 1.71 (dd, J = 11.9, 8.0 Hz, 6H), 1.41 (dd, J = 22.3, 7.5 Hz, 7H), 1.18 – 0.94 (m, 7H), 0.89 (dd, J = 6.4, 3.8 Hz, 3H), 0.84 (s, 3H), 0.65 (d, J = 4.5 Hz, 3H).

Step 10: Dissolve (1R,3aS,3bS,5aS,7S,9aS, 9bS,11aR)-4,4-difluoro-1-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-6-(hydroxymethyl)-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 185-9 (22 mg, 0.039 mmol) in dichloromethane (2 mL) at room temperature, add 4-(dimethylamino)pyridine (4.74 mg, 0.039 mmol) and triethylamine (23.57 mg, 0.233 mmol), cool to 0 ^o C in an ice bath, and slowly add p-toluenesulfonyl chloride (14.80 mg, 0.078 mmol) in dichloromethane (1 mL). After 10 min, the temperature was raised to 50 ^° C and stirred for 16 hours. The reaction was detected by TLC plate (petroleum ether: ethyl acetate = 2:1, molybdenum phosphate baking plate), showing that new spots were generated and some raw materials were not consumed. The reaction solution was diluted with DCM (10 mL), washed with water (10 mL) and saturated salt water (10 mL) in sequence, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The residue was separated by chromatography column (4 g, 0-40% ethyl acetate/petroleum ether, 20 mL/min) to obtain white solid 4-methylbenzenesulfonic acid [(1R,3aS,3bS,5aS,7S,9aS,9bS,11aR)-4,4-difluoro-1-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-7-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methyl ester 185-10 (15 mg, 48.25%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.81 (d, J = 8.3 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.17 (dd, J = 14.9, 8.3 Hz, 1H), 6.69 (dt, J = 8.6, 4.5 Hz, 2H), 5.01 (s, 1H), 4.29 (dd, J = 9.7, 4.2 Hz, 1H), 4.14 (dd, J = 18.0, 8.4 Hz, 1H), 3.88 (s, 3H), 3.72 (dd, J = 11.5, 5.8 Hz, 1H), 2.45 (s, 3H), 2.27 (dd, J = 28.0, 13.0 Hz, 2H), 2.01 – 1.73 (m, 6H), 1.71 – 1.57 (m, 4H), 1.48 – 1.30 (m, 9H), 1.15 – 0.95 (m, 6H), 0.89 (dd, J = 6.3, 3.5 Hz, 3H), 0.82 (s, 3H), 0.63 (d, J = 4.5 Hz, 3H).

Step 11: 4-Methylbenzenesulfonic acid [(1R,3aS,3bS,5aS, 7S,9aS,9bS,11aR)-4,4-difluoro-1-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-7-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]methyl ester 185-10 (15 mg, 0.021 mmol) was dissolved in N,N-dimethylformamide (1 mL) at room temperature, and then sodium cyanide (15.29 mg, 0.312 mmol) was added and heated in an oil bath at 100 °C for 16 hours. The reaction was detected by TLC plate (petroleum ether:ethyl acetate = 2:1). The reaction solution was added to 10 mL of water and extracted with ethyl acetate (10 mL x 2). The organic phases were combined and washed with water (20 mL x 3) and saturated brine (20 mL). The product was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The product was separated by chromatography column (4 g, 0-20% ethyl acetate/petroleum ether, 20 mL/min) to obtain a white solid product [(1R,3aS,3bS,5aS,7S,9aS,9bS,11aR)-4,4-difluoro-1-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-7-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-yl]acetonitrile 185 (2.46 mg, purity 92.8%, yield 19.10%). Compound 185 : ¹ HNMR (400 MHz, CDCl3) δ 7.17 (dd, J = 15.0, 8.4 Hz, 1H), 6.74 – 6.65 (m, 2H), 5.01 (s, 1H), 3.88 (s, 3H), 3.78 (d, J = 10.7 Hz, 1H), 3.20 (s, 1H), 2.76(t, J = 6.5 Hz, 1H), 2.33 (dt, J = 15.0, 6.9 Hz, 3H), 2.04 – 1.91 (m, 2H), 1.86 (dd, J = 20.2, 9.7 Hz, 4H), 1.79 – 1.65 (m, 4H), 1.48 – 1.40 (m, 3H), 1.40 –1.34 (m, 4H), 1.16 – 1.03 (m, 6H), 0.88 (dt,J = 15.3, 6.6Hz, 8H), 0.64 (t,J = 5.8Hz, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ -88.80 (d, J = 238.7 Hz, 1F), -110.59 (d, J = 238.6 Hz, 1F), -117.23 (d, J = 20.6 Hz, 1F). LC-MS: [M+H] + = 574.50. Example 186 Compound 186 Preparation of [(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-1-[(2R)-6-(2,4 -difluoro -6- methoxyphenyl )-6- hydroxyhexan -2 - yl ]-6,7 -dihydroxy -9a, 11a-dimethylhexahydro -1H- cyclopenta [1,2-a] phenanthrene -4- yl ] acetonitrile

Step 1: Referring to the synthesis of compound 159-2 in Example 159 , [(3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR,12bR)-8-[(2R)-6-(2,4-difluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-11-yl]acetonitrile 186-6 (18 mg, 0.025 mmol, 23.42%) was a white solid. ¹ H NMR (400 MHz, CDCl3) δ 6.51 – 6.38 (m, 2H), 4.99 – 4.90 (m, 1H), 4.02 – 3.98 (m, 2H), 3.86 (s, 3H), 2.58 – 2.45 (m, 2H), 1.99 (d, J = 11.0 Hz, 2H), 1.85 – 1.77 (m, J = 12.1 Hz, 6H), 1.75 – 1.65 (m, 8H), 1.51 (s, 6H), 1.42 – 1.34 (m, 6H), 1.30 (s, 3H), 1.09 – 1.06 (m, 3H), 1.04 (s, 3H), 0.95 – 0.90 (m, 3H), 0.70 (d, J = 3.9 Hz, 3H).

Step 2: Dissolve [(3aS,5aR,5bS,7aR,8R,10aS,10bS, 12aR,12bR)-8-[(2R)-6-(2,4-difluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a, 10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[11-yl]acetonitrile 186-6 (18 mg, 0.029 mmol) in tetrahydrofuran (3 mL), add hydrochloric acid (1 mL, 3.000 mmol), the mixture was stirred at room temperature for 1 hour. Water was added to the reaction solution, extracted with ethyl acetate, the organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and rotary dried. The crude product was purified by flash chromatography (petroleum ether/ethyl acetate = 50%) to obtain [(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-1-[(2R)-6-(2,4-difluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-6,7-dihydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-4-yl]acetonitrile 186 (2.5 mg, 0.004 mmol, 13.96%) as a white solid. Compound 186 : ¹ H NMR (400 MHz, CDCl3) δ 6.45 (d, J = 10.0 Hz, 2H), 4.94 (s, 1H), 3.86 (s, 3H), 3.74 (s, 1H), 3.57 (s, 1H), 2.54 (d, J = 4.1 Hz, 2H), 1.98 (d, J = 11.7 Hz,2H), 1.86 (s, 2H), 1.76 (d, J = 10.7 Hz, 4H), 1.56 (s, 5H), 1.33 (s, 3H), 1.28 (s, 2H), 1.25 (s, 3H), 1.12 (d, J = 13.9 Hz, 3H), 1.03 (s, 3H), 0.94 (d, J = 6.8 Hz, 2H), 0.89 (t, J = 6.2 Hz, 3H), 0.71 – 0.67 (m, 4H). LC-MS: [M+H] ⁺ = 538.45. Example 187 : Preparation of Compound 187 [(1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-(4- fluoro -2- methoxyphenyl )-6- hydroxyhexan -2- yl ]-6,7 -dihydroxy -9a, 11a -dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -4- yl ] acetonitrile

The synthesis of Reference Example 186 can obtain [(1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-(4-fluoro-2-methoxyphenyl)-6-hydroxyhexan-2-yl]-6,7-dihydroxy-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-4-yl]acetonitrile 187 (40 mg, purity: 96%, yield: 61.44%). Compound 187 : ¹ H NMR (400 MHz, CDCl3) δ 7.26 – 7.21 (m, 1H), 6.63 (ddd, J=13.2, 9.6, 2.0, 2H), 4.83 (dd, J=13.3, 7.3, 1H), 3.83 (s, 3H), 3.74 (s, 1H), 3.56 (dd, J=6.6, 3.7, 1H), 2.54 (d, J=4.2, 2H), 2.01 – 1.65 (m, 14H), 1.59 – 1.31 (m, 13H), 1.03 (s, 3H), 0.89 (dd, J=6.3, 3.2, 3H), 0.69 (d, J=1.4, 3H). ¹⁹ F NMR (377 MHz, CDCl3) δ = -112.96 (d, J=22.4, 1F). LC-MS: [M+Na] ⁺ =578.3. Examples 196 & 208 & 209 Compound 196 [(1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-(6- fluoro -2- methoxyphenyl )-6- hydroxyhexan -2- yl ]-6,7 -dihydroxy -9a, 11a- dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -4- yl ] acetonitrile Compound 208 or 209 [(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-1-[(2R,6S)-6-(6- fluoro -2- methoxyphenyl )-6- hydroxyhexan -2 - yl ]-6,7 -dihydroxy -9a,11a -dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -4- yl ] acetonitrile compound 209 or 208 Preparation of [(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-1-[(2R,6R)-6-(2- fluoro -6- methoxyphenyl )-6- hydroxyhexan - 2- yl ]-6,7 -dihydroxy -9a,11a -dimethylhexahydro -1H- cyclopenta [1,2-a] phenanthrene -4- yl ] acetonitrile

The synthesis of Reference Example 186 can obtain white solid [(1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-(6-fluoro-2-methoxyphenyl)-6-hydroxyhexan-2-yl]-6,7-dihydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-4-yl]acetonitrile 196 (62 mg). After chiral separation (instrument: Waters Acquity UPC, chromatography column: REGIS CHIRAL (S,S)-Whelk O1, 150 mm×4.6 mm, 3.5 um, mobile phase: CO2/MeOH (0.1% DEA) = 50/50, flow rate: 1.5 ml/min, column temperature: 37 °C), white solid 208 (20 mg, purity: 100%, yield: 21.44%, retention time: 3.323 min) and 209 (25 mg, purity: 100%, yield: 26.80%, retention time: 3.625 min) were obtained. 196 : ¹ H NMR (400 MHz, CDCl3) δ = 7.17 (dd, J=15.0, 8.2, 1H), 6.75 – 6.63 (m, 2H), 5.05 – 4.96 (m, 1H), 3.88 (s, 3H), 3.74 (s, 1H), 3.63 – 3.49 (m, 1H), 2.54 (s, 2H), 2.07 – 1.62 (m, 11H), 1.62 – 1.28 (m, 12H), 1.17 – 1.05 (m, 4H), 1.03 (s, 3H), 0.89 (dd, J=7.8, 4.7, 3H), 0.68 (d, J=4.9, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -117.25 (d, J=40.4, 1F). LC-MS: [M+Na] ⁺ =578.3. 208: ¹ H NMR (400 MHz, CDCl3) δ = 7.17 (td, J=8.3, 6.6, 1H), 6.74 – 6.65 (m, 2H), 5.01 (dd, J=8.2, 6.1, 1H), 3.88 (s, 3H), 3.74 (s, 1H), 3.56 (dd, J=6.8,3.7, 1H), 2.54 (d, J=4.5, 2H), 2.01 – 1.67 (m, 11H), 1.62 – 1.29 (m, 12H), 1.20 – 1.05 (m, 4H), 1.03 (s, 3H), 0.90 (d, J=6.5, 3H), 0.69 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -117.31 (s, 1F). LC-MS: [M+Na] ⁺ =578.4. 209: ¹ H NMR (400 MHz, CDCl3) δ = 7.17 (dd, J=14.9, 8.3, 1H), 6.74 – 6.65 (m, 2H), 5.00 (t, J=7.2, 1H), 3.88 (s, 3H), 3.74 (s, 1H), 3.61 – 3.51 (m, 1H), : 2.53 (d, J=2.1, 2H), 2.01 – 1.65 (m, 11H), 1.62 – 1.27 (m, 12H), 1.16 – 1.05 (m, 4H), 1.03 (s, 3H), 0.88 (d, J=6.5, 3H), 0.68 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -117.20 (s, 1F). LC-MS: [M+Na] ⁺ =578.3. Example 219 : Compound 219 Preparation of (1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-6- amino -4,4 -difluoro -1-[(2R)-6-(4- fluoro -2- methoxyphenyl )-6- hydroxyhexan - 2- yl ]-9a, 11a-dimethylhexadecahydro -1H- cyclopenta [1,2-a] phenanthrene -7- ol

Step 1: The reactant 1-bromo-4-fluoro-2-methoxybenzene (1.54 g, 7.500 mmol) was dissolved in tetrahydrofuran (5 mL). The reaction system was replaced with a nitrogen atmosphere. n-Butyl lithium, 2.5 M hexane solution (3.0 mL, 7.500 mmol) was added at -78°C and stirred for 0.5 h. Then, (5R)-5-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b, 6,7,7a,8,9,10,10a,10b,11,12,12a,12b-Hexadecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]hexanal I (1 g, 2.143 mmol). The reaction was monitored by TLC. A new spot appeared at Rf=0.55. The reaction was stopped. Saturated ammonium chloride (25 mL) was added to quench the reaction. Ethyl acetate (25 mL×3) was added to extract the reaction. The organic phase was dried by rotary drying to obtain a crude product. The crude product was passed through a column with DCM:MeOH = 95:5 to 94:6 to obtain a white solid (5R)-5-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]-1-(4-fluoro-2-methoxyphenyl)hexan-1-ol 219-1 (700 mg, 1.181 mmol, Purity: 100%, Yield: 55.11%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.23 (s, 1H), 6.62 (m, 3H), 4.84 (dd, J = 13.7, 7.5 Hz, 1H), 4.00 (d, J = 3.3 Hz, 2H), 3.83 (s, 3H), 1.82 (m, 22H), 1.51 (s, 4H), 1.30 (s, 4H), 1.07 (s, 6H), 0.90 (m, 3H), 0.67 (d, J = 1.2 Hz, 3H).

Step 2: Compound (5R)-5-[(3aS,5aR,5bS,7aR, 8R,10aS,10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]-1-(4-fluoro-2-methoxyphenyl)hexan-1-ol (500 mg, 0.84 mmol, 1.0 eq ) was dissolved in dichloromethane (20 mL), and acetic anhydride (0.238 mL, 2.53 mmol, 3.0 eq ), triethylamine (0.35 mL, 2.53 mmol, 3.0 eq ) and 4-dimethylaminopyridine (DMAP) (103 mg, 0.84 mmol, 1.0 eq ), stirred at room temperature for 3 hours, and the reaction was monitored by TLC (petroleum ether: ethyl acetate = 5:1). After the reaction was completed, the reaction solution was washed with sodium bicarbonate and saturated brine, the organic phase was dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 90:10) to obtain white solid acetic acid-(5R)-5-[(3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a, 10b,11,12, 12a,12b-Hexadecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]-1-(4-fluoro-2-methoxyphenyl)hexyl ester 219-2 (500 mg, purity: 90%, yield: 84.04%). ¹ H NMR (400 MHz, CDCl3) δ 7.23 (m, 1H), 6.60 (m, 2H), 6.09 (m, 1H), 4.01 (m, 2H), 3.84 (d, J = 12.7 Hz, 3H), 2.07 (d, J = 1.3 Hz, 3H), 1.96 (m, 3H), 1.74 (m,9H), 1.61 (d, J = 13.7 Hz, 2H), 1.51 (s, 4H), 1.30 (s, 3H), 1.07 (s, 3H), 0.96 (m, 2H), 0.87 (dd, J = 6.3, 4.4 Hz, 3H), 0.66 (d, J = 1.7 Hz, 3H). ¹⁹ F NMR (377 MHz, CDCl3) δ -89.00, -89.63, -111.37, -111.99, -112.47, -112.55.

Step 3: The compound was obtained as a white solid. Acetic acid-(5R)-5-[(3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b, 11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]-1-(4-fluoro-2-methoxyphenyl)hexyl ester (500 mg, 0.79 mmol) was dissolved in tetrahydrofuran (10 mL), and 3 N dilute hydrochloric acid (2 mL), stirred at room temperature for 3 hours, and the reaction was monitored by TLC (petroleum ether: ethyl acetate = 5:1). After the reaction was completed, the reaction solution was washed with sodium bicarbonate (10 mL) and saturated brine (10 mL). The organic phase was dried over anhydrous sodium sulfate and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 70:30) to obtain white solid acetate-(5R)-5-[(1R,3aS,3bS,5aR,6R, 7S,9aR,9bS,11aR)-4,4-difluoro-6,7-dihydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-1-(4-fluoro-2-methoxyphenyl)hexyl ester 219-3 (350 mg, purity: 90%. Yield: 67.24%). ¹ H NMR (400 MHz, CDCl3) δ 7.24 (m, 1H), 6.60 (m, 2H), 6.08 (s, 1H), 3.84 (d, J = 12.6 Hz, 3H), 3.74 (d, J = 4.1 Hz, 1H), 3.60 (d, J = 10.5 Hz, 1H), 2.07 (d, J =1.4 Hz, 3H), 1.96 (d, J = 12.1 Hz, 1H), 1.84 (ddd, J = 11.6, 7.4, 3.3 Hz, 5H), 1.70 (m, 4H), 1.57 (s, 7H), 1.36 (m, 6H), 1.05 (d, J = 5.4 Hz, 4H), 0.98 (d, J = 10.6Hz, 2H), 0.87 (dd, J = 6.4, 4.3 Hz, 3H), 0.65 (d, J = 1.8 Hz, 3H).

Step 4: Compound (5R)-5-[(1R,3aS,3bS,5aR, 6R,7S,9aR,9bS,11aR)-4,4-difluoro-6,7-dihydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-1-(4-fluoro-2-methoxyphenyl)hexyl acetate (300 mg, 0.50 mmol, 1.0 eq ) was dissolved in dichloromethane (20 mL). Under nitrogen protection, Desmartin oxidant (214 mg, 0.50 mmol, 1.0 eq ) was added in batches at room temperature. The reaction was kept warm for 2 hours and monitored by TLC (petroleum ether: ethyl acetate = 3:1). After the reaction was completed, the reaction solution was washed with dichloromethane (20 The mixture was diluted with saturated sodium thiosulfate (20 mL), washed with saturated brine (20 mL), the organic phase was dried over anhydrous sodium sulfate, and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 80:20) to obtain yellow solid acetate-(5R)-5-[(1R, 3aS, 3bS, 5aR, 7S, 9aR, 9bS, 11aR)-4,4-difluoro-7-hydroxy-9a, 11a-dimethyl-6-oxyylidene hexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-1-(4-fluoro-2-methoxyphenyl)hexyl ester 219-4 (200 mg, purity: 90%. Yield: 60.20%) . ¹ H NMR (400 MHz, CDCl3) δ 7.23 (m, 1H), 6.61 (ddd, J = 13.3, 9.6, 4.6 Hz, 2H), 6.09 (dd, J = 7.3, 4.4 Hz, 1H), 4.13 (m, 2H), 3.82 (s, 3H), 2.45 (m, 2H), 2.09(m, 4H), 2.00 (d, J = 12.6 Hz, 2H), 1.85 (m, 4H), 1.65 (m, 7H), 1.43 (s, 3H), 1.35 (m, 5H), 1.10 (m, 5H), 0.88 (dt, J = 8.3, 2.9 Hz, 4H), 0.77 (d, J = 7.0 Hz, 3H), 0.64 (dd, J = 14.8, 1.9 Hz, 3H).

Step 5: Dissolve the raw material (5R)-5-[(1R,3aS,3bS,5aR,7S, 9aR,9bS,11aR)-4,4-difluoro-7-hydroxy-9a,11a-dimethyl-6-oxyylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-1-(4-fluoro-2-methoxyphenyl)hexyl acetate (125 mg, 0.21 mmol, 1.0 eq ) and sodium acetate, anhydrous (103.79 mg, 1.27 mmol, 6.0 eq ) in ethanol (20 mL), and add hydroxylamine hydrochloride (88 mg, 1.27 mmol, 6.0 eq ). The reaction mixture was stirred at 90 ^° C for 5 hr under nitrogen atmosphere. LCMS showed that the starting material was almost consumed, the product could be detected, and the reaction was stopped. Water (10 mL) was added to the reaction system, and the mixture was extracted with ethyl acetate (10 mL x 2). The combined organic phases were washed with saturated brine (10 mL), then dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 60:40) to obtain a white solid acetate-(5R)-5-[(1R,3aS,3bS,5aR,6Z,7S, 9aR,9bS,11aR)-4,4-difluoro-7-hydroxy-6-(hydroxyamido)-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-1-(4-fluoro-2-methoxyphenyl)hexyl ester 219-5 (50 mg, purity: 90%, yield: 35.1%). LCMS (ESI) [M+H] ⁺ = 608.3.

Step 6: Dissolve the raw material (5R)-5-[(1R,3aS,3bS,5aR,6Z, 7S,9aR,9bS,11aR)-4,4-difluoro-7-hydroxy-6-(hydroxyamido)-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-1-(4-fluoro-2-methoxyphenyl)hexyl acetate (40 mg, 0.07 mmol, 1.0 eq ) in a mixed solvent of tetrahydrofuran (1 mL) and methanol (2 mL), and add lithium hydroxide (8 mg, 0.33 mmol, 5.0 eq). The reaction mixture was stirred at 40 ^° C for 5 hours. LCMS showed that the reaction was complete, and the reaction was stopped. Water (10 mL) was added to the reaction system, and the mixture was extracted with ethyl acetate (10 mL x 3). The combined organic phases were washed with saturated brine (10 mL), then dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 60:40) to obtain [(1R, 3aS, 3bS, 5aR, 7S, 9aR, 9bS, 11aR)-4,4-difluoro-1-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-7-hydroxy-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-ylidene]hydroxyamine 219-6 (30 mg, purity: 80%, yield: 64.46%). LCMS (ESI) [M+H] ⁺ = 566.2.

Step 7: Dissolve the raw material [(1R,3aS,3bS,5aR,7S,9aR,9bS, 11aR)-4,4-difluoro-1-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-7-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-6-ylidene]hydroxylamine (30 mg, 0.05 mmol, 1.0 eq ) in tetrahydrofuran (5 mL), and add lithium aluminum tetrahydrogen (20 mg, 0.53 mmol, 10.0 eq ). The reaction mixture was stirred at 80 ^° C for 5 hours under nitrogen atmosphere. LCMS showed that the reaction was completed and the reaction was stopped. Water (10 mL) was added to the reaction system, and the mixture was extracted with ethyl acetate (10 mL x 3). The combined organic phases were washed with saturated brine (10 mL), then dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (dichloromethane: methanol = 10: 1) to obtain a white solid (1R, 3aS, 3bS, 5aR, 7S, 9aR, 9bS, 11aR)-6-amino-4,4-difluoro-1-[(2R)-6-(2-fluoro-6-methoxyphenyl)-6-hydroxyhexan-2-yl]-9a, 11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 219 (9.63 mg, 0.015 mmol, purity: 86.2%, yield: 28.4%). Compound 219 : ¹ H NMR (400 MHz, DMSO) δ 7.37 (m, 1H), 6.81 (m, 1H), 6.72 (m, 1H), 4.92 (d, J = 4.8 Hz, 1H), 4.78 (m, 1H), 4.61 (s, 1H), 3.77 (m, 3H), 3.42 (d, J = 11.7 Hz, 1H), 2.89 (dd, J = 33.8, 30.5 Hz, 1H), 2.13 (ddd, J = 30.9, 14.1, 9.6 Hz, 1H), 1.91 (d, J = 10.7 Hz, 1H), 1.72 (dd, J = 30.6, 9.6 Hz, 6H), 1.55 (d, J = 13.1 Hz,2H), 1.37 (m, 14H), 1.05 (s, 2H), 1.03 (s, 3H), 0.95 (d, J = 13.4 Hz, 2H), 0.85 (d, J = 6.1 Hz, 3H), 0.62 (d, J = 2.2 Hz, 3H). ¹⁹ F NMR (377 MHz, DMSO) δ -86.55, -87.17, -108.55, -109.17, -114.37, -114.44. LC-MS: [M+H] ⁺ = 552.3. Example 300 : Compound 300 Preparation of 7-[fluoromethylidene]-24-[hydroxy(2-methoxyphenyl)methyl]-5α,8α-cholane-3β,4β-diol in," " indicates that the configuration is not clear, for example, express and/or .

Step 1: (3aS,5aR,5bS,7aR,8R,10aS,10bS,12aR, 12bR)-8-[(9R)-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladec-9-yl]-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10, 10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':7,8]phenanthro[1,2-d][1,3]dioxacyclopentane-11-carbaldehyde 170-1 (90 mg, 0.132 mmol) was placed in a single-necked bottle, replaced with nitrogen, and diethylaminosulfur trifluoride (0.8 mL) was added. The mixture was stirred at room temperature for 2 hours. The reaction solution was dripped dropwise into stirred ice water, and then quenched by adding saturated sodium bicarbonate aqueous solution. The mixture was extracted with ethyl acetate, and the organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. The crude product was initially purified by flash chromatography (petroleum ether/ethyl acetate = 0-5%) and then separated by SFC (Instrument: Waters Acquity, UPCC Column: Daicel CHIRALPAK IF_3, 3.0*150mm, 3um Mobile, Phase: A/B: CO2/MeOH(0.1%DEA)=80/20, Flow rate: 2.0 ml/min, Column Temp: 37 degree, Retention time: 1.300 min) to obtain (9R)-9-[(3aS,5aR,5bS,7aR,8R,10aS,10bS, 12aR,12bR)-11-fluoromethyl-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7, 7a,8,9,10,10a,10b,11,12,12a,12b-Hexadecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladecane 300-1 (40 mg, purity: 100%, yield: 44.36%) was obtained as a white solid. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.46 (d, J = 7.6 Hz, 1H), 7.18 (s, 1H), 6.95 (d, J = 7.4 Hz, 1H), 6.81 (d, J = 7.8 Hz, 1H), 6.57 – 6.27 (m, 1H), 5.06 (s, 1H), 4.08 (d, J = 3.6 Hz, 1H), 4.03 – 3.94 (m, 1H), 3.81 (s, 3H), 2.70 (dd, J = 13.1, 2.5 Hz, 1H), 2.14 – 2.05 (m, 1H), 2.03 – 1.89 (m, 2H), 1.87 – 1.76 (m, 3H), 1.72 – 1.53 (m, 6H), 1.52 (s, 3H), 1.50 – 1.33 (m, 7H), 1.32 (s, 3H), 1.26 (d, J = 5.1 Hz, 4H), 1.16 (s, 3H), 1.12 19 F NMR (377 MHz ^, 377 MHz) CDCl ₃ ) δ -135.27, -135.33, -143.94, -143.96.

Step 2: (9R)-9-[(3aS,5aR,5bS,7aR,8R,10aS, 10bS,12aR,12bR)-11-fluoromethylidene-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]-5-(2-methoxyphenyl)-2,2,3,3-tetramethyl-4-oxa-3-siladecane 300-1 (40 mg, 0.059 mmol) was dissolved in tetrahydrofuran (3 mL), hydrochloric acid (0.8 mL, 3.20 mmol) was added, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction solution, extracted with ethyl acetate, and the organic phase was washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and rotary dried. The crude product was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 2/1) to obtain 7-fluoromethylidene-24-[hydroxy(2-methoxyphenyl)methyl]-5α,8α-cholane-3β,4β-diol 300 (4 mg, purity: 99.68%, yield: 11.54%) as a white solid. Compound 300 : ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.30 (d, J = 7.5 Hz, 1H), 7.23 (d, J = 7.7 Hz, 1H), 6.96 (t, J = 7.5 Hz, 1H), 6.88 (d, J = 8.2 Hz, 1H), 6.43 (d, J = 88.6 Hz, 1H), 4.85 (dt, J = 9.5, 6.0 Hz, 1H), 3.86 (s, 3H), 3.83 (s, 1H), 3.61 – 3.50 (m, 1H), 2.67 – 2.55 (m, 1H), 2.02 (dd, J = 23.3, 11.1 Hz, 4H), 1.88 – 1.63 (m, 9H), 1.41 (d, J = 12.1 Hz, 5H), 1.30 – 1.22 (m, 3H), 1.13 (s, 3H), 1.11 – 1.03 (m, 4H), 0.91 (dd, J = 6.4, 3.9 Hz, 3H), 0.66 (d, J = 2.3 Hz, 3H). ¹⁹ F NMR (376 MHz, CDCl ₃ ) δ -144.07. LC-MS: [MH] ^- = 527.50. Example 376 Compound 376 Preparation of (1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-1-[(2R)-5- hydroxy -5- methylhexan -2- yl ]-9a,11a -dimethyl -1,2,3,3a,3b,5,5a,6,7,8,9,9a,9b,10,11,11a- hexahydrospiro [ cyclopenta [1,2-a] phenanthrene -4,1'- cyclopropane ]-7 -ol

In the first step , 6α-hydroxy-3α-hydroxy-5β-cholan-24-oic acid IV-1 (15 g, 38.2 mmol, 1.0 eq) was dissolved in MeOH (methanol) (200 mL). Sulfuric acid (5 mL, 93.8 mmol, 2.5 eq) was slowly added to the reaction system and the reaction mixture was stirred at 75 ^° C for 2 hours. After the reaction was complete as monitored by TLC (dichloromethane: methanol = 10:1), the temperature was lowered to room temperature, and the reaction solution was slowly added to saturated sodium bicarbonate (~200 mL). The reaction system was washed once with saturated sodium bicarbonate solution (~100 mL) and water (~100 mL), dried over anhydrous sodium sulfate, and concentrated to dryness to obtain a crude product of 6α-hydroxy-3α-hydroxycholan-24-oic acid methyl ester IV-2 (15 g, yield 86.90%), which was directly used for the next step.

Step 2: 6α-Hydroxy-3α-hydroxy-5β-cholan-24-oic acid methyl ester IV-2 (15.0 g, 36.9 mmol, 1.0 eq) was dissolved in pyridine (50 mL), p-toluenesulfonyl chloride (42.2 g, 221.3 mmol, 6 eq) was added at room temperature, stirred at room temperature overnight, and TLC (petroleum ether: ethyl acetate = 5:1) was used to detect the completion of the reaction. The reaction solution was poured into a 5% hydrochloric acid solution (100 mL) with crushed ice. After the solid precipitated, it was filtered, washed with water, and dried to obtain the crude product 4-methylbenzenesulfonic acid-(1R,3aS,3bS,5aR,5S, 7R,9aR,9bS,11aR)-1-[(2R)-5-methoxy-5-oxyylidenepentan-2-yl]-9a,11a-dimethyl-7-{[(4-methylphenyl)dioxyylidene-λ6-sulfenyl]oxy}hexahydro-1H-cyclopenta[1,2-a]phenanthrene-5-yl ester IV-3 (20 g, yield 70.20%).

Step 3 4-Methylbenzenesulfonic acid-(1R,3aS,3bS,5aR,5S, 7R,9aR,9bS,11aR)-1-[(2R)-5-methoxy-5-oxyylidenepentan-2-yl]-9a,11a-dimethyl-7-{[(4-methylphenyl)dioxyylidene-λ6-thio]oxy}hexahydro-1H-cyclopenta[1,2-a]phenanthrene-5-yl ester IV-3 (10 g, 69.9 mmol, 1.0 eq) was dissolved in water (20 mL) and N,N-dimethylformamide (200 mL), the system was heated to 110 ^o C, and refluxed for 4 hours. TLC (petroleum ether: ethyl acetate = 5:1) monitored the reaction. After the reaction was complete, the mixture was cooled to room temperature and a white solid precipitated. The reaction solution was poured into a 5% hydrochloric acid solution (500 mL) with crushed ice, washed with water (50 mL x 2), and dried to obtain an intermediate, which was then dissolved in a 4% KOH methanol solution (250 mL). The reaction mixture was stirred at room temperature for 3 hours. TLC (petroleum ether: ethyl acetate = 5:1) was used to monitor the reaction. After the reaction was complete, 5% hydrochloric acid was used to adjust the pH to neutral, the reaction solution was extracted with ethyl acetate (100 mL x 3), washed with saturated brine (100 mL x 3), dried over anhydrous sulfuric acid, and the organic phase was collected and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 30:1 to 10:1 to 5:1) to obtain white solid 3β-hydroxycholan-5(6)-ene-24-oic acid methyl ester IV-4 (30 g, yield 75.6%).

Compound IV-4 : 1H NMR (400 MHz, CDCl3) δ 5.37 – 5.33 (m, 1H), 3.66 (s, 3H), 2.34 (dt, J = 13.0, 4.0 Hz, 1H), 2.30 – 2.23 (m, 2H), 2.24 – 2.18 (m, 2H), 2.05 –1.93 (m, 3H), 1.82 (tdd, J = 10.1, 8.1, 4.9 Hz, 5H), 1.53 – 1.40 (m, 7H), 1.36 – 1.25 (m, 3H), 1.01 (s, 3H), 0.92 (t, J = 5.1 Hz, 5H), 0.68 (s, 4H).

Step 4: In a 1000 mL round-bottom flask at room temperature, IV-4 (35 g, 90.07 mmol) was dissolved in dichloromethane (500 mL), and imidazole (18.37 g, 270.21 mmol) and tert-butyldimethylsilyl chloride (37.13 g, 135.10 mmol) were added at room temperature. The mixture was stirred at room temperature for 4 hours and monitored by TLC (petroleum ether: ethyl acetate = 10:1). After the reaction was completed, the mixture was quenched with water (500 mL), extracted with ethyl acetate (400 mL×3), and the organic phase was saturated with brine (600 mL×400 mL). mL), dried over anhydrous sodium sulfate, the organic phase was concentrated, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 20: 1) to obtain white solid 3β-{[(2-methylpropan-2-yl)diphenylsilyl]oxy}cholan-6(5)-ene-24-oic acid methyl ester 376-1 (40 g, purity: 90 %, yield: 63.75 %). Compound 783-1 : 1H NMR (400 MHz, CDCl3) δ = 7.68 (dd, J=5.0, 3.5, 4H), 7.42 – 7.37 (m, 6H), 5.14 (d, J=5.0, 1H), 3.66 (s, 3H), 3.55 (td, J=10.8, 4.6, 1H), 2.43 – 2.10 (m, 5H), 2.03 – 1.29 (m, 20H), 1.07 (s, 9H), 0.99 (s, 3H), 0.92 (d, J=6.4, 3H), 0.66 (s, 3H).

Step 5: In a 1000 mL round-bottom flask at room temperature, 376-1 (30 g, 47.85 mmol) was dissolved in acetone (300 mL). N-hydroxyphthalide (3.12 g, 19.14 mmol), cobalt acetate (1.69 g, 9.57 mmol) and tert-butyl hydroperoxide (39.87 mL, 239.23 mmol) were added at room temperature. The mixture was stirred at 40 °C for 30 hours. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 10:1). After the reaction was completed, the reaction solution was diluted with dichloromethane (200 mL), filtered through diatomaceous earth, and washed with dichloromethane (300 mL). The filter cake was washed with 200 mL × 3 of 4-nitropropane-5-yl)diphenylsilyloxy}-7-oxyylidenecholan-5(6)-ene-24-oic acid methyl ester 376-2 (15 g, purity: 90%, yield: 44.02%). Compound 376-2 : ¹ H NMR (400 MHz, CDCl3) δ = 7.66 (dd, J=6.8, 1.1, 4H), 7.44 – 7.36 (m, 6H), 5.45 (d, J=1.4, 1H), 3.65 (s, 3H), 3.64 – 3.55 (m, 1H), 2.50 – 2.15 (m, 7H), 2.00 – 1.62 (m, 8H), 1.55 – 1.29 (m, 8H), 1.16 (s, 3H), 1.06 (s, 9H), 0.91 (d, J=6.4, 3H), 0.65 (s, 3H).

Step 6 In a 500 mL round-bottom flask, 376-2 (20 g, 31.20 mmol) was dissolved in 1 M tetrabutylammonium fluoride tetrahydrofuran solution (100 mL) and stirred at room temperature for 2 hours. The reaction was monitored by TLC (ethyl acetate/petroleum ether = 5:1). After the reaction was completed, water (200 mL) was added to the reaction solution, and the reaction solution was extracted with ethyl acetate (150 mL×3), dried over anhydrous sodium sulfate, concentrated the organic phase, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain a colorless oily substance 3β-hydroxy-7-oxyylidenecholan-6(5)-ene-24-oic acid methyl ester 376-3 (11.75 g, purity: 90%, yield: 84.19%).

Compound 376-3 : ¹ H NMR (400 MHz, CDCl3) δ = 5.69 (d, J=1.5, 1H), 3.71 – 3.63 (m, 4H), 2.54 – 2.19 (m, 6H), 2.06 – 1.75 (m, 6H), 1.67 – 1.21 (m, 11H), 1.19 (s, 3H), 0.93 (d, J=6.4, 3H), 0.68 (s, 3H).

Step 7: Methyltriphenylphosphonium bromide (854 mg, 2.4 mmol, 5 eq) was dissolved in tetrahydrofuran (10 mL) at room temperature. Potassium tert-butoxide (1.0 M IN THF) (2.4 mL, 2.4 mmol, 5 eq) was added under stirring. After stirring at room temperature for 20 min, 376-3 (200 mg, 0.48 mmol, 1 eq) was added. After one hour at room temperature, the reaction was monitored by TLC (petroleum ether:ethyl acetate = 2:1). 100 mL of water was added for dilution at room temperature, and the mixture was extracted with ethyl acetate (100 mL×2). The organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain white solid 3β-hydroxy-7-methylidene-5α-cholan-24-oic acid methyl ester 376-4 (180 mg, purity: 98.8%, yield: 91%). Compound 376-4 : ¹ H NMR (400 MHz, CDCl3) δ 5.01 – 4.85 (m, 1H), 3.71 – 3.62 (m, 4H), 2.33 – 2.21 (m, 2H), 2.00 – 1.83(m, 5H), 1.64 – 1.35 (m, 11H), 1.25 – 1.19(m, 2H), 1.08 – 1.00 (m, 4H), 0.93 – 0.89 (m, 6H), 0.78 (dd, J = 11.5,7.1 Hz, 1H), 0.64 (d, J = 7.5 Hz, 3H), 0.48 (t, J = 4.9 Hz, 1H), 0.11 (dd, J =8.5, 4.7 Hz, 1H).

Step 8 In a 1000 mL round-bottom flask, compound 376-4 (12 g, 18.72 mmol) was dissolved in methanol (200 mL) and ethyl acetate (200 mL), 10% Pd/C (4 g, 3.75 mmol) was added at room temperature, and the mixture was stirred in a hydrogen atmosphere at 40 °C for 3 hours. TLC (ethyl acetate/petroleum ether = 5:1) was used to detect the reaction, and a new compound was generated. After the reaction was completed, the reaction solution was diluted with ethyl acetate (200 mL), filtered through diatomaceous earth, and the filter cake was washed with ethyl acetate (200 mL×3). The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain a colorless oil compound 376-5 (7 g, yield: 52.34%). Compound 376-5 : 1HNMR (400MHz, CDCl3) δ = 3.59 (s, 3H), 3.58 – 3.49 (m, 1H), 2.33 – 2.23 (m, 3H), 2.19 – 2.10 (m, 2H), 1.99 – 1.66 (m, 8H), 1.58 – 1.19 (m,13H), 1.01 (s, 3H), 0.85 (d,J=6.3, 3H), 0.58 (s, 3H).

Step 9: Dissolve compound 376-5 (170 mg, 0.42 mmol, 1 eq) and diiodomethane (1.13 mg, 4.2 mmol, 10 eq) in toluene (1 mL) at room temperature. Add diethylzinc (2M in toluene) (2.1 ml, 4.2 mmol, 10 eq) dropwise at 0 ^° C. Stir at the same temperature for 1 hour and monitor the reaction by TLC (petroleum ether:ethyl acetate = 2:1). 100 mL of water was added to dilute at room temperature, and ethyl acetate (100 mL×2) was used for extraction. The organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain a white solid (4R)-4-[(1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-7-hydroxy-9a,11a-dimethyl-1,2,3,3a,3b,5,5a,6,7,8,9,9a,9b,10,11,11a-hexahydrospiro[cyclopenta[1,2-a]phenanthrene-4,1'-cyclopropane]-1-yl]pentanoic acid methyl ester 376-6 (160 mg, purity: 96.6%, yield: 90%). Compound 376-6 : ¹ H NMR (400 MHz, CDCl3) δ 3.66 (s, 3H), 3.63 – 3.55 (m, 1H), 2.37 – 2.17 (m, 2H), 1.94 (dt, J = 12.5,3.4 Hz, 1H), 1.88 – 1.70 (m, 6H), 1.61 –1.55 (m, 1H), 1.51 – 1.41 (m, 3H), 1.40 – 1.30 (m, 5H), 1.27 – 1.19(m, 2H), 1.14 – 0.95 (m, 4H), 0.87 (dd, J = 21.6, 10.2 Hz, 7H), 0.74 (dt, J = 8.9,4.4 Hz, 1H), 0.64 (s, 3H), 0.49(d, J = 3.5 Hz, 1H), 0.21 (dd, J = 13.5, 2.8 Hz, 1H), -0.02 (d, J = 4.2 Hz, 1H), -0.05 – -0.13 (m, 1H).

Step 9 : Dissolve 376-6 (110 mg, 0.264 mmol, 1 eq) in anhydrous tetrahydrofuran (5 mL) at room temperature. Under nitrogen protection, cool to 0 ^° C and add methylmagnesium bromide (2.5 M in 2-Me-THF, 1.1 mL, 2.64 mmol, 10 eq) dropwise. Then stir at room temperature for 2 hours. Monitor the reaction by TLC (petroleum ether: ethyl acetate = 2:1). After the reaction is completed, cool the system to 0 ^{°C and quench with saturated ammonium chloride aqueous solution (100 mL). Extract with ethyl acetate (100 mL×2). Add saturated saline (50 mL×100 mL) to the organic phase} . mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain a white solid (1R,3aS,3bR,5aS,7S,9aS,9bS,11aR)-1-[(2R)-5-hydroxy-5-methylhexan-2-yl]-9a,11a-dimethyl-1,2,3,3a,3b,5,5a,6,7,8,9,9a,9b,10,11,11a-hexadecahydrospiro[cyclopenta[1,2-a]phenanthrene-4,1'-cyclopropane]-7-ol 376 (80 mg, purity: 99.76 %, yield: 72 %). Compound 376 : ¹ H NMR (400 MHz, CDCl3) δ 3.59 (dd, J = 10.6, 5.1 Hz, 1H), 1.95 (dt, J = 12.6, 3.4 Hz, 1H), 1.90– 1.70 (m, 5H), 1.60 – 1.48 (m, 6H), 1.46 – 1.31(m, 7H), 1.29 – 1.22 (m, 2H), 1.19 (d, J = 1.3 Hz,6H), 1.15 – 0.96 (m, 5H), 0.92 (d, J = 6.6 Hz, 3H), 0.86 (s, 3H), 0.74 (dd, J = 9.0, 4.4 Hz,1H), 0.65(s, 3H), 0.54 – 0.43 (m, 1H), 0.21 (dd, J = 13.5, 2.8 Hz, 1H), -0.09 (dd, J = 9.3, 4.5 Hz, 1H). Example 378 Compound 378 Preparation of (1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-1-[(2R)-5- hydroxy -5- methylhexan -2- yl ]-9a,11a -dimethyl -1,2,3,3a,3b,5,5a,6,7,8,9,9a,9b,10,11,11a -hexahydrospiro [ cyclopenta [1,2-a] phenanthrene -4,1'- cyclopropane ]-6,7- diol

Step 1 : Dissolve the reactant 3β-hydroxycholan-5(6)-ene-24-oic acid methyl ester IV-4 (30 g, 77.2 mmol, 1.0 eq) in chloroform (180 mL), add selenium dioxide (21 g, 189.40 mmol, 2.5 eq), NMM (25.4 mL, 231.60 mmol, 3.0 eq) and stir the reaction system at 75 ^° C for 18 h. The reaction progress was monitored by TLC plate (petroleum ether: ethyl acetate = 5:1). 200 mL of water was added to the reaction system, extracted with ethyl acetate (100 mL x 3), the combined organic phases were washed with water (100 mL x 2), washed with saturated brine, dried over anhydrous sodium sulfate, and the organic phases were collected and concentrated to obtain a crude product. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 10:1 to 6:1 to 3:1) to obtain white solid 4β-hydroxy-3β-hydroxycholan-5(6)-ene-24-oic acid methyl ester 378-1 (20 g, purity 70%, yield 50.3%). Compound 378-1 : ¹ H NMR (400 MHz, CDCl3) δ 5.71 – 5.63 (m, 1H), 4.14 (d, J = 3.2 Hz, 1H), 3.66 (s, 3H), 3.56 (d, J = 11.5 Hz, 1H), 2.34 (dd, J = 10.2, 5.2 Hz,1H), 2.27 – 2.17 (m, 1H), 2.07 (s, 1H), 2.00 (d, J = 12.5 Hz, 1H), 1.89 (s, 1H), 1.88 – 1.78 (m, 3H), 1.65 – 1.51 (m, 4H), 1.46 – 1.39 (m, 3H), 1.36– 1.25 (m, 2H), 1.18 (s, 3H), 1.15 – 1.05 (m, 4H), 1.03 – 0.96 (m, 1H), 0.92 (d, J = 6.5 Hz, 4H), 0.68 (s, 3H).

Step 2 : Compound 378-1 (22.5 g, 55.6 mmol, 1.0 eq) was dissolved in acetone (300 mL), p-toluenesulfonic acid (6.70 g, 38.9 mmol, 0.7 eq) and 4A molecular sieve (5 g) were added, and the reaction system was stirred at room temperature for 2 hours. The reaction progress was detected by TLC plate (petroleum ether: ethyl acetate = 5:1). After the reaction was completed, 100 mL of water was added to the reaction system, and ethyl acetate (100 mL*3) was used for extraction. The organic phase was collected and washed with water (100 mL x 2), washed with saturated brine, dried with anhydrous sodium sulfate, and the organic phase was collected and concentrated to obtain a crude product. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 10:1 to 5:1) to obtain white solid (4R)-4-[(3aS,5aR,5bS,7aR, 8R,10aS,10bS,12bR)-2,2,5a,7a-tetramethyl-4,5,5a,5b,6,7,7a, 8,9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]pentanoic acid methyl ester 378-2 (19 g, purity 90%, yield 69%). Compound 378-2 : ¹ H NMR (400 MHz, CDCl3) δ 5.82 – 5.79 (m, 1H), 4.41 (d, J = 5.8 Hz, 1H), 3.66 (s, 3H), 2.35 (td, J = 10.2, 5.1 Hz, 1H), 2.23 (td, J = 9.6, 4.9 Hz, 1H), 2.12 (dd, J = 12.6, 4.5 Hz, 1H), 2.00 (dt, J = 12.4, 3.3 Hz, 1H), 1.95 – 1.77 (m, 2H), 1.76 – 1.69 (m, 1H), 1.63 (ddd, J = 10.5, 6.8, 4.3Hz, 4H), 1.53 (s, 5H), 1.49 – 1.37 (m, 2H), 1.35 (s, 3H), 1.28 (dd, J = 25.3, 21.7 Hz, 2H), 1.16 (s, 4H), 1.14 – 0.98 (m, 4H), 0.93 (d, J = 6.4 Hz, 4H), 0.69 (d, J = 4.6 Hz, 3H).

Step 3 : Dissolve compound 378-2 (19 g, 44.9 mmol, 1.0 eq) in acetone (200 mL), add N-hydroxyphthalimide (2.79 g, 17.0 mmol, 0.4 eq), tert-butyl hydroperoxide (20.5 mL, 213.6 mmol, 5.0 eq), cobalt acetate (1.5 g, 8.5 mmol, 0.2 eq), and stir the reaction system at 35 ^° C for 24 hours. Detect the reaction by TLC plate (petroleum ether: ethyl acetate = 5:1). Add water (100 mL) to the reaction system, and extract the aqueous layer with ethyl acetate (150 mL x 3). Combine the ethyl acetate layers and wash with saturated brine (50 mL x 3). The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 20:1 to 10:1 to 8:1) to give white solid (4R)-4-[(3aS,5aR,5bS,7aR,8R,10aS,10bS,12bR)-2,2,5a,7a-tetramethyl-11-oxyylidene-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12b-tetradecahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta-8-yl]pentanoic acid methyl ester 378-3 (10.5 g, purity 80%, yield 42.8%). Compound 378-3 : ¹ H NMR (400 MHz, CDCl3) δ 5.93 (s, 1H), 4.52 (d, J = 6.4 Hz, 1H), 4.33 (d, J = 5.8 Hz, 1H), 3.66 (d, J = 4.0 Hz, 3H), 2.36 (ddd, J = 15.3, 10.0,5.2 Hz, 3H), 2.26 – 2.17 (m, 1H), 2.07 – 1.88 (m, 3H), 1.81 (ddd, J = 9.6, 8.0, 3.1 Hz, 3H), 1.64 – 1.60 (m, 2H), 1.57 – 1.54 (m, 3H), 1.45 (dd, J =12.7, 9.9 Hz, 2H), 1.37 (s, 4H), 1.34 (d, J = 4.8 Hz, 5H), 1.20 – 1.07 (m, 3H), 0.93 (d, J = 6.4 Hz, 4H), 0.71 (s, 3H).

Step 4 : Compound 378-3 (10.5 g, 23.9 mmol, 1.0 eq) was dissolved in a mixed solution of methanol (300 mL) and ethyl acetate (100 mL), palladium carbon (4.0 g, 37.5 mmol, 40 wt%) was added, hydrogen was replaced three times, and the reaction system was stirred at 35 ^° C for 2 hours. The reaction progress was detected by TLC plate (petroleum ether: ethyl acetate = 5:1). The reaction was stopped when the raw material was consumed. The palladium carbon was filtered through diatomaceous earth, and the diatomaceous earth was washed with ethyl acetate (50 mL x 3). The organic phases were combined and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 20:1 to 10:1 to 6:1) to give a white solid (4R)-4-[(3aS,5aR,5bS,7aR,8R,10aS,10bS, 12aR,12bR)-2,2, 5a,7a-tetramethyl-11-oxyylidene-4,5,5a,5b, 6,7,7a,8,9,10,10a,10b,11,12, 12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]pentanoic acid methyl ester 3378-4 (6.2 g, Purity 80%, yield 44.8%). Compound 378-4 : ¹ H NMR (400 MHz, CDCl3) δ 4.06 – 3.95 (m, 2H), 3.66 (d, J = 2.9 Hz, 3H), 2.82 – 2.73 (m, 1H), 2.46 – 2.31 (m, 1H), 2.29 – 2.15 (m, 2H), 1.88 –1.75 (m, 1H), 1.70 – 1.59 (m, 2H), 1.54 (d, J = 5.8 Hz, 2H), 1.43 (ddd, J = 18.2, 12.4, 8.5 Hz, 2H), 1.34 – 1.27 (m, 4H), 1.13 – 0.98 (m, 2H), 0.92(d, J = 6.4 Hz, 2H), 0.66 (s, 1H).

Referring to Example 376 , by replacing 376-3 with 378-5 , (1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-1-[(2R)-5-hydroxy-5-methylhexan-2-yl]-9a,11a-dimethyl-1,2,3,3a,3b,5,5a, 6,7,8,9,9a,9b,10,11,11a-hexadecahydrospiro[cyclopenta[1,2-a]phenanthrene-4,1'-cyclopropane]-6,7-diol 378 (15.74 mg, 0.036 mmol, purity 98.11, yield 42.18%) was obtained. Compound 378 : ¹ H NMR (400 MHz, CDCl3) δ 3.17 (s, 1H), 3.07 (dd, J = 11.3, 3.4 Hz, 1H), 1.96 (t, J = 13.2 Hz, 1H), 1.50 (m, 2H), 1.31 (t, J = 14.2 Hz, 3H), 1.20 (s, 1H), 1.06(dd, J = 17.4, 10.8 Hz, 3H), 0.92 (dd, J = 22.8, 9.9 Hz, 8H), 0.71 (m, 10H), 0.62 (m, 3H), 0.45 (m, 7H), 0.25 (d, J = 4.2 Hz, 3H), 0.09 (s, 1H), -0.11 (d, J = 13.4Hz, 1H). LC-MS [MH] ^- = 631.45 Example 377 Preparation of Compound 377 (1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6- hydroxy -6- methylhept -2- yl ]-9a, 11a -dimethyl -1,2,3,3a, 3b, 5,5a, 6,7,8,9,9a,9b, 10,11,11a -hexahydrospiro [ cyclopenta [1,2-a] phenanthrene -4,1' - cyclopropane ]-6,7- diol

Step 1: Dissolve (5R)-5-[(1R,3aS,3bS,6R,7S,9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]hexanoic acid methyl ester I-8 (1 g, 2.17 mmol) in anhydrous tetrahydrofuran (20 mL) in a 10 mL round-bottom flask at room temperature. Cool the reaction mixture to 0 ^° C under nitrogen protection and add methylmagnesium bromide (7.23 mL, 21.70 mmol), then stirred at room temperature for 2 hours, and monitored by TLC (petroleum ether: ethyl acetate = 2: 1). After the reaction, the system was cooled to 0 ^o C, quenched with saturated aqueous ammonium chloride solution (60 mL), extracted with ethyl acetate (50 mL×3), and the organic phase was washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2: 1) to obtain white solid cholester-6(5)-ene-3β,4β,25-triol 377-1 (800 mg, yield: 79.38 %). Compound 377-1 : ¹ H NMR (400 MHz, CDCl3) δ 5.68 (d, J = 3.3 Hz, 1H), 4.14 (s, 1H), 3.56 (d, J = 11.1 Hz, 1H), 2.22 – 1.72 (m, 7H), 1.72 – 1.31 (m, 13H), 1.21 (s, 6H), 1.18 (s, 3H), 1.15 – 1.00 (m, 5H), 0.93 (d, J = 6.5 Hz, 3H), 0.68 (s, 3H).

Step 2 : Dissolve compound 377-1 (400 mg, 0.96 mmol) in tetrahydrofuran (15 mL) in a 100 mL round-bottom flask at room temperature, add triethylamine (2.9 g, 28.8 mmol), 4-dimethylaminopyridine (117 mg, 0.96 mmol) and acetic anhydride (980 mg, 9.6 mmol) at room temperature, then stir at 80°C for 24 hours, monitor the reaction by TLC (petroleum ether: ethyl acetate = 10:1), after the reaction is completed, quench with water (50 mL), extract with ethyl acetate (30 mL×3), saturated organic phase with brine (50 mL×40). The reaction mixture was washed with 4% paraformaldehyde (2% ethyl acetate) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 10:1) to obtain white solid acetate-(6R)-6-[(1R,3aS,3bS,6R, 7S,9aR,9bS,11aR)-6,7-diethoxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylhept-2-yl ester 377-2 (415 mg, yield: 71.76%). Compound 377-2 : ¹ H NMR (400 MHz, CDCl3) δ = 5.84 – 5.79 (m, 1H), 5.50 (d, J=2.5, 1H), 4.74 (dt, J=7.8, 4.1, 1H), 2.07 (s, 3H), 2.05 – 2.02 (m, 1H), 2.01 (s, 3H), 1.97 (s, 3H), 1.93 – 1.54 (m, 10H), 1.54 – 1.44 (m, 3H), 1.42 (s, 6H), 1.39 – 1.15 (m, 7H), 1.13 (s, 3H), 1.10 – 0.96 (m, 4H), 0.92 (d, J=6.5, 3H), 0.67 (s, 3H).

Step 3 : Dissolve compound 377-2 ( 200 mg, 0.398 mmol, 1.0 eq) in acetone (10 mL), add N-hydroxyphthalimide (12.98 mg, 0.080 mmol, 0.2 eq), tert-butyl hydroperoxide (0.318 mL, 1.591 mmol, 4.0 eq) and cobalt (II) acetate, anhydrous (3.52 mg, 0.020 mmol, 0.05 eq), and stir the resulting mixture in the reaction solution under N2 at 25°C for 18 h. The reaction progress was monitored by TLC plate (petroleum ether: ethyl acetate = 5:1). The starting material was completely consumed and a large polar point was generated. The mixture was diluted with ethyl acetate and quenched with saturated sodium sulfite. The aqueous layer was extracted with ethyl acetate (10 mL x 3). The ethyl acetate layers were combined and washed with saturated brine (10 mL). The ethyl acetate layer was dried over Na2SO4, filtered and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 80:20) to give (6R)-6-[(1R,3aS,3bS,6R,7S,9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethyl-4-oxylidene-2,3,3a,3b,4,6,7,8, 9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[1,2-a]phenanthren-1-yl]-2-methylhept-2-yl acetate 377-3 as a white solid (120 mg, yield 52.54%). Compound 377-3 : ¹ H NMR (400 MHz, CDCl3) δ 5.84 (s, 1H), 4.76 (d, J = 11.3 Hz, 1H), 4.37 (d, J = 2.5 Hz, 1H), 2.33 (dd, J = 22.1, 10.4 Hz, 2H), 2.12 (s, 3H), 1.97 (s, 4H), 1.70(m, 11H), 1.42 (s, 7H), 1.34 (m, 5H), 1.12 (m, 6H), 0.93 (d, J = 6.5 Hz, 3H), 0.69 (s, 3H).

Step 4: Dissolve compound 377-3 (150 mg, 0.290 mmol, 1.0 eq) in a mixed solvent of methanol (1 mL) and ethyl acetate (1 mL), add palladium carbon (30.89 mg, 0.290 mmol), and stir the resulting mixture under an atmosphere at 40°C for 1 h. The progress of the reaction was monitored by TLC plate (petroleum ether: ethyl acetate = 3:1). The raw material was completely consumed, and a small polar point was generated. The crude product was obtained by filtration and concentration. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 80:20) to give acetic acid-(6R)-6-[(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-7-acetyloxy-6-hydroxy-9a,11a-dimethyl-4-oxyylidenehexahydro-1H-cyclopenta[1,2-a]phenanthran-1-yl]-2-methylhept-2-yl 377-4 as a white solid (100 mg, yield 59.77%). Compound 377-4 : ¹ H NMR (400 MHz, CDCl3) δ 4.70 (dd, J = 7.7, 4.5 Hz, 1H), 3.80 (s, 1H), 2.89 (t, J = 13.4 Hz, 1H), 2.38 (t, J = 11.3 Hz, 1H), 2.22 (m, 1H), 2.10 (m, 4H), 1.99(m, 5H), 1.81 (m, 6H), 1.62 (m, 3H), 1.50 (ddd, J = 11.9, 5.9, 3.2 Hz, 3H), 1.43 (d, J = 8.1 Hz, 7H), 1.38 (m, 4H), 1.31 (s, 3H), 1.20 (m, 3H), 1.05 (m, 6H), 0.91 (d, J = 6.5 Hz, 3H), 0.65 (s, 3H).

Step 5: Dissolve the reactant methyltriphenylphosphonium bromide (309.89 mg, 0.867 mmol, 10.0 eq) in tetrahydrofuran (10 mL). Add 1.0 M potassium tert-butylate tetrahydrofuran solution (0.867 mL, 0.867 mmol, 10.0 eq) dropwise at 0°C under stirring. Return to room temperature and stir for 15 min before slowly adding compound 377-4 (90 mg, 0.173 mmol, 1.0 eq). After stirring at room temperature for 1 hour, monitor the reaction by TLC (petroleum ether: ethyl acetate = 1: 1). The starting material disappears and is completely converted into new spots. Quench with 100 mL of aqueous solution, extract with ethyl acetate (100 mL × 2), and the organic phase is washed with saturated brine (50 The residue was washed with 4% paraformaldehyde (20% sodium sulfate), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4: 1) to obtain acetic acid-(6R)-6-[(1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-6,7-dihydroxy-9a, 11a-dimethyl-4-methylidene hexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]-2-methylhept-2-yl 377-5 as a white solid (55 mg, purity 90%, yield 60.10%). Compound 377-5 : ¹ H NMR (400 MHz, DMSO) δ 4.64 (s, 1H), 4.53 (s, 1H), 4.32 (d, J = 6.1 Hz, 1H), 4.06 (d, J = 3.2 Hz, 1H), 3.52 (s, 1H), 3.28 (s, 1H), 2.36 (m, 1H), 1.94 (d, J =11.2 Hz, 2H), 1.91 (s, 3H), 1.82 (dt, J = 18.1, 9.0 Hz, 2H), 1.62 (m, 4H), 1.20 (m, 2H), 1.08 (s, 4H), 1.05 (s, 3H), 0.91 (d, J = 6.5 Hz, 4H), 0.64 (s, 4H).

Step 6: Dissolve compound 377-5 (50 mg, 0.105 mmol) in tetrahydrofuran (1 mL), methanol (1 mL) and water (0.5 mL). Add lithium hydroxide (25.22 mg, 1.053 mmol) dropwise at 0°C with stirring. Stir at 4°C overnight and monitor the reaction by TLC (petroleum ether: ethyl acetate = 3:1). The mixture was quenched with 10 mL of aqueous solution and extracted with ethyl acetate (10 mL×2). The organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain white solid 3β-hydroxy-7-methylidenecholan-24-oic acid methyl ester 7-methylidene-5α-cholest-3β,4β,25-triol 377-6 (40 mg, 0.083 mmol, yield 79.00%).

Step 7: Dissolve reactant 377-6 (55 mg, 0.116 mmol, 1.0 eq) and diiodomethane (185.70 mg, 0.693 mmol, 10.0 eq) in 4% paraformaldehyde. Add diethylzinc (85.63 mg, 0.693 mmol, 10.0 eq) dropwise at 0°C with stirring. Return to room temperature and stir for 60 min. Monitor the reaction by TLC (petroleum ether:ethyl acetate = 1:1). The mixture was quenched with 10 mL of aqueous solution and extracted with ethyl acetate (10 mL×2). The organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain a white solid (1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethyl-1,2,3,3a, 3b, 5,5a, 6, 7,8,9,9a,9b,10,11,11a-hexahydrospiro[cyclopenta[1,2-a]phenanthrene-4,1'-cyclopropane]-6,7-diol 377-7 (30 mg, purity 60%, yield 58.12%)

Step 8 Compound 377-7 (40 mg, 0.090 mmol, 1.0 eq) was dissolved in DCM (5 mL), and benzoyl chloride (0.031 mL, 0.269 mmol, 3.0 eq), triethylamine (0.037 mL, 0.269 mmol, 3.0 eq) and DMAP (10.94 mg, 0.090 mmol, 1.0 eq) were added. The reaction system was stirred at room temperature for 2 h. The reaction was detected to be complete by TLC plate (petroleum ether: ethyl acetate = 3:1). Ethyl acetate (50 mL) was added to the reaction system, washed with saturated ammonium chloride (25 mL), the organic phase was collected, dried with anhydrous sodium sulfate, filtered and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 80:20) to give a white crude product of benzoic acid-(1R,3aS,3bS,5aR,6R,7S, 9aR,9bS,11aR)-6-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-1,2,3,3a,3b,5,5a, 6,7,8,9,9a,9b,10,11,11a-hexadecahydrospiro[cyclopenta[1,2-i]phenanthrene-4,1'-cyclopropane]-7-yl ester 377-8 (30 mg, yield 54.74%). The crude product 377-8 was purified by chiral separation (y instrument: Waters Acquity UPCC; chromatography column: Daicel CHIRALPAK OJ_3, 3*150mm, 3um; mobile phase: A/B: CO2/MeOH (0.1% DEA) = 60/40; flow rate: 1.5 ml/min; column temperature: 37 degrees, retention time: 1.864min) to obtain benzoic acid-(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-6-hydroxy-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a,11a-dimethyl-1,2,3,3a,3b,5,5a,6, 7,8,9,9a,9b,10,11,11a-Hexadecahydrospiro[cyclopenta[1,2-i]phenanthrene-4,1'-cyclopropane]-7-yl ester 377-8 (20 mg, purity 90%, yield 60%). Compound 377-8 : ¹ H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.1 Hz, 2H), 7.56 (d, J = 7.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 5.00 (d, J = 13.4 Hz, 1H), 3.90 (s, 1H), 2.41 (t, J =13.0 Hz, 1H), 2.06 (dd, J = 17.7, 10.1 Hz, 1H), 1.91 (m, 3H), 1.40 (dd, J = 37.4, 10.8 Hz, 10H), 1.21 (s, 8H), 1.17 (s, 5H), 1.07 (m, 5H), 0.93 (d, J = 6.5 Hz, 3H), 0.84 (dd, J = 34.6, 8.3 Hz, 5H), 0.65 (s, 3H), 0.51 (s, 2H), 0.32 (d, J = 13.8 Hz, 1H).

Step 9 Compound 377-8 (20 mg, 0.036 mmol, 1.0 eq) was dissolved in a mixed solvent of methanol (1 mL), tetrahydrofuran (1 mL) and water (0.5 mL), and lithium hydroxide (4.35 mg, 0.182 mmol, 5.0 eq) was added. The reaction was complete by TLC plate (petroleum ether: ethyl acetate = 1:). DCM (10 mL) was added to the reaction system, washed with saturated ammonium chloride (5 mL), the organic phase was collected, dried with anhydrous sodium sulfate, filtered and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 60:40) to give a white solid (1R, 3aS, 3bS, 5aR, 6R, 7S, 9aR, 9bS, 11aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-9a, 11a-dimethyl-1,2,3,3a, 3b, 5,5a, 6,7,8,9,9a,9b, 10,11,11a-hexadecahydrospiro[cyclopenta[1,2-a]phenanthrene-4,1'-cyclopropane]-6,7-diol 377 (4.5 mg, purity 100%, yield 27.74%). Compound 377 : ¹ H NMR (400 MHz, CDCl3) δ 3.66 (s, 1H), 3.59 (s, 1H), 2.36 (dd, J = 13.2, 11.4 Hz, 1H), 1.95 (dd, J = 9.0, 3.2 Hz, 1H), 1.88 (t, J = 10.5 Hz, 1H), 1.74 (ddt, J =20.8, 17.0, 3.8 Hz, 3H), 1.48 (m, 2H), 1.33 (dd, J = 14.2, 6.5 Hz, 8H), 1.27 (d, J = 12.1 Hz, 3H), 1.21 (s, 6H), 1.14 (m, 1H), 1.09 (s, 3H), 1.00 (m, 4H), 0.92 (d, J =6.6 Hz, 3H), 0.84 (ddd, J = 20.6, 10.1, 4.6 Hz, 4H), 0.64 (s, 3H), 0.51 (d, J = 9.1 Hz, 1H), 0.31 (dd, J = 13.5, 2.6 Hz, 1H). LC-MS (ESI) [MH] ^- = 445.45 Example 379 Compound 379 Preparation of (1R,3bS,5aR,7S,9aR,9bS,11aR)-4,4 -difluoro -1-[(2R)-5- hydroxy -5- methylhexan -2- yl ]-9a,11a -dimethyl -1,2,3,3a,3b,4,5,5a,7,8,9,9a,9b,10,11,11a- hexahydrospiro [ cyclopenta [1,2-a] phenanthrene -6,1'- cyclopropane ]-7 - ol

In the first step , the reactant (4R)-4-[(3aS,5aR,5bS,7aR,8R, 10aS,10bS,12aR,12bR)-2,2,5a,7a-tetramethyl-11-oxyylidene-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopenta[8-yl]pentanoic acid methyl ester 377-4 (6.2 g, 13.5 mmol, 1 eq) was dissolved in diethylaminosulfur trifluoride (10 mL). The resulting mixture was stirred in the reaction solution at 80 ^° C for 1 hour. The reaction progress was monitored by TLC plate (petroleum ether: ethyl acetate = 10:1). The reaction solution was cooled to room temperature, dichloromethane (50 mL) was added to dilute the reaction system, and the reaction system was slowly added dropwise to ice water to quench. Dichloromethane (50 mL×3) was used for extraction, and the organic phase was collected and dried with anhydrous sodium sulfate. The organic phase was vacuum rotary dried to obtain a crude product. The crude product was dissolved in ethyl acetate and purified by column chromatography (petroleum ether:ethyl acetate = 30:1 to 20:1 to 15:1) to give a white solid (4R)-4-[(3aS,5aR,5bS,7aR,8R,10aS,10bS, 12aR,12bR)-11,11-difluoro-2,2,5a,7a-tetramethyl-4,5,5a,5b,6, 7,7a,8,9,10,10a,10b, 11,12,12a,12b-hexahydro-3aH-cyclopenta[1',2':1,2]phenanthro[7,8-d][1,3]dioxacyclopentan-8-yl]pentanoic acid methyl ester 379-1 (4.4 g, yield 54%). Compound 379-1 : ¹ H NMR (400 MHz, CDCl3) δ 4.13 – 3.98 (m, 2H), 3.66 (s, 3H), 2.29 (ddd, J = 16.0, 9.9, 5.8 Hz, 1H), 2.12 – 2.03 (m, 0H), 1.96 – 1.75 (m, 4H),1.74 – 1.57 (m, 2H), 1.51 (s, 2H), 1.41 (ddd, J = 16.1, 8.0, 5.5 Hz, 2H), 1.34 – 1.28 (m, 3H), 1.14 (dd, J = 12.9, 4.3 Hz, 1H), 1.08 (d, J = 5.8 Hz, 2H), 0.92 (d, J = 6.4 Hz, 2H), 0.70 – 0.63 (m, 2H).

Step 2: In a 100 mL round-bottom flask at room temperature, compound 379-1 (800 mg, 1.66 mmol) was dissolved in tetrahydrofuran (12 mL), and 3 mol aqueous hydrochloric acid solution (12 mL) was added dropwise. The mixture was then stirred at room temperature for 2 hours and the reaction was monitored by TLC (petroleum ether:ethyl acetate = 2:1). After the reaction was completed, saturated aqueous sodium bicarbonate solution (100 mL) was added to quench the reaction, and the mixture was extracted with ethyl acetate (60 mL×3). The organic phase was washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain white solid (4R)-4-[(1R,3aS,3bS,5aR,6R,7S,9aR,9bS,11aR)-4,4-difluoro-6,7-dihydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]pentanoic acid methyl ester 379-2 (620 mg, yield: 80.29 %). Compound 379-2 : ¹ H NMR (400 MHz, CDCl3) δ = 3.74 (s, 1H), 3.66 (s, 3H), 3.63 – 3.57 (m, 1H), 2.35 (ddd, J=15.3, 10.2, 5.1, 1H), 2.28 – 2.13 (m, 2H), 2.00 – 1.67 (m, 12H), 1.48 – 1.24 (m, 9H), 1.06 (s, 3H), 0.92 (d, J=6.4, 3H), 0.67 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -88.97 (d, J=236.0, 1F), -110.94 (d, J=236.0, 1F).

Step 3 : In a 100 mL round-bottom flask at room temperature, compound 379-2 (760 mg, 1.72 mmol) was dissolved in dichloromethane (15 mL), and triethylamine (521 mg, 5.15 mmol), 4-dimethylaminopyridine (63 mg, 0.51 mmol) and acetic anhydride (175 mg, 1.72 mmol) were added at room temperature, followed by stirring at room temperature for 1 hour. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 3:1). After the reaction was completed, the mixture was quenched with water (80 mL), extracted with ethyl acetate (60 mL×3), and the organic phase was saturated with brine (100 The reaction mixture was washed with 4% paraformaldehyde (20% ethyl acetate) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 3:1) to obtain white solid (4R)-4-[(1R,3aS,3bS,5aR,6R, 7S,9aR,9bS,11aR)-7-acetyloxy-4,4-difluoro-6-hydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]pentanoic acid methyl ester 379-3 (760 mg, yield: 82.19 %). Compound 379-3 : ¹ H NMR (400 MHz, CDCl3) δ = 4.73 (dd, J=9.4, 6.0, 1H), 3.83 (s, 1H), 3.66 (s, 3H), 2.41 – 2.15 (m, 3H), 2.09 (s, 3H), 2.00 – 1.63 (m, 12H), 1.50 –1.22 (m, 9H), 1.09 (s, 3H), 0.92 (d, J=6.3, 3H), 0.67 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -89.07 (d, J=236.4, 1F), -110.86 (d, J=236.4, 1F).

Step 4: Dissolve compound 379-3 (610 mg, 1.38 mmol) in dichloromethane (15 mL) in a 100 mL round-bottom flask at room temperature, add Dess-Martin periodinane (877 mg, 2.07 mmol) at room temperature, and stir at room temperature for 1 hour. Detect the reaction by TLC (ethyl acetate/petroleum ether = 5:1). After the reaction was completed, saturated aqueous sodium sulfite solution (60 mL) and saturated aqueous sodium bicarbonate solution (60 mL) were added to quench the reaction, and the mixture was extracted with dichloromethane (50 mL×3). The organic phase was washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, and the organic phase was concentrated and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain a white solid (4R)-4-[(1R, 3aS, 3bS, 5aR, 7S, 9aR, 9bS, 11aR)-7-acetyloxy-4,4-difluoro-9a, 11a-dimethyl-6-oxyylidene hexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]pentanoic acid methyl ester 379-4 (552 mg, yield: 81.82 %). Compound 379-4 : ¹ H NMR (400 MHz, CDCl3) δ = 5.18 (dd, J=12.2, 7.4, 1H), 3.67 (s, 3H), 2.53 (dd, J=10.6, 9.3, 1H), 2.41 – 2.19 (m, 3H), 2.15 (s, 3H), 2.10 – 1.78 (m, 8H), 1.64 – 1.08 (m, 12H), 0.93 (d, J=6.4, 3H), 0.79 (s, 3H), 0.67 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -90.64 (d, J=240.2, 1F), -111.79 (d, J=240.1, 1F).

Step 5: In a 100 mL round-bottom flask at room temperature, methyltriphenylphosphonium bromide (925 mg, 2.59 mmol) was suspended in tetrahydrofuran (10 mL), and a 1M/L potassium tert-butylate tetrahydrofuran solution (2.59 mL, 2.59 mmol) was added dropwise at 0°C. After the mixture was stirred at room temperature for 2 hours, a tetrahydrofuran (1.5 mL) solution of compound 379-4 (250 mg, 0.52 mmol) was added dropwise at 0°C. The mixture was stirred at room temperature for 4 hours. The reaction was detected by TLC (petroleum ether/ethyl acetate = 5:1), and a new compound was generated. After the reaction was completed, water (50 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (30 mL×3). The extracted organic solution was washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified and separated by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 5:1) to obtain a light yellow oily substance (4R)-4-[(1R,3aS,3bS,5aR,7S,9aR,9bS,11aR)-7-acetyloxy-4,4-difluoro-9a,11a-dimethyl-6-methylidene hexahydro-1H-cyclopenta[1,2-a]phenanthrene-1-yl]pentanoic acid methyl ester 379-5 (65 mg, yield: 18.27%). Compound 379-5 : ¹ H NMR (400 MHz, CDCl3) δ = 5.14 (dd, J=24.1, 12.4, 1H), 4.74 (s, 1H), 4.64 (s, 1H), 3.66 (s, 3H), 2.41 – 2.31 (m, 3H), 2.16 (s, 3H), 1.93 – 1.76 (m, 8H), 1.68 – 1.47 (m, 8H), 1.16 – 1.07 (m, 5H), 1.04 – 0.96 (m, 3H), 0.92 (dd, J=6.3, 2.0, 3H), 0.67 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -89.19 (d, J=238.5, 1F), -110.96 (d, J=238.6, 1F).

Step 6: Compound 379-5 (65 mg, 0.095 mmol, purity: 70 %) was dissolved in anhydrous tetrahydrofuran (2.5 mL) in a 50 mL round-bottom flask at room temperature. The reaction was cooled to 0 ^° C under nitrogen protection, and 3 mol/L methyl magnesium bromide tetrahydrofuran solution (0.32 mL, 0.95 mmol) was added dropwise. The mixture was stirred at room temperature for 2 hours and monitored by TLC (petroleum ether: ethyl acetate = 2:). After the reaction was completed, the system was cooled to 0 ^° C and quenched with saturated ammonium chloride aqueous solution (20 mL). The mixture was extracted with ethyl acetate (10 mL×3). The organic phase was saturated with brine (20 mL). mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2: 1) to obtain a white solid (1R, 3aS, 3bS, 5aR, 7S, 9aR, 9bS, 11aR)-4,4-difluoro-1-[(2R)-5-hydroxy-5-methylhexan-2-yl]-9a, 11a-dimethyl-6-methylidene hexadecahydro-1H-cyclopenta[1,2-a]phenanthrene-7-ol 379-6 (21 mg, purity: 90 %, yield: 45.52 %). Compound 379-6 : ¹ H NMR (400 MHz, CDCl3) δ = 4.86 (s, 1H), 4.72 (s, 1H), 3.84 (d, J=11.0, 1H), 2.42 (tdd, J=13.7, 5.7, 3.6, 1H), 2.32 – 1.60 (m, 14H), 1.57 – 1.32 (m, 10H), 1.18 (s, 6H), 0.89 – 0.84 (m, 6H), 0.61 (s, 3H). ¹⁹ F NMR (376 MHz, CDCl3) δ = -89.01 (d, J=237.8, 1F), -110.96 (d, J=237.8, 1F).

Step 7 Compound 379-6 (21 mg, 0.048 mmol) was dissolved in toluene (1 mL) in a 50 mL round-bottom flask at room temperature. Diiodomethane (129 mg, 0.48 mmol) and diethylzinc tetrahydrofuran solution (0.24 mL, 0.48 mmol) were added at 0°C. The mixture was stirred at room temperature for 16 hours. The reaction was monitored by TLC (petroleum ether: ethyl acetate = 2:). After the reaction was completed, water (10 mL) was added to quench the mixture. The mixture was extracted with ethyl acetate (10 mL × 3). The organic phase was saturated with brine (10 mL), dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 2:1) to obtain a white solid (1R,3bS,5aR,7S,9aR,9bS,11aR)-4,4-difluoro-1-[(2R)-5-hydroxy-5-methylhexan-2-yl]-9a,11a-dimethyl-1,2,3,3a,3b,4,5,5a, 7,8,9,9a,9b,10,11,11a-hexadecahydrospiro[cyclopenta[1,2-a]phenanthrene-6,1'-cyclopropane]-7-ol 379 (10.34 mg, purity: 95.57 %, yield: 64.5 %). Compound 379 : ¹ H NMR (400 MHz, CDCl3) δ = 3.63 (d, J=10.5, 1H), 2.43 – 2.31 (m, 1H), 2.04 – 1.96 (m, 2H), 1.92 – 1.67 (m, 5H), 1.62 – 1.31 (m, 16H), 1.20 (s, 6H), 0.93 (d, J=6.5, 3H), 0.91 (s, 3H), 0.68 (s, 3H), 0.66 – 0.62 (m, 1H), 0.61 – 0.56 (m, 1H), 0.21 – 0.16 (m, 1H), 0.10 – 0.06 (m, 1H). ¹⁹ F NMR (377 MHz, CDCl3) δ = -88.63 (d, J=237.1, 1F), -110.78 (d, J=237.1, 1F). LC-MS: [MH]- = 451.35. Effect Example 1 Inhibitory effect of the compounds of the present invention on the SREBP pathway 1.1 : SREBP luciferase reporter gene system

Huh-7/SRE-luc cells were incubated in a sterol-deficient medium (5% delipidated serum, 2 μM lovastatin, 10 μM mevalonic acid) and treated with corresponding concentrations of compounds for 16 hours. Huh-7/SRE-luc cells are cells that stably express LDLR promotor-luciferase and green fluorescent protein (GFP) in the human hepatoma cell line Huh-7. The cells were obtained by transfecting Huh-7 with pLDLR-promotor-luciferase and pEGFP-N1 plasmids and screening with G418 antibiotic selection pressure. Huh-7 cells were purchased from ATCC, pLDLR-promotor-luciferase plasmid was obtained by molecular cloning, and pEGFP-N1 plasmid was purchased from Addgene.

After the compound treatment, the cells were lysed with a lysis buffer (E397A, Promega), and after adding a luciferase substrate (E1500, Promega), the activity of SRE-driven luciferase was measured by a BioTek Synergy HTX enzyme marker (including but not limited to such an instrument). The fluorescence intensity of green fluorescent protein (EGFP) was also measured by the above-mentioned BioTek enzyme marker (including but not limited to such an instrument) and used as an internal reference. The ratio of the SRE-driven luciferase activity divided by the fluorescence intensity of green fluorescent protein was used as an indicator of the activity of the SREBP pathway. The test data of each test compound was analyzed by Prism software (the compound inhibition rate was calculated with the DMSO treatment group as a reference, and the Prism log (inhibitor) VS. response--Variable slope (four-parameter) model was used for fitting, and the calculation formula was: Y = Bottom + (Top-Bottom) / (1 + 10^ ((LogIC50-X) * HillSlope))), and the IC50 parameter of the compound was obtained. 1.2 Inhibitory effect of the compounds of the present invention on the SREBP pathway

The inhibitory effect of the compounds of the present invention on the SREBP pathway was tested by the method of biological test Example 1.1, and the concentration gradient of each compound was designed to be 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 10 μM, and the control was the solvent DMSO. The IC ₅₀ values of some compounds are shown in Table 1. Table 1 Implementation ID Structural SRE-luciferase assay (IC50 μ M) 13 1.350 twenty three 6.51 twenty four 0.07 25 0.15 26 0.5306 33 0.190 34 0.080 41 0.070 53 0.844 55 0.350 60 0.236 65 0.488 66 0.325 79 0.5129 85 or 0.205 86 or 0.1308 94 0.3732 103 0.3248 106 0.0857 109 1.175 114 1.131 118 0.30 121 0.779 122 1.482 123 0.32 125 2.578 137 0.17 138 0.083 139 0.205 143 8.16 144 1.722 158 0.2366 159 0.1868 160 4.257 9 1.230 10 17.02 12 14.2 14 7.99 18 2.45 19 2.70 27 19.23 29 3.196 31 0.74 56 1.212 59 1.814 61 0.621 162 1.214 170 0.472 300 0.024 173 1.524 178 0.210 179 2.628 180 or 0.228 181 or 0.174 185 0.191 186 0.357 187 0.161 196 0.331 208 or 0.541 209 or 0.668 219 0.229 376 0.43 377 0.211 378 0.75 379 6.825 Effect Example 2 : Mouse liver microsome metabolic stability experiment

PB solution (100 mM), MgCl2 solution (300 mM), NADPH solution (2.04 mM) and mouse liver microsome (SHQY Cat. No.: M1000 Batch No.: 2110330) solution (1.00 mg/mL) were prepared respectively, and then compound and testosterone (positive control, half-life of 3.1 minutes) stock solutions were prepared with dimethyl sulfoxide (DMSO), diluted to 100 µM with methanol for sample incubation, and stored at -10~ -30℃. Then 100 µL of mouse liver microsome solution was added to the 96-well sample plate. For the 0 min sample, acetonitrile solution containing internal standard was added first; then 2 µL of 100 µM working solution was added; and then 98 µL of 2.04 mM NADPH preheated to 37°C was added. For samples at 5 min, 15 min, 30 min, 45 min, and 60 min, 2 µL of 100 µM working solution was first added; then 98 µL of 2.04 mM NADPH preheated to 37°C was added to start the reaction; after reaching the corresponding time point, acetonitrile solution containing the internal standard was added to terminate the reaction. For samples of NCF60, 2 µL of 100 µM working solution was first added; then 98 µL of PB preheated to 37°C was added to start the reaction; after reaching the corresponding time point, acetonitrile solution containing the internal standard was added to terminate the reaction. During the experiment, the samples were incubated in a 37°C water bath. All samples were shaken on a shaker at 800 rpm for 10 min and then centrifuged at 3200 g for 20 min. The supernatant was aspirated, diluted with deionized water in the corresponding ratio, and then analyzed by LC-MS/MS. The residual rate of the compound at each time point was obtained by dividing the peak area ratio of the compound at 5, 15, 30, 45 and 60 min by the peak area ratio at 0 min, and then the half-life (T1/2) of the compound was calculated using Excel. Table 2: Mouse liver microsome stability results of the compounds of some examples Embodiment Mouse liver microsome half-life (minutes) Comparative compound 1 7.85 25 17.305 33 11.40 85 98.86 86 18.84 94 >186 103 176 114 37.1 119 97.5 29 45.57 12 ＞184.78 59 ＞184.78 Effect Example 3 : Testing the solubility of the compounds of the present invention in fasting state simulated intestinal fluid (FaSSIF)

Dissolve the compound powder in DMSO and prepare a 10.0 mM stock solution for later use. Weigh 0.021 g NaOH, 0.198 g NaH2PO4, and 0.309 g NaCl, add to 50.0 mL ultrapure water, mix well, adjust the pH to 6.5 with HCl or NaOH, then add 0.112 g FaSSIF powder, wait for complete dissolution and let stand at room temperature for 2 hours for later use. Take a certain volume of the compound stock solution and add it to a certain volume of FaSSIF to prepare a 300 µM sample solution, mix at room temperature and 1000 rpm for 1 hour. After 1 hour, centrifuge the sample and take a certain volume of the supernatant, add the stop solution, precipitate the sample, mix well, and centrifuge for 20 minutes. Then the supernatant was taken and diluted with diluent and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentration of the test compound in the sample was quantitatively determined by LC-MS/MS. Table 3: FASSIF solubility results of some examples of compounds Embodiment FASSIF Solubility μM 25 171 33 86.4 34 55.9 Effect Example 4 : Compound Inhibition Experiment on FASN Gene Expression

Huh-7 cells (purchased from ATCC) were cultured in DMEM medium (containing 10% fetal bovine serum LONSERA S711-001S) at 37°C in a 5% CO2 incubator. After 24 hours, the original medium was removed and replaced with DMEM starvation medium (containing 5% lipoprotein-free serum (LPDS), 2 µM lovastatin, 10 µM mevalonate). The control group was added with dimethyl sulfoxide (DMSO), and the compound-treated group was added with different concentrations of compounds. The highest concentration of the compound was 3000nM, and it was diluted 3 times, with a total of 5 concentrations. The culture was continued for 16 hours. Cell lysis, cell to cDNA reverse transcription, and qPCR detection of SREBP target gene fatty acid synthase (FASN) gene expression (FASN gene forward primer sequence: 5'-AAGGACCTGTCTAGGTTTGATGC-3', reverse primer sequence: 5'-TGGCTTCATAGGTGACTTCCA-3'), IC50 was calculated. The test data of each test compound were analyzed by prism software (the compound inhibition rate was calculated with the DMSO treatment group as a reference, and the Prism log (inhibitor) VS. response--Variable slope (four-parameter) model was used for fitting, and the calculation formula was Y=Bottom + (Top-Bottom)/(1+10^((LogIC50-X)*HillSlope))), and the IC50 parameter of the compound was obtained. Table 4: Inhibition results of some compounds of the examples on FASN gene expression Embodiment FASN IC50 A:＜200 nM; B:200-500 nM; Comparative compound 1 959 nM twenty four B 25 B 55 B 60 B 85 B 86 A 94 A 123 A 138 A 180 A 181 A

In the present invention, the structure of comparative compound 1 is Effect Example 5: Microsomal stability in mice, rats, dogs and humans

1 µM of the test compound or verapamil (positive control) was incubated with 0.5 mg/mL of (mouse, rat, dog and human) liver microsomes in 1 mM NADPH with and without added cofactors. After incubation at 37°C for 0.5, 5, 15, 30 and 60 minutes, the reaction was terminated by adding the internal standard solution. All samples were centrifuged, and the samples were analyzed by UPLC-MS/MS and the percentage remaining, in vitro intrinsic clearance (in vitro CLint) and half-life (t1/2) were calculated.

The compounds of the present invention have good metabolic stability in mouse, rat, dog and human liver microsomes. Effect Example 6: Stability in mouse, rat, dog, monkey or human liver cells

1 μM test substance or verapamil (positive control) was incubated with incubation medium containing mouse, rat, dog, monkey or human hepatocytes (0.5 × 106 cells/mL). After incubation at 37°C for 0.5, 15, 30, 60, 90, and 120 minutes, the reaction was terminated by adding internal standard solution. All samples were centrifuged and the supernatant was aspirated. The samples were analyzed by UPLC-MS/MS and the residual percentage, intrinsic clearance (in vitro CLint) and half-life (t1/2) were calculated.

The compounds of the present invention have good metabolic stability in mouse, rat, dog, monkey and human liver cell microsomes. Effect Example 7: CYP Inhibition

The inhibitory potential of the test compounds on cytochrome P450 enzymes 1A2, 2C9, 2C19, 2D6 and 3A4 was evaluated using a 0.1 M phosphate buffer (pH 7.4) system containing 0.2 mg/mL human liver microsomes. The test compounds were co-incubated with specific substrates for different reaction times (20, 5, 20, 20, 5 and 10 minutes for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4-M and CYP3A4-T systems, respectively). After the incubation time, all samples were immediately added with internal standard solution to terminate the reaction. All samples were centrifuged and the supernatant was taken out. The metabolites formed by the specific substrate were detected by UPLC-MS/MS, and the half-inhibitor concentration (IC50) of the specific substrate metabolism was calculated.

The compounds of the present invention have weak inhibitory ability on cytochrome P450 enzymes 1A2, 2C9, 2C19, 2D6 and 3A4. Effect Example 8: Mouse PK test C57BL/6JL

C57BL/6J mice, 6-8 weeks old, 3 males per group, were administered intravenously, or intraperitoneally for pharmacokinetic studies of new molecules. Animals were fasted before drug administration and given food 4 hours after drug administration. Whole blood was collected at 5min, 15min, 0.5h, 1h, 2h, 4h, 8h, 12h, and 24h after drug administration. Plasma was obtained after centrifugation and concentration was detected using LCMSMS. Pharmacokinetic parameters were calculated using WinNonlin (PhoenixTM, version 8.3) or higher.

The compound of the present invention has a relatively low systemic clearance rate after intravenous administration in mice , and has good oral and intraperitoneal bioavailability.

SD rats, 6-8 weeks old, 3 males per group, were used for pharmacokinetic study of new molecules via intravenous, oral or intraperitoneal injection. The animals were fasted before drug administration and given food 4 hours after drug administration. Whole blood was collected at 5min, 15min, 0.5h, 1h, 2h, 4h, 8h, 12h, and 24h after drug administration. Plasma was obtained after centrifugation and concentration was detected using LCMSMS. Pharmacokinetic parameters were calculated using WinNonlin (PhoenixTM, version 8.3) or higher.

The compound of the present invention has a lower systemic clearance rate after intravenous administration in rats, and has better oral and intraperitoneal bioavailability.

Although the specific implementations of the present invention are described above, those skilled in the art should understand that these are only examples, and that various changes or modifications may be made to these implementations without departing from the principles and essence of the present invention. Therefore, the scope of protection of the present invention is limited by the scope of the attached patent application.

TW202508555A_113127742_SEQL.xml

Claims (10)

A compound represented by formula I, II or III or a pharmaceutically acceptable salt thereof: wherein R ^4a is H; R ^4b is halogen, CN, -CH ₂ -CN, -CH ₂ -OH, -CH(CH ₃ )-OH, -COOH, -CH ₂ -COOH, C ₁ -C ₆ halogenated alkyl, -CH ₂ -OAc or NH ₂ ; or R ^4a and R ^4b and the carbon atoms to which they are connected together form or ; When there is a single bond between carbon atom No. 7 and carbon atom No. 8, R ^7a and R ^7b are independently H, halogen, CN, -CH ₂ -OH, -COOH, -CH ₂ -COOH, NH ₂ , C ₁ -C ₆ alkyl, C ₁ -C ₆ halogenated alkyl or -CH ₂ -CN; or, R ^7a and R ^7b and the carbon atoms to which they are connected together form , , or ; R ^8a is H; When there is a double bond between carbon atoms 7 and 8, R ^7a does not exist, R ^7b is a halogen; R ^8a does not exist; R ²¹ is , , , or ; n1 and n3 are independently 2, 3, 4 or 5; m1 and m3 are independently 0, 1, 2, 3, 4 or 5; Ring A and Ring C are independently C ₆ -C ₁₀ aryl, "a 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S" or C ₃ -C ₆ cycloalkyl; ^RA and ^RC are independently halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ halogenated alkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ halogenated alkoxy; R ¹ is or NR ^1a R ^1b ; R ^1a and R ^1b are independently H or C ₁ -C ₆ alkyl; R ^4c is H; R ^4d is H or OH; R ^7c is H, and R ^7d is independently CN, -CH ₂ -OH, -COOH, C ₁ -C ₆ alkyl, C ₁ -C ₆ halogenated alkyl, -CH ₂ -COOH, NH ₂ , -CH ₂ -CN or Cl; or, R ^7c and R ^7d and the carbon atoms to which they are connected together form , , or ; R ²² is , , or ; n2 is 2, 3, 4 or 5; m2 is 0, 1, 2, 3, 4 or 5; Ring B is C ₆ -C ₁₀ aryl, "a 5-10 membered heteroaryl having 1, 2 or 3 heteroatoms selected from N, O and S" or C ₃ -C ₆ cycloalkyl; ^RB is independently halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ halogenated alkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ halogenated alkoxy; R ^3a is H or C ₁ -C ₆ alkyl; in R ^3a , the C ₁ -C ₆ alkyl is methyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; R ^3b is -O-(CH ₂ )nR ^3-1 , NR ^3-2 R ^3-3 or OH; when R ^3b is OH, R ^3a is C ₁ -C ₆ alkyl; n is 1, 2, 3 or 4; R ^3-1 is OH or -C(O)OR ^3-1a ; R ^3-1a is H or C ₁ -C ₆ alkyl; R ^3-2 and R ^3-3 are independently H or -S(O) ₂ R ^3-2a ; R ^3-2a is C ₁ -C ₆ halogenated alkyl or C ₁ -C ₆ alkyl; R ^4e is H; R ^4f is H, OH or -O-(CH ₂ )mOR ^4-1 ; or R ^4e and R ^4f and the carbon atoms to which they are connected together form ; m is 1 or 2; R ^4-1 is C ₁ -C ₆ alkyl; A carbon atom with "*" indicates that when it is a chiral carbon atom, it is independently in R configuration, S configuration or a mixture of the two; A carbon atom with "#" indicates that when it is a chiral carbon atom, it is independently in R configuration, S configuration or a mixture of the two; A carbon atom with "&" indicates that when it is a chiral carbon atom, it is independently in R configuration, S configuration or a mixture of the two; The compound shown in formula I is not the following compound: , and , and isomers thereof; The compound shown in formula II is not the following compound: and isomers thereof; The compound shown in formula III is not the following compound: and , and its isomers. The compound of formula I, II or III or a pharmaceutically acceptable salt thereof as described in claim 1 is characterized in that one or more of the following conditions are satisfied: (1) in R ^4b , the halogen is independently F, Cl, Br or I; for example, Br; (2) in R ^4b , the C ₁ -C ₆ halogenated alkyl is independently CHF ₂ , CH ₂ F or CF ₃ ; (3) in R ^7a and R ^7b , the halogen is independently F, Cl, Br or I; preferably F; (4) in R ^7a and R ^7b , the C ₁ -C ₆ alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; (5) in R ^7a and R ^7b , the C ₁ -C 6 halogenated alkyl is independently CHF 2 , CH 2 F or CF 3 ₆ halogenated alkyl groups are independently CHF ₂ , CH ₂ F or CF ₃ , such as CHF ₂ ; (6) In Ring A and Ring C, the C ₆ -C ₁₀ aryl groups are independently phenyl or naphthyl, preferably phenyl; (7) In Ring A and Ring C, the “heteroatoms selected from 1, 2 or 3 of N, O and S, 5-10 membered heteroaryl groups having 1, 2 or 3 heteroatoms” are independently “heteroatoms selected from 1, 2 or 3 of N, O and S, 5-6 membered or 9-10 membered heteroaryl groups having 1 or 2 heteroatoms”, such as pyridyl (e.g. , or ); (8) In Ring A and Ring C, the C ₃ -C ₆ cycloalkyl group is independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; (9) In ^RA and ^RC , the halogen group is independently F, Cl, Br or I; preferably F or Cl, such as F; (10) In ^RA and ^RC , the C ₁ -C ₆ alkyl group is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; (11) In ^RA and ^RC , the C ₁ -C ₆ halogenated alkyl group is independently CHF ₂ , CH ₂ F or CF ₃ ; (12) In ^RA and ^RC , the C ₁ -C wherein the C 1 -C ₆ alkoxy group is independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, preferably methoxy or ethoxy; (13) in RA and ^RC , the C ₁ -C ₆ halogenated alkoxy group is independently -OCHF ₂ , -OCH ₂ F or -OCF ₃ ; preferably -OCF ₃ ; (14) in R ^1a and R ^{1b ,} the C ₁ -C ₆ alkyl group is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example, methyl; (15) in Formula I, the carbon atom with "*" indicates that when it is a chiral carbon atom, it is in S configuration; (16) in R ^7c and R ^7d , the C ₁ -C 6 halogenated alkoxy group is independently -OCHF 2 , -OCH 2 F or -OCF 3 ; preferably -OCF 3 ; In R ^7c and R ^7d , the C ₁ -C ₆ halogenated alkyl group is independently CHF ₂ , CH ₂ F or CF ₃ , for example CHF ₂ ; (18) In ring B, _the C ₆ -C ₁₀ aryl group is phenyl or naphthyl, preferably phenyl; (19) In ring B, the “heteroatoms selected from 1, 2 or 3 of N, O and S, 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms” is “heteroatoms selected from 1, 2 or 3 of N, O and S, 5-6 membered or 9-10 membered heteroaryl group having 1 or 2 heteroatoms”, for example, pyridyl (for example , or ); (20) in ring B, the C ₃ -C ₆ cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; (21) in ^RB , the halogen is independently F, Cl, Br or I; preferably F or Cl, such as F; (22) in ^RB , the C ₁ -C ₆ alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; (23) in ^RB , the C ₁ -C ₆ halogenated alkyl is independently CHF ₂ , CH ₂ F or CF ₃ ; (24) in ^RB , the C ₁ -C wherein the C 1 -C ₆ alkoxy group is independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, preferably methoxy or ethoxy; (25) in R ^B , the C ₁ -C ₆ halogenated alkoxy group is independently -OCHF ₂ , -OCH ₂ F or -OCF ₃ , preferably -OCF ₃ ; (26) in formula II, the carbon atom with "*" indicates that it is an S configuration when it is a chiral carbon atom; (27) in formula II, the carbon atom with "#" indicates that it is an R configuration when it is a chiral carbon atom; (28) in R ^3-1a , the C ₁ -C ₆ alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example, tert-butyl; (29) in R ^3-2a , the C _{1 -C 6} alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, for example, tert-butyl; -C ₆ halogenated alkyl is CHF ₂ , CH ₂ F or CF ₃ , such as CF ₃ ; and (30) in R ^4-1 , the C ₁ -C ₆ alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, such as ethyl. The compound of formula I, II or III or a pharmaceutically acceptable salt thereof as described in claim 1 is characterized in that it satisfies one or more of the following conditions: (1) In formula I, for , or ; (2) R ^4a is H; R ^4b is a halogen (e.g., Br), CN, -CH ₂ -CN, -CH ₂ -OH, -CH(CH ₃ )-OH, -COOH, -CH ₂ -COOH, -CH ₂ -OAc, or NH ₂ ; or, R ^4a and R ^4b together with the carbon atoms to which they are attached form or ; (3) When there is a single bond between carbon atom No. 7 and carbon atom No. 8, R ^7a and R ^7b are independently H or halogen (e.g., F), preferably, R ^7a and R ^7b are both H or halogen (e.g., F); (4) When there is a double bond between carbon atom No. 7 and carbon atom No. 8, R ^7a does not exist, R ^7b is halogen (e.g., F); R ^8a does not exist; (5) R ²¹ is , or ; (6) Ring A and Ring C are independently C ₆ -C ₁₀ aryl or "a 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S"; (7) ^RA and ^RC are independently halogen, C ₁ -C ₆ alkoxy or C ₁ -C ₆ halogenated alkoxy; (8) n1 is 3; (9) n3 is 3; (10) m1 is 0, 1, 2 or 3; (11) m3 is 0, 1, 2 or 3; (12) In Formula II, for or ; (13) R ^7c is H, R ^7d is independently CN, -CH ₃ , -CH ₂ -OH, -COOH, -CHF ₂ , -CH ₂ -COOH, NH ₂ , -CH ₂ -CN or Cl; or, R ^7c and R ^7d together with the carbon atom to which they are attached form , , or ； (14) R ²² is , or ; (15) Ring B is a C ₆ -C ₁₀ aryl group or a "5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S"; (16) ^RB is independently a halogen, a C ₁ -C ₆ alkoxy group or a C ₁ -C ₆ halogenated alkoxy group; (17) n2 is 3; (18) m2 is 0, 1, 2 or 3; (19) In Formula III, for , , , , , or ; (20) n is 1, 2 or 3; (21) R ^3-2 is H, R ^3-3 is -S(O) ₂ R ^3-2a ; and (22) m is 1. The compound of formula I, II or III or a pharmaceutically acceptable salt thereof as described in claim 1 is characterized in that one or more of the following conditions are satisfied: (1) R ^4a is H; R ^4b is Br, CN, -CH ₂ -CN, -CH ₂ -OH, -CH(CH ₃ )-OH, -COOH, -CH ₂ -OAc or NH ₂ ; or, R ^4a and R ^4b together with the carbon atoms to which they are connected form ; (2) When there is a single bond between carbon atoms 7 and 8, R ^7a and R ^7b are both H or halogen (e.g., F); (3) R ^7c is H, and R ^7d is independently CN, -CH ₂ -OH, -CH ₃ , NH ₂ , -CH ₂ -CN, -CF ₂ H, -COOH, or R ^7c and R ^7d and the carbon atoms to which they are connected together form or ； (4) R ^3a is H, R ^3b is , 、-NH ₂ 、 , , , ; or, R ^3a is methyl, R ^3b is OH; and (5) R ^4e is H; R ^4f is H, OH or ; or R ^4e and R ^4f together with the carbon atoms to which they are attached form . The compound of formula I, II or III or a pharmaceutically acceptable salt thereof as described in claim 1 is characterized in that it satisfies one or more of the following conditions: (1) for , , , , , , , , , , , , or ; (2) for , , , , , , or ; (3) In Formula I, for , , , , , , , , , , , , , , , , , or ； (4) for , , , , , , , , , , , , , , , , , , or ; (5) In formula II, for , , , , , , , , , , , , , , , , or ; and (6) In formula III, for , , , , , , , , , , or . The compound of formula I, II or III or a pharmaceutically acceptable salt thereof as described in claim 1 is characterized in that it satisfies one or more of the following conditions: (1) R ²¹ is , , , , , , , , , , , , , , , , , , , , , or ; and (2) R ²² is , , , , , , , , , , , , , , , , , , , , , or . A compound as shown below or a pharmaceutically acceptable salt thereof: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or . A pharmaceutical composition comprising the compound as described in any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutical excipient. A use of a compound as described in any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition as described in claim 8 in the preparation of a medicament for preventing and/or treating a disease, wherein the disease is obesity, hyperlipidemia, fatty liver, diabetes, atherosclerosis, cardiovascular and cerebrovascular diseases, liver cancer or skin damage. A use of the compound according to any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof or the pharmaceutical composition according to claim 8 in the preparation of a drug for inhibiting the SREBP pathway.