CN120829375A

CN120829375A - Asymmetric disulfide compound containing sulfoxide group, preparation method and application thereof

Info

Publication number: CN120829375A
Application number: CN202410454392.2A
Authority: CN
Inventors: 万谦; 曾静; 孟令奎; 周思成; 吴品儒
Original assignee: Huazhong University of Science and Technology
Current assignee: Huazhong University of Science and Technology
Priority date: 2024-04-16
Filing date: 2024-04-16
Publication date: 2025-10-24

Abstract

The invention belongs to the technical field of chemical synthesis, and discloses an asymmetric disulfide compound containing sulfoxide groups, a preparation method and application thereof, wherein the asymmetric disulfide compound containing sulfoxide groups has a structure shown in a structural general formula (I). The invention improves the structure of the compound and the preparation method thereof, the obtained compound shown in the general formula (I) has novel structure and stable property, the preparation method has the advantages of cheap and easily obtained raw materials, simple operation, high reaction yield, convenient separation and purification of intermediates and products, suitability for industrial production and high preparation efficiency. In addition, the compound shown in the structural general formula (I) can be particularly used as an activating reagent in glycosylation reaction, is simple and convenient to operate in glycosylation reaction, has high reaction activity, and can be widely applied to activation of thioglycoside and selenoside to construct various substrates such as oxyglycoside, phenolic glycoside, ester glycoside, nucleoside, and carboside.

Description

Sulfoxide group-containing asymmetric disulfide compound, and preparation method and application thereof

Technical Field

The invention belongs to the technical field of chemical synthesis, and in particular relates to an asymmetric disulfide compound containing sulfoxide groups, a preparation method and application thereof.

Background

Glycosylation refers to the reaction of a glycosyl donor (a glycosyl unit with a leaving group introduced by exo-derivative) with a glycosyl acceptor (a glycosyl unit with a nucleophilic site or a non-aglycone) via an acetal or ketal linkage under the action of an activating reagent. Among these, nucleophilic sites may be oxygen, nitrogen, carbon, sulfur, etc., and acetal or ketal bonds formed during the reaction are also referred to as glycosidic bonds.

Among the numerous glycosyl donors, the thio-glycoside and selenoside donors are the most commonly used glycosyl donors because of the advantages of stability, easy acquisition, multifunction, convenient regulation of reaction activity and the like. The mixed anhydride represented by aryl sulfenate triflic anhydride (ArSOTf) is a class of highly efficient thioglycoside/selenoside activating reagent, which can achieve efficient activation of low activity donors with equivalent reagent (J.Am. Chem. Soc.1998,120, 435-436). However, arSOTf has poor stability and is generally produced in situ by aryl sulfenate (ArSCl) and silver triflate (AgOTf) and is now available. Most ArSCl, however, also have limited stability, are easily oxidized, quickly decomposed when meeting water, are not storable, and have strong irritating malodor, and in addition, agOTf is a noble metal reagent, is sensitive to light and has strong hygroscopicity. The above disadvantages limit the widespread use of this activation system. Thus, sugar chemists have been working on finding alternatives to this class of sulfenate triflic anhydride activating reagents or precursors thereof.

It is one of the important directions to develop stable sulfinyl derivatives to form an activation system with trifluoromethanesulfonic anhydride (Tf ₂ O). To date, various sulfinyl reagents have been developed, such as p-methoxyphenyl thiobenzene sulfinate MPBT (org. Lett.2000,2, 4067-4069), 1- (phenylsulfinyl) piperidine BSP (J. Am. Chem. Soc.2001,123, 9015-9020), diphenylsulfoxide Ph ₂ SO (org. Lett.2003,5, 1519-1522), and phenylsulfinyl morpholine BSM (Synlett 2006,17,2846-2850). However, the reaction effect of the above reagent is still different from that of the intermediate (RSOTf) of the triflic acid anhydride. In addition, the use of such agents for the activation of a thioglycoside/selenoside donor often requires the use of equivalent or even large excess amounts of the activating agent. Disulfide compounds may also be used as activating agents (org. Lett.2007,9, 4647-4650). However, compounds having both sulfinyl and disulfide functions are not shown to be useful as activating reagents for glycosylation reactions. The applicant reports that a compound VII simultaneously containing sulfoxide, disulfide bond and thioether functional groups can activate a high-activity sulfanyloside donor under the action of trifluoro methanesulfonic anhydride Tf ₂ O, but has weaker activation capability and limited application. (J.am.chem.Soc.2020, 142, 5498-5503). In addition, reagent VII is not suitable for a continuous one-pot glycosylation method constructed by sequentially adding an activating agent and a plurality of glycosidic bonds. As can be seen, compound VII is still not an ideal sulfan activating reagent.

Disclosure of Invention

Aiming at the defects or improvement demands of the prior art, the invention aims to provide an asymmetric disulfide compound containing sulfoxide groups, a preparation method and application thereof, and the structure and the preparation method of the compound are improved to obtain the asymmetric disulfide compound containing sulfoxide groups, which is shown in the general formula (I), and has the advantages of novel structure, stable property, low-cost and easily-obtained raw materials, simple operation, high reaction yield, convenient separation and purification of intermediates and products, suitability for industrial production and high preparation efficiency. In addition, the compound shown in the structural general formula (I) can be particularly used as an activating reagent in glycosylation reaction, is simple and convenient to operate in glycosylation reaction, has high reaction activity, and can be widely applied to activation of thioglycoside and selenoside to construct various substrates such as oxyglycoside, phenolic glycoside, ester glycoside, nucleoside, and carboside.

In order to achieve the above object, according to one aspect of the present invention, there is provided an asymmetric disulfide compound containing a sulfoxide group, characterized by having a structure as shown in the general structural formula (I):

Wherein S is a sulfur atom, and O is an oxygen atom;

r ¹ is selected from methyl, ethyl, isopropyl, phenyl, 4-methylphenyl and

R ² is selected from the group consisting of methyl, ethyl, benzyl, 4-methoxybenzyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 2, 3-dimethoxyphenyl, 4-nitrophenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl and 4-bromophenyl;

X is selected from And (CH ₂)₂).

As a further preferred aspect of the present invention, the structural formula of the sulfoxide group-containing asymmetric disulfide compound is specifically any one of structural formulas I-01 to I-31:

According to another aspect of the present invention, there is provided a process for producing the above-mentioned sulfoxide group-containing asymmetric disulfide compound, characterized in that the process comprises starting with a compound having a sulfide structure represented by the general structural formula (II) and having a leaving group,

Wherein S is a sulfur atom, O is an oxygen atom, LG is a leaving group;

r ¹ is selected from methyl, ethyl, isopropyl, phenyl, 4-methylphenyl and

X is selected fromAnd (CH ₂)₂;

The preparation method specifically comprises the following steps:

(S1) oxidizing a compound shown in a structural general formula (II) by an oxidant to obtain a compound containing sulfoxide groups shown in a structural general formula (III);

(S2) in an aqueous solution, reacting a compound shown in a structural general formula (III) with sodium thiosulfate pentahydrate until the conversion is complete, wherein the molar ratio of the compound shown in the structural general formula (III) to the sodium thiosulfate pentahydrate is 0.2-1.0, and then sequentially adding a hydrophobic solvent, R ² SH and alkali or sequentially adding the hydrophobic solvent and R ² SM to obtain an asymmetric disulfide compound containing sulfoxide groups shown in the structural general formula (I);

The reaction scheme is as follows:

Wherein M in R ² SM is an alkali metal element;

R ² in R ² SH and R ² SM is selected from the group consisting of methyl, ethyl, benzyl, 4-methoxybenzyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 2, 3-dimethoxyphenyl, 4-nitrophenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl and 4-bromophenyl.

As a further preferred aspect of the present invention, in the step (S1), the oxidizing agent is m-chloroperoxybenzoic acid (m-CPBA) or Eosin Y (Eosin Y), or a mixture of hydrogen peroxide (H ₂O₂) -acids, wherein when the oxidizing agent is a mixture of hydrogen peroxide (H ₂O₂) -acids, the acid is any one of acetic acid and diphenyl phosphate;

In the step (S2), the alkali is any one of sodium hydroxide, potassium carbonate, sodium carbonate and potassium phosphate, preferably potassium carbonate;

The hydrophobic solvent is any one of dichloromethane, dichloroethane, ethyl acetate, toluene and n-butanol, preferably dichloromethane;

The molar ratio of the compound shown in the structural general formula (III) to R ² SH is 0.2-1.0, the molar ratio of the compound shown in the structural general formula (III) to alkali is 0.5-1.0, or the molar ratio of the compound shown in the structural general formula (III) to R ² SM is 0.2-1.0.

As a further preferred aspect of the present invention, in the structural formula (II), LG is preferably a bromine atom, a chlorine atom or a p-toluenesulfonyl group;

m is preferably sodium or potassium.

According to a further aspect of the present invention there is provided the use of an asymmetric disulphide compound comprising sulphoxide groups as described above as an activating reagent in a glycosylation reaction.

As a further preferred aspect of the invention, the application is in particular that the asymmetric disulfide compound containing sulfoxide groups participates in activating a glycosyl donor to realize the connection between glycosyl units or the connection between glycosyl units and non-glycosyl units.

As a further preferred aspect of the present invention, the present invention is applied specifically, in an organic solvent, a composition of an activating reagent represented by the general structural formula (I) and trifluoromethanesulfonic anhydride is used as an accelerator, and a glycosyl donor represented by the general structural formula (IV) and an acceptor represented by the general formula (V) are subjected to glycosylation reaction to obtain a glycosylation product represented by the general formula (VI), wherein the reaction equation is as follows:

in the glycosyl donor shown in the general formula (IV), gly is glycosyl with hydroxyl and/or amino on the glycosyl ring protected by protecting groups, Z is sulfur or selenium atom, R ³ is selected from substituted or unsubstituted alkyl and substituted or unsubstituted aryl;

The acceptor represented by formula (V) is selected from sugar nucleophiles in which the hydroxyl and/or amino groups on the sugar ring are partially protected by protecting groups, or alcohols, phenols, carboxylic acids, pyrimidines, purines, enol silyl ethers containing one or more nucleophilic groups.

As a further preferred aspect of the present invention, gly or the acceptor represented by formula (V) is a sugar independently selected from any one of D-glucose, D-galactose, D-mannose, L-rhamnose, D-xylose, D-quinolone, D-fucose, L-fucose, 2-deoxy-L-fucose, D-ribose, 6-deoxy-D-ribose, sialic acid, D-furanose, 2-amino-2-deoxy-D-glucose, 3-aminopolydeoxyglucose;

Gly or the acceptor represented by formula (V), wherein the protecting group is independently selected from any one of acetyl (Ac), benzoyl (Bz), benzyl (Bn), tert-butyldimethylsilyl (TBS), benzylidene acetal, carbonate, azocarbonate, propiketal, benzyloxycarbonyl (Cbz), p-Methoxyphenyl (MP), S-2-methylbutanoyl (Mba) and p-nitrobenzenesulfonyl (Ns);

R ³ is selected from substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted 1-adamantyl and substituted or unsubstituted phenyl, wherein one or more substituents are independently selected from methyl, ethyl, methoxy and phenyl;

the organic solvent is one or more of halogenated hydrocarbon solvents, aromatic hydrocarbon solvents and nitrile solvents;

the molar ratio of the asymmetric disulfide compound containing sulfoxide groups and shown in the structural general formula (I) to the glycosyl donor shown in the structural general formula (IV) is 0.5-1.2;

The molar ratio of the trifluoro methanesulfonic anhydride to the glycosyl donor shown in the structural general formula (IV) is 0.5-1.2;

the reaction temperature range of the glycosylation reaction is-78-30 ℃.

As a further preferred aspect of the present invention, the glycosyl donor represented by the general structural formula (IV) is specifically any one of the compounds of structural formulae IV-01 to IV-29:

The acceptor represented by the formula (V) is a sugar nucleophile in which a hydroxyl group and/or an amino group on the sugar ring is partially protected by a protecting group, specifically any one of the compounds of the structural formulae V-01 to V-13:

or the receptor represented by formula (V) is an alcohol nucleophile, specifically any one of the compounds of structural formulas V-14 to V-18:

Or the receptor represented by the formula (V) is a phenol or carboxylic acid nucleophilic reagent, specifically a compound of the structural formula V-19 or the structural formula V-20:

Or the receptor represented by the formula (V) is a pyrimidine or purine nucleophile, specifically any one of the compounds of the structural formulas V-21 to V-24:

or the receptor expressed by the formula (V) is enol silicon ether nucleophilic reagent, specifically a compound of the structural formula V-25:

compared with the prior art, the asymmetric disulfide compound containing sulfoxide groups, which has the structure shown in the structural general formula (I), is reported for the first time through the technical scheme, and the compound shown in the structural general formula (I), the corresponding preparation method and the application of the compound serving as an activating reagent in glycosylation reaction are not reported in published literature. In particular, the invention can achieve the following beneficial effects:

1) The compound shown in the structural general formula (I) has novel structure, stable property, easy storage (can be stably stored in room temperature air atmosphere, and has no obvious reduction of reaction activity) and no pungent smell;

2) The preparation method of the asymmetric disulfide compound containing sulfoxide groups has the advantages of low-cost and easily available raw materials, simple operation, high reaction yield, convenient separation and purification of intermediates and products, and suitability for industrial production. The preparation method can take a compound which is shown in a structural general formula (II) and contains a thioether structure and has a leaving group as an initial raw material, and obtain a target asymmetric disulfide compound product containing sulfoxide groups through two stages (specifically comprising a one-step oxidation reaction and a two-step disulfide construction reaction) of thioether oxidation and asymmetric disulfide bond construction. The reaction scheme is as follows:

The preparation method has the advantages of I) simplicity in operation, insensitivity to water and oxygen, II) low cost, low toxicity, environment friendliness, iii) high synthesis efficiency, the total multi-step synthesis yield of most of examples is more than 70% and up to 87%, iv) convenience in purification, recrystallizability and pulping purification of intermediates shown in a structural general formula (II), extraction and purification after adding sodium thiosulfate pentahydrate to introduce a water-soluble sodium thiosulfate functional group, and extraction and purification of end products shown in a structural general formula (I), partial recrystallizability and pulping purification of end products shown in the structural general formula (I), easiness in column chromatography purification due to large polarity difference between main and byproducts (symmetrical disulfide), and enlargement of the preparation scale, suitability for industrial scale production, and preparation of a hundred gram scale (as exemplified in a later embodiment 41) of a compound I-02, and the synthesis scale of a compound I-09 also reaching the order of 25 g (as exemplified in a later embodiment 10).

In the preparation process, the molar ratio of the compound shown in the structural formula (III) to the sodium thiosulfate pentahydrate is controlled to be 0.2-1.0, and the compound and the sodium thiosulfate pentahydrate react to be completely converted, so that the complete conversion of the structural formula (III) can be ensured on one hand, the subsequent separation of the structural formula (I) is avoided (because the polarity of the structural formula III and the polarity of the structural formula I are not greatly different), and the generation of byproducts can be reduced on the other hand. In addition, the compound shown in the general structural formula (III) is mostly solid, when the synthesis scale is large, recrystallization operation can be adopted, and the intermediate and the product compound shown in the formula (I) are very convenient to separate and purify because of large polarity difference of main and byproduct in the disulfide bond construction stage.

3) The addition of the hydrophobic solvent, R ² SH and alkali to the reaction system is strictly carried out according to the sequence of adding the hydrophobic solvent and R ² SM in turn, or the hydrophobic solvent is used as a protective agent to prevent the alkali from decomposing the compound shown in the structural formula (I) generated in the system and reduce the generation of byproducts, and the operations of adding R ² SH and then adding alkali are carried out in the manner of regulating the pH value in the reaction system and protecting the compound shown in the structural formula (I) generated in the system.

4) The asymmetric disulfide compound containing sulfoxide groups, which is obtained by the invention, can be particularly applied to glycosylation reaction as an activating reagent. The asymmetric disulfide compound containing sulfoxide groups contains disulfide and sulfoxide functional groups, and can generate a high-activity thiophilic intermediate in situ under the action of trifluoromethanesulfonic anhydride, so that the effect equivalent to that of the active intermediate of the triflic anhydride is achieved, and meanwhile, the use of reagents which are commonly used in the preparation of the active intermediate and contain toxic substances, malodors, expensive, unstable or metal is avoided. And the minimum amount of reagent and anhydride can be up to 0.5 equivalent of the glycosyl donor (i.e., 0.5:1 molar ratio of activating reagent to glycosyl donor, 0.5:1 molar ratio of triflic anhydride to glycosyl donor).

5) The asymmetric disulfide compound containing sulfoxide groups has wide application range in glycosylation reaction, is suitable for construction of carbon-oxygen, carbon-nitrogen and carbon-carbon glycosidic bonds, can realize efficient synthesis of oxy-glycoside, phenol-glycoside, ester-glycoside, nucleoside and azoside, is simple and convenient to operate, has short reaction time (can be completed within 5 minutes at maximum), and has good application prospect.

Moreover, the present invention is also applicable to activating some less active glycosyl donors (e.g., disarmed glycosyl donors, etc., as exemplified in example 42, etc., hereinafter), which are not available in other activating reagents of the prior art (as exemplified in comparative example 1, hereinafter).

Detailed Description

The present invention will be described in further detail with reference to the following examples in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention. In addition, the technical features of the embodiments of the present invention described below may be combined with each other as long as they do not collide with each other.

The asymmetric disulfide compounds containing sulfoxide groups, which are shown in the general structural formula (I), can be synthesized according to examples 1-41, and their effect as an activating reagent in glycosylation reactions can be seen in detail in examples 42-72 below. The following are specific examples:

table 1 shows examples of compounds satisfying the structural general formula (I) of the present invention

The asymmetric disulfide compound containing sulfoxide groups, which is shown in the structural general formula (I), can be prepared according to the following method:

The preparation method comprises two stages of thioether oxidation and asymmetric disulfide bond construction, namely, a compound which is shown in a structural general formula (II) and contains a thioether structure and has a leaving group is used as an initial raw material, a sulfoxide functional group is introduced into the compound through oxidation of an oxidant to prepare a compound (III), the compound shown in the structural general formula (III) reacts with sodium thiosulfate pentahydrate in an aqueous solution until the conversion is complete, and then a hydrophobic solvent, R ² SH, alkali or a hydrophobic solvent and R ² SM are sequentially added to react to prepare the compound shown in the structural general formula (I).

The operation steps of the selective oxidation stage are different according to different oxidants, and specifically include the following steps:

Weighing a compound (II) in a reaction bottle, adding dichloromethane (to ensure that the concentration c=0.2M of the compound with the structural formula II) is dissolved, slowly dropwise adding a dichloromethane solution of M-chloroperoxybenzoic acid (M-CPBA, 1.0 equivalent) into the reaction bottle at the temperature of-20 ℃, continuing to react for 0.5 hour at the temperature of-20 ℃ until the reaction is complete after the dropwise adding, adding a saturated sodium thiosulfate aqueous solution to terminate the reaction, diluting a reaction system with ethyl acetate, washing with water, saturated sodium bicarbonate and a saturated sodium chloride solution in sequence, merging organic phases, drying with anhydrous sodium sulfate, filtering and concentrating, and separating by column chromatography or recrystallization operation to obtain the compound (III);

Weighing a compound (II) and Eosin Y (Eosin Y,0.05 equivalent) in a reaction bottle, adding ethanol (the concentration of the compound with the general formula II is c=0.2M) for dissolution, radiating a 5W Blue LED lamp for a certain time until the raw materials are completely reacted, diluting a reaction system by using ethyl acetate, washing the reaction system by using water and saturated sodium chloride solution in sequence, merging organic phases, drying the organic phases by using anhydrous sodium sulfate, filtering and concentrating the organic phases, and separating the organic phases by column chromatography to obtain a compound (III);

And (C) in the oxidation step, weighing the compound (II) and diphenyl phosphate ((PhO) ₂ P (O) OH,0.1 equivalent) in a reaction bottle, adding ethyl acetate for dissolution, adding 30wt% of aqueous hydrogen peroxide solution under ice bath, heating the reaction system to 60 ℃ for reaction for a certain time until the reaction is complete, adding saturated aqueous sodium thiosulfate solution for terminating the reaction, diluting the reaction system with ethyl acetate, washing the reaction system with water, saturated sodium bicarbonate and saturated sodium chloride solution in sequence, merging organic phases, drying the organic phases with anhydrous sodium sulfate, filtering and concentrating the organic phases, and purifying the organic phases through column chromatography or recrystallization operation to obtain the compound (III).

And (D) an oxidation step, namely weighing the compound (II) in a reaction bottle, adding acetic acid (1.0 equivalent), slowly dropwise adding 30wt% of hydrogen peroxide water solution (4.0 equivalent) at room temperature, and keeping the room temperature for reaction until the reaction is complete (the product is gradually separated out as the reaction proceeds). And adding a sufficient amount of water into the reaction system, fully stirring, and carrying out vacuum filtration and freeze-drying to obtain the compound (III).

Example 1 Selective Oxidation of different types of oxidants to introduce sulfoxide functionality (exemplified by the Synthesis of Compound III-03)

After synthesis of II-03 according to literature (Tetrahedron Lett.,2017,58,2381-2384), 2- (2-propylthio) benzyl chloride II-03 was used as starting material and subjected to recrystallization to give white solid III-03 (5.0 g, 94%) by reference to general oxidation step A, 2- (2-propylthio) benzyl chloride II-03 was used as starting material to give white solid III-03 (100 mg, 94%), and 2- (2-propylthio) benzyl chloride II-03 was used as starting material to give white solid III-03(46g,91％).¹H NMR(600MHz,CDCl₃)δ7.86(1H,d,J＝7.2Hz,Ar-H),7.54-7.46(3H,m,Ar-H),4.71(2H,s,-CH₂Ph),3.05-2.99(1H,m,-CH(CH₃)₂),1.31(3H,d,J＝6.6Hz,-CH(CH₃)₂),1.17(3H,d,J＝6.6Hz,-CH(CH₃)₂).¹³C NMR(100MHz,CDCl₃)δ141.7,135.6,131.6,131.1,129.7,126.0,54.3,41.6,17.6,13.3.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₀H₁₃ClOSNa 239.0268;Found 239.0265. by recrystallization with little influence on yield.

Example 2 Selective Oxidation of Hydrogen peroxide-acid mixtures to introduce sulfoxide functionality (exemplified by the Synthesis of Compound III-01)

After synthesis of II-01 according to the literature (J.org.chem., 2011,76,1513-1520), 2-methylthiobenzyl chloride II-01 was used as starting material and a white solid III-01 (14 g, 94%) was obtained by recrystallization operation with reference to the general oxidation step C, and 2-methylthiobenzyl chloride II-01 was used as starting material to obtain a white solid with reference to the general oxidation step D III-01(5g,91％).¹H NMR(600MHz,CDCl₃)δ8.03(1H,dd,J＝7.8,1.2Hz,Ar-H),7.58(1H,td,J＝7.8,1.2Hz,Ar-H),7.48(1H,td,J＝7.2,1.2Hz,Ar-H),7.40(1H,dd,J＝7.2,1.2Hz,Ar-H),4.80(1H,d,J＝11.4Hz,-CH₂Ph),4.61(1H,d,J＝11.4Hz,-CH₂Ph),2.81(3H,s,-CH₃).¹³CNMR(150MHz,CDCl₃)δ145.5,134.3,131.7,130.8,130.7,124.4,44.2,41.8.HRMS(ESI-TOF)m/z:[M+Na]⁺calcd for C₈H₉ClOSNa 210.9955;Found 210.9949.

EXAMPLE 3 Synthesis of Compound III-02

After synthesis of II-02 according to a similar procedure to the synthesis of compound 5C in literature (J.org.chem., 2011,76,1513-1520), reference is made to the general oxidation step C, starting from 2-ethylsulfanylbenzyl chloride II-02, a white solid is obtained by a recrystallisation operation III-02(879mg,92％).¹H NMR(600MHz,CDCl₃)δ7.94(1H,dd,J＝7.8,1.2Hz,Ar-H),7.55(1H,td,J＝7.8,1.2Hz,Ar-H),7.48(1H,td,J＝7.2,1.2Hz,Ar-H),7.43(1H,dd,J＝7.2,1.2Hz,Ar-H),4.76(1H,d,J＝12.0Hz,-CH₂Ph),4.64(1H,d,J＝12.0Hz,-CH₂Ph),3.06-3.00(1H,m,-CH₂CH₃),2.88-2.82(1H,m,-CH₂CH₃),1.29(3H,t,J＝7.8Hz,-CH₂CH₃).¹³C NMR(150MHz,CDCl₃)δ143.1,134.9,131.6,131.0,130.2,125.4,50.6,41.7,6.9.HRMS(ESI-TOF)m/z:[M+Na]⁺calcd for C₉H₁₁ClOSNa 225.0111;Found225.0106.

EXAMPLE 4 Synthesis of Compound III-04

After synthesis of II-04 according to literature (Monatash. Chem.,1965,96,182-207), reference is made to general oxidation step A, starting from 2-phenylsulfanylbenzyl chloride II-04, giving a white solid III-04(0.4g,95％).¹H NMR(600MHz,CDCl₃)δ7.84(1H,m,Ar-H),7.65-7.64(2H,m,Ar-H),7.50-7.48(1H,m,Ar-H),7.47-7.43(5H,m,Ar-H),4.88(1H,d,J＝12.0Hz,-CH₂Ph),4.70(1H,d,J＝12.0Hz,-CH₂Ph).¹³C NMR(150MHz,CDCl₃)δ144.6,144.3,136.1,132.0,131.3,130.9,130.3,129.6,126.5,125.6,41.8.HRMS(ESI-TOF)m/z:[M+Na]⁺calcd for C₁₃H₁₁ClOSNa273.0111;Found 273.0111.

EXAMPLE 5 Synthesis of Compound III-05

After synthesis of II-05 according to the literature (Collet. Czech. Chem. Commun.,1968,33,1895-1910), reference is made to general oxidation step A, starting with 2- (4-methylphenylsulfanyl) benzyl chloride II-05, a white solid is obtained III-05(0.4g,97％).¹H NMR(400MHz,CDCl₃)δ7.90-7.86(1H,m,Ar-H),7.54-7.44(5H,m,Ar-H),7.25(2H,d,J＝6.8Hz,Ar-H),4.83(1H,d,J＝12.0Hz,-CH₂Ph),4.67(1H,d,J＝12.0Hz,-CH₂Ph),2.35(s,3H,-CH₃).¹³C NMR(150MHz,CDCl₃)δ144.4,142.0,141.4,135.8,131.9,130.8,130.3,126.2,125.8,41.9,21.6.HRMS(ESI-TOF)m/z:[M+Na]⁺calcd for C₁₄H₁₃ClOSNa 287.0268;Found 287.0261.

EXAMPLE 6 Synthesis of Compound III-06

After S1 was synthesized according to the literature (J.am.chem.Soc.2020, 142, 5498-5503), S1 (34 mg,0.16 mmol) and 4-dimethylaminopyridine (4 mg,0.03 mmol) were weighed into a reaction flask, dissolved in methylene chloride (0.8 mL) and triethylamine (45. Mu.L, 0.32 mmol) and p-toluenesulfonyl chloride (62 mg,0.32 mmol) were added sequentially under ice bath. After the addition was completed, the reaction mixture was allowed to react at room temperature for 24 hours. After the reaction was completed, the reaction system was diluted with ethyl acetate, and washed with water, saturated sodium bicarbonate, and saturated sodium chloride solution in this order. Then the organic phase is dried by anhydrous sodium sulfate, filtered and concentrated, and the crude product is purified by silica gel column chromatography to obtain oily liquid II-06(29mg,78％).¹H NMR(400MHz,CDCl₃)δ7.34(1H,dd,J＝7.6,1.2Hz,Ar-H),7.21(1H,t,J＝7.6Hz,Ar-H),7.12(1H,d,J＝7.6Hz,Ar-H),4.96(2H,s,-CH₂Ph),3.41(1H,hept,J＝6.8Hz,-CH(CH₃)₂),2.79(2H,q,J＝7.6Hz,-CH₂CH₃),1.29(6H,d,J＝7.2Hz,-CH(CH₃)₂),1.27(3H,t,J＝7.2Hz,-CH₂CH₃).¹³C NMR(150MHz,CDCl₃)δ144.4,139.2,133.7,129.5,127.8,127.1,41.7,40.3,29.9,25.9,22.6,15.6.HRMS(ESI-TOF)m/z:[M+O+Na]⁺calc.for C₁₂H₁₇OClSNa 267.0581;Found267.0582.

Referring to general oxidation step A, starting with 2- (2-propylsulfanyl) -6-ethylbenzyl chloride II-06, a colorless liquid is obtained III-06(30mg,92％).¹H NMR(400MHz,CDCl₃)δ7.72(1H,d,J＝8.0Hz,Ar-H),7.49(1H,t,J＝8.0Hz,Ar-H),7.37(1H,d,J＝7.6Hz,Ar-H),4.80(1H,d,J＝12.0Hz,-CH₂Ph),4.76(1H,d,J＝12.0Hz,-CH₂Ph),3.08(1H,hept,J＝6.8Hz,-CH(CH₃)₂),2.82(2H,q,J＝7.6Hz,-CH₂CH₃),1.35(3H,d,J＝7.2Hz,-CH(CH₃)₂),1.29(3H,t,J＝7.6Hz,-CH₂CH₃),1.14(3H,d,J＝6.4Hz,-CH(CH₃)₂).¹³C NMR(150MHz,CDCl₃)δ145.1,142.7,132.7,131.8,129.9,123.8,54.0,38.3,25.0,18.0,15.4,13.0.HRMS(ESI-TOF)m/z:[M+Na]⁺calcd for C₁₂H₁₇ClOSNa 267.0581;Found 267.0584.

EXAMPLE 7 Synthesis of Compound III-07

Compound II-07 (170mg,3%for 4steps) was synthesized starting from commercially available material S2 according to a similar procedure to that described in the literature (Monatsh. Chem.1965,96, 182-207) for the synthesis of compound XXXV. R _f =0.53 (petroleum ether) ).¹HNMR(400MHz,CDCl₃)δ7.99(1H,s,Ar-H),7.87(1H,s,Ar-H),7.84-7.82(1H,m,Ar-H),7.71-7.69(1H,m,Ar-H),7.51-7.45(2H,m,Ar-H),7.30-7.19(5H,m,Ar-H),4.88(2H,s,-CH₂).¹³C NMR(150MHz,CDCl₃)δ136.3,136.1,134.1,133.8,133.0,131.7,130.0,130.0,129.5,128.0,127.5,127.3,127.2,127.0,45.2.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₇H₁₃ClOSNa 323.0268;Found 323.0274.

Referring to the general oxidation step A, 2-phenylthio-3-chloromethylnaphthalene II-07 is taken as a starting material to obtain III-07(136mg,77％).¹H NMR(400MHz,CDCl₃)δ8.49(1H,s,Ar-H),7.97(1H,m,Ar-H),7.93(1H,s,Ar-H),7.87-7.85(1H,m,Ar-H),7.68-7.65(2H,m,Ar-H),7.61-7.56(2H,m,Ar-H),7.44(3H,m,Ar-H),4.82(1H,d,J＝12.4Hz,-CH₂),4.71(1H,d,J＝12.0Hz,-CH₂).¹³C NMR(150MHz,CDCl₃)δ144.5,141.0,134.5,133.0,131.9,131.7,130.8,129.7,128.9,128.7,128.1,128.0,127.6,126.5,42.5.HRMS(ESI-TOF)m/z:[M+Na]⁺calcd for C₁₇H₁₃ClOSNa323.0268;found 323.0277.

EXAMPLE 8 Synthesis of Compound III-08

After synthesis of S3 according to literature (chem. Sci.,2022,13,8759-8765), S3 (150 mg,0.16 mmol) was weighed into a reaction flask, dissolved in dichloromethane (0.4 mL) and a dichloromethane solution of thionyl chloride (18 μl,0.25 mmol) was slowly added dropwise under ice bath, after the addition was completed, the reaction was allowed to proceed to room temperature for 0.5 hours. After the reaction was completed, the reaction system was diluted with ethyl acetate, and washed with water, saturated sodium bicarbonate, and saturated sodium chloride solution in this order. The organic phase is dried by anhydrous sodium sulfate, filtered and concentrated, and the crude product is purified by silica gel column chromatography to obtain the compound II-08(98 mg,64％).H NMR(600 MHz,CDCl₃)δ7.53-7.51(1H,m,Ar-H),7.46-7.45(1H,m,Ar-H),7.29-7.27(2H,m,Ar-H),4.84(2H,s,-CH₂Ph),3.71(4H,t,J＝6.6 Hz),3.69-3.64(4H,m),3.38-3.35(1H,m,SCH),2.40-2.32(4H,m,-CH₂CH₂C₆F₁₃).¹³C NMR(150 MHz,CDCl₃)δ139.9,134.5,134.1,130.8,129.4,128.6,70.4,63.3(t,J＝4.0 Hz,-CH₂CH₂C₆F₁₃),49.1,44.8,31.5(t,J＝21.6 Hz,-CH₂CH₂C₆F₁₃).HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₂₆H₁₉ClF₂₆O₂SNa 947.0271;Found 947.0276.

Referring to general oxidation step A, starting with 2- (2-propylsulfanyl) -6-ethylbenzyl chloride II-08, a colorless liquid is obtained III-08(100 mg,85％).¹H NMR(600 MHz,CDCl₃)δ7.90-7.89(1H,m,Ar-H),7.55-7.49(3H,m,Ar-H),4.76(1H,d,J＝12.0 Hz,-CH₂Ph),4.67(1H,d,J＝12.0 Hz,-CH₂Ph),3.79-3.68(6H,m),3.64-3.57(2H,m),3.31-3.27(1H,m),2.39-2.30(2H,m),2.26-2.19(2H,m).¹³C NMR(150 MHz,CDCl₃)δ141.1,135.8,131.9,131.3,129.8,125.7,66.8,64.3,63.9,63.5,63.2,41.2,31.5(t,J＝21.5 Hz,-CH₂CH₂C₆F₁₃),31.4(t,J＝21.6 Hz,-CH₂CH₂C₆F₁₃).HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₂₆H₁₉ClF₂₆O₃SNa 963.0220;Found 963.0209.

EXAMPLE 9 Synthesis of Compound III-09

After synthesis of II-09 following a procedure analogous to that for synthesis of compound 10 in literature (Synthesis., 2011,3,397-408), reference is made to general oxidation step A, starting with 3-chloropropylphenyl sulfide II-09, to yield colorless liquid III-09 (40 mg, 85%). The obtained product was immediately subjected to a nuclear magnetic test, and the results were as follows ：¹H NMR(600 MHz,CD₂Cl₂)δ7.74-7.73(2H,m,Ar-H),7.56-7.51(5H,m,Ar-H),7.37-7.35(2H,d,J＝8.0 Hz,Ar-H),4.12-4.08(1H,m),4.07-4.03(1H,m),2.88-2.84(1H,m),2.70-2.66(1H,m),2.44(3H,s,-CH₃),2.13-2.06(1H,m),1.91-1.84(1H,m).¹³C NMR(150 MHz,CD₂Cl₂)δ145.6,144.0,133.0,131.3,130.3,129.6,128.2,124.2,69.4,52.9,22.0,21.7.HRMS(ESI-TOF)m/z:[M+H]⁺Calcd for C₁₆H₁₉O₄S₂ 339.0719;Found 339.0715.

Specific optimization data of the types of hydrophobic solvents and bases in the construction stage of the asymmetric disulfide of the compound shown in the formula (I) are shown in examples 10-11:

Example 10 screening of hydrophobic solvent species (exemplified by the Synthesis of Compound I-09)

Weighing a compound III-03 and sodium thiosulfate pentahydrate in a reaction bottle, adding a proper amount of water (the concentration C of sodium thiosulfate pentahydrate is 0.4M), heating to 50 ℃ for reaction for 4 hours, clarifying the reaction system, cooling the reaction system to 0 ℃ without any post-treatment operation after TLC monitoring that the conversion of the compound III-03 is complete, sequentially adding an aqueous solution of a hydrophobic solvent (v _{Hydrophobic solvent}/v_{water in the system} =1:6, the volume ratio is the same as below), sodium thiophenoxide (1.2 equivalent, the concentration c=1M) for reaction for 6 hours at 0 ℃, diluting with methylene chloride, washing with water for three times, merging organic phases, drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by column chromatography to obtain colorless oily liquid I-09. Wherein, the reaction efficiency of different kinds of hydrophobic solvents is different, the effect is the best when methylene dichloride is used as the hydrophobic solvent (1.34g,90%for 2steps. In addition, based on the reaction conditions, the expansion reaction is carried out, the yield of I-09 with 25g scale can be obtained with 84% of two steps, the yield is slightly reduced ).¹H NMR(400MHz,CDCl₃)δ7.83-7.80(1H,dd,J＝8.0,2.0Hz,Ar-H),7.46-7.42(3H,m,Ar-H),7.37(1H,td,J＝7.2,1.2Hz,Ar-H),7.33-7.27(3H,m,Ar-H),7.21(1H,m,Ar-H),4.09(1H,d,J＝12.8Hz,-CH₂Ph),4.03(1H,d,J＝12.8Hz,-CH₂Ph),2.91(1H,hept,J＝7.2Hz,-CH(CH₃)₂),1.22(3H,d,J＝7.2Hz,-CH₃),1.10(3H,d,J＝7.2Hz,-CH₃).¹³C NMR(100MHz,CDCl₃)δ141.6,136.6,134.5,131.4,131.1,129.3,128.8,128.6,127.6,125.9,54.2,39.2,17.6,13.2.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₆H₁₈OS₃Na 345.0412;Found 345.0411., and methylene dichloride is used as the hydrophobic solvent in the subsequent examples unless specified.

EXAMPLE 11 selection of the base species (exemplified by the Synthesis of Compound I-02)

Weighing a compound III-01 and sodium thiosulfate pentahydrate in a reaction bottle, adding a proper amount of water (the concentration c=0.4M of sodium thiosulfate pentahydrate), heating to 50 ℃ for reaction for 4 hours, clarifying a reaction system, cooling the reaction system to 0 ℃ without any post-treatment operation after TLC monitoring that the conversion of the compound III-01 is complete, sequentially adding a hydrophobic solvent dichloromethane (v _{Dichloromethane (dichloromethane)}/v_{water in the system} =1:6), 4-methyl thiophenol (1.2 equivalent) and alkali (1.0 equivalent, the concentration c=0.8M) aqueous solution for reaction for 2.5 hours, diluting with dichloromethane, washing with water for three times, merging organic phases, drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by recrystallization operation to obtain white solid I-02. Wherein, when potassium carbonate is used as alkali, the reaction effect is best (1.5g,92％for 2steps).¹H NMR(600MHz,CDCl₃)δ7.98(1H,dd,J＝7.8,0.6Hz,Ar-H),7.51(1H,td,J＝7.8,0.6Hz,Ar-H),7.41(1H,td,J＝7.8,1.2Hz,Ar-H),7.30(2H,d,J＝8.4Hz,Ar-H),7.26(1H,d,J＝7.8Hz,Ar-H),7.09(2H,d,J＝8.4Hz,Ar-H),4.13(1H,d,J＝13.2Hz,-CH₂Ph),4.00(1H,d,J＝13.2Hz,-CH₂Ph),2.68(3H,s,-CH₃),2.32(3H,s,-CH₃).¹³C NMR(150MHz,CDCl₃)δ145.3,138.3,133.9,133.0,131.4,131.2,130.1,129.9,129.7,124.4,44.0,39.1,21.3.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₅H₁₆OS₃Na 331.0255;Found 331.0257.. In the following examples, if no special description exists, the potassium carbonate is used as alkali.

Examples 12 to 40 asymmetric disulfide construction stage of the Compound of the general structural formula (I) according to the present invention

The asymmetric disulfide build stages of examples 12-40, unless otherwise specified, can be performed according to the following two standard set of procedures:

And a disulfide construction step D, namely weighing the compound (III) and sodium thiosulfate pentahydrate (1.3 equivalent) in a reaction bottle, adding a proper amount of water (the concentration c=0.4M corresponding to the sodium thiosulfate pentahydrate), suspending the compound (III) in the water, heating to 50 ℃ for reaction for a period of time, clarifying the reaction system without insoluble substances, cooling the reaction system to 0 ℃ without any post-treatment operation after the complete conversion of the compound (III) is monitored by TLC, sequentially adding an aqueous solution (the concentration c=1M of methylene dichloride (v _{Dichloromethane (dichloromethane)}/v_{water in the system}＝1:6)、R² SM) (1.2 equivalent)) for reaction for a period of time, diluting with methylene dichloride, washing with water for three times, combining organic phases, drying with anhydrous sodium sulfate, filtering and concentrating, and purifying by column chromatography or recrystallization operation to obtain the asymmetric disulfide compound (I) containing sulfoxide groups.

And (E) weighing the compound (III) and sodium thiosulfate pentahydrate (1.3 equivalent) in a reaction bottle, adding a proper amount of water (the concentration c=0.4M corresponding to sodium thiosulfate pentahydrate), suspending the visible compound (III) in the water, heating to 50 ℃ for reaction for a period of time, clarifying the reaction system without insoluble substances, cooling the reaction system to 0 ℃ without any post-treatment operation after TLC monitoring the complete conversion of the compound (III), sequentially adding dichloromethane (v _{Dichloromethane (dichloromethane)}/v_{water in the system}＝1:6)、R² SH (1.2 equivalent) and potassium carbonate (1.0 equivalent) for reaction for a certain period of time, diluting with dichloromethane, washing with water for three times, combining organic phases, drying with anhydrous sodium sulfate, filtering, concentrating, and purifying by column chromatography or recrystallization operation to obtain the asymmetric disulfide compound (I) containing sulfoxide groups.

EXAMPLE 12 Synthesis of Compound I-01

Referring to general disulfide construction step D, starting with compound III-01 (wherein R ² SM is sodium thiophenol), a white solid is obtained I-01(1.4g,90％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.97(1H,dd,J＝8.0,1.2Hz,Ar-H),7.50(1H,td,J＝7.6,1.2Hz,Ar-H),7.42-7.38(3H,m,Ar-H),7.30-7.20(4H,m,Ar-H),4.14(1H,d,J＝12.8Hz,-CH₂Ph),4.00(1H,d,J＝12.8Hz,-CH₂Ph),2.69(1H,s,-CH₃).¹³C NMR(150MHz,CDCl₃)δ145.2,136.5,133.8,131.4,131.3,129.7,129.3,129.0,127.8,124.4,44.0,39.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₄H₁₄OS₃Na317.0099;Found 317.0100.

EXAMPLE 13 Synthesis of Compound I-03

Referring to general disulfide construction step E, starting with compound III-01 (wherein R ² SH is 4-methoxyphenylthiophenol), a colourless oily liquid is obtained Ⅰ-03(1.6g,93％for 2steps).¹H NMR(600MHz,CDCl₃)δ7.97(1H,dd,J＝7.8,1.2Hz,Ar-H),7.51(1H,td,J＝7.8,1.2Hz,Ar-H),7.42(1H,td,J＝7.8,1.2Hz,Ar-H),7.34-7.31(2H,m,Ar-H),7.27(1H,dd,J＝7.8,0.8Hz,Ar-H),6.82-6.79(2H,m,Ar-H),4.13(1H,d,J＝12.6Hz,-CH₂Ph),4.01(1H,d,J＝12.6Hz,-CH₂Ph),3.79(3H,s,-OCH₃),2.64(3H,s,-CH₃).¹³C NMR(150MHz,CDCl₃)δ160.3,145.3,134.0,133.2,131.4,131.2,129.7,127.3,124.4,114.9,55.7,43.9,39.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₅H₁₆O₂S₃Na 347.0205;Found 347.0207.

EXAMPLE 14 Synthesis of Compound I-04

Referring to general disulfide construction step E, starting with compound III-01 (wherein R ² SH is 4-bromophenylthiophenol), a white solid is obtained Ⅰ-04(200mg,58％for 2steps).¹H NMR(600MHz,CDCl₃)δ7.98(1H,dd,J＝7.8,1.2Hz,Ar-H),7.51(1H,td,J＝7.2,1.2Hz,Ar-H),7.40-7.38(3H,m,Ar-H),7.27-7.23(3H,m,Ar-H),4.12(1H,d,J＝13.2Hz,-CH₂Ph),4.00(1H,d,J＝13.2Hz,-CH₂Ph),2.72(3H,s,-CH₃).¹³C NMR(150MHz,CDCl₃)δ145.3,135.8,133.7,132.3,131.3,130.2,129.8,124.5,121.7,44.0,39.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₄H₁₃BrOS₃Na 394.9204;Found 394.9207.

EXAMPLE 15 Synthesis of Compound I-05

Referring to general disulfide construction step E, starting with compound III-01 (wherein R ² SH is 4-nitrophenylsulfol), a pale yellow solid is obtained Ⅰ-05(150mg,49％for 2steps).¹H NMR(400MHz,CDCl₃)δ8.13-8.07(2H,m,Ar-H),7.97(1H,d,J＝7.2Hz,Ar-H),7.54-7.45(3H,m,Ar-H),7.36(1H,td,J＝7.6,1.2Hz,Ar-H),7.23(1H,d,J＝7.6Hz,Ar-H),4.15(1H,d,J＝12.8Hz,-CH₂Ph),4.05(1H,d,J＝13.2Hz,-CH₂Ph),2.78(3H,s,-CH₃).¹³C NMR(100MHz,CDCl₃)δ146.6,145.8,145.2,133.4,131.5,131.3,130.1,126.5,124.6,124.3,43.9,39.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₄H₁₃NO₃S₃Na 361.9950;Found 361.9949.

EXAMPLE 16 Synthesis of Compound I-06

Referring to general disulfide construction step D, starting with compound III-01 (wherein R ² SM is sodium methyl mercaptide), a colourless oily liquid is obtained Ⅰ-06(400mg,75％for 2steps).¹H NMR(400MHz,CDCl₃)δ8.02(1H,dd,J＝8.0,1.2Hz,Ar-H),7.54(1H,td,J＝7.8,1.2Hz,Ar-H),7.45(1H,td,J＝7.8,1.2Hz,Ar-H),7.35(1H,dd,J＝7.8,0.8Hz,Ar-H),4.11(1H,d,J＝13.2Hz,-CH₂Ph),3.96(1H,d,J＝12.8Hz,-CH₂Ph),2.82(3H,s,-CH₃),2.17(3H,s,-CH₃).¹³C NMR(100MHz,CDCl₃)δ145.2,134.7,131.3,131.1,129.6,124.4,44.1,38.5,23.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₉H₁₂OS₃Na 254.9942;Found 254.9941.

EXAMPLE 17 Synthesis of Compound I-07

Referring to general disulfide construction step D, starting with compound III-02 (wherein R ² SM is sodium thiophenol), a pale yellow oily liquid is obtained Ⅰ-07(690mg,91％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.89(1H,d,J＝7.6Hz,Ar-H),7.48-7.36(4H,m,Ar-H),7.30-7.20(4H,m,Ar-H),4.10(1H,d,J＝12.4Hz,-CH₂Ph),4.02(1H,d,J＝12.4Hz,-CH₂Ph),2.89(1H,m,-CH₂),2.75(1H,m,-CH₂),1.23(3H,t,J＝7.6Hz,-CH₃).¹³C NMR(150MHz,CDCl₃)δ143.0,136.5,134.1,131.5,131.2,129.3,129.2,128.8,127.7,125.3,50.5,39.1,7.0.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₅H₁₆OS₃Na 331.0255;Found 331.0254.

EXAMPLE 18 Synthesis of Compound I-08

Referring to general disulfide construction step E, starting with compound III-02 (wherein R ² SH is 4-methoxyphenylthiophenol), a colourless oily liquid is obtained Ⅰ-08(1.5g,90％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.89(1H,dd,J＝7.6,1.2Hz,Ar-H),7.47(1H,td,J＝7.6,1.2Hz,Ar-H),7.40(1H,td,J＝7.6,1.2Hz,Ar-H),7.39-7.33(2H,m,Ar-H),7.29(1H,dd,J＝7.6,1.2Hz,Ar-H),6.83-6.79(m,2H,Ar-H),4.09(1H,d,J＝12.6Hz,-CH₂Ph),4.03(1H,d,J＝12.6Hz,-CH₂Ph),3.79(3H,s,-OMe),2.90-2.77(1H,m,-CH₂),2.75-2.64(1H,m,-CH₂),1.19(3H,t,J＝7.2Hz,-CH₃).¹³CNMR 160.2,143.0,134.2,133.0,131.5,131.1,129.1,127.4,125.3,114.9,55.7,50.4,39.1,7.0.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₆H₁₈O₂S₃Na 361.0361;Found 361.0362.

EXAMPLE 19 Synthesis of Compound I-10

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is 4-methylphenylsulfnol), a pale yellow oily liquid is obtained Ⅰ-10(1.43g,92％for 2steps).¹H NMR(600MHz,CD₂Cl₂)δ7.79(1H,d,J＝7.8Hz,Ar-H),7.47(1H,t,J＝7.8Hz,Ar-H),7.41(1H,t,J＝7.8Hz,Ar-H),7.36(3H,d,J＝7.8Hz,Ar-H),7.14(2H,d,J＝7.8Hz,Ar-H),4.13(1H,d,J＝12.6Hz,-CH₂Ph),4.03(1H,d,J＝12.6Hz,-CH₂Ph),2.87(1H,hept,J＝6.6Hz,-CH(CH₃)₂),2.33(3H,s,-CH₃),1.20(3H,d,J＝7.2Hz,-CH₃),1.06(3H,d,J＝6.6Hz,-CH₃).¹³C NMR(150MHz,CDCl₃)δ141.6,138.0,134.5,133.2,131.4,131.1,130.1,129.6,128.7,125.9,54.0,39.1,21.3,17.6,13.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₇H₂₀S₃Na 359.0568;Found 359.0573.

EXAMPLE 20 Synthesis of Compound I-11

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is 4-methoxyphenylthiophenol), a colourless oily liquid is obtained Ⅰ-11(1.43g,88％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.81(1H,dd,J＝7.6,1.2Hz,Ar-H),7.44(1H,td,J＝7.2,1.2,Hz,Ar-H),7.41-7.36(3H,m,Ar-H),7.32(1H,dd,J＝7.6,1.2Hz,Ar-H),6.84-6.79(2H,m,Ar-H),4.09(1H,d,J＝12.8Hz,-CH₂Ph),4.01(1H,d,J＝12.8Hz,-CH₂Ph),3.79(3H,s,-OCH₃),2.87(1H,hept,J＝6.8Hz,-CH(CH₃)₂),1.19(3H,d,J＝7.2Hz,-CH₃),1.06(3H,d,J＝7.2Hz,-CH₃).¹³C NMR(150MHz,CDCl₃)δ160.1,141.6,134.6,132.8,131.4,131.0,128.7,127.4,125.9,114.9,55.6,54.0,39.1,17.6,13.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₇H₂₀O₂S₃Na 375.0518;Found 375.0522.

EXAMPLE 21 Synthesis of Compound I-12

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is 2-methoxyphenylthiophenol), a colourless oily liquid is obtained Ⅰ-12(1.5g,92％for 2steps).¹H NMR(600MHz,CDCl₃)δ7.84(1H,d,J＝7.2Hz,Ar-H),7.59(1H,dd,J＝7.2,1.2Hz,Ar-H),7.48-7.44(1H,m,Ar-H),7.42-7.38(2H,m,Ar-H),7.25-7.23(1H,m,Ar-H),6.96(1H,td,J＝7.2,1.2Hz,Ar-H),6.88(1H,dd,J＝7.8,0.6Hz,Ar-H),4.13(1H,d,J＝13.2Hz,-CH₂Ph),4.09(1H,d,J＝13.2Hz,-CH₂Ph),3.90(3H,s,-OCH₃),2.97(1H,hept,J＝7.2Hz,-CH(CH₃)₂),1.26(3H,d,J＝7.2Hz,-CH₃),1.12(3H,d,J＝7.2Hz,-CH₃).¹³C NMR(150MHz,CDCl₃)δ157.4,141.6,134.6,131.4,131.1,129.6,129.0,128.7,125.9,124.5,121.5,111.2,56.1,54.1,39.2,17.7,13.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₇H₂₀O₂S₃Na 375.0518;Found 375.0519.

EXAMPLE 22 Synthesis of Compound I-13

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is 3-methoxyphenylthiophenol), a pale yellow oily liquid is obtained Ⅰ-13(1.5g,92％for 2steps).¹H NMR(600MHz,CDCl₃)δ7.82(1H,dd,J＝7.8,1.2Hz,Ar-H),7.44(1H,td,J＝7.8,1.2Hz,Ar-H),7.37(1H,td,J＝7.8,1.8Hz,Ar-H),7.32(1H,dd,J＝7.8,1.2Hz,Ar-H),7.19(1H,t,J＝7.8Hz,Ar-H),7.03-7.02(2H,m,Ar-H),6.75(1H,ddd,J＝7.8,2.4,0.6,Hz,Ar-H),4.19(1H,d,J＝13.2Hz,-CH₂Ph),4.02(1H,d,J＝13.2Hz,-CH₂Ph),3.79(3H,s,-OCH₃),2.91(1H,hept,J＝7.2Hz,-CH(CH₃)₂),1.23(3H,d,J＝6.6Hz,-CH₃),1.11(3H,d,J＝7.2Hz,-CH₃).¹³C NMR(150MHz,CDCl₃)δ160.3,141.6,137.9,134.5,131.4,131.1,130.1,128.8,125.9,120.4,113.5,113.4,55.6,54.2,39.3,17.5,13.3.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₇H₂₀O₂S₃Na 375.0518;Found 375.0520.

EXAMPLE 23 Synthesis of Compound I-14

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is 3, 4-dimethoxythiophenol), a pale yellow oily liquid is obtained Ⅰ-14(785mg,88％for 2steps).¹H NMR(600MHz,CDCl₃)δ7.81(1H,dd,J＝8.4,1.2Hz,Ar-H),7.43(1H,td,J＝7.8,1.2Hz,Ar-H),7.37(1H,td,J＝7.8,1.2,Hz,Ar-H),7.32(1H,dd,J＝7.8,1.2Hz,Ar-H),7.02(1H,dd,J＝7.8,1.8Hz,Ar-H),6.99(1H,d,J＝2.4Hz,Ar-H),6.76(1H,d,J＝8.4Hz,Ar-H),4.12(1H,d,J＝13.2Hz,-CH₂Ph),4.00(1H,d,J＝12.6Hz,-CH₂Ph),3.85(6H,s,-OMe),2.86(1H,hept,J＝6.6Hz,-CH(CH₃)₂),1.18(3H,d,J＝7.2Hz,-CH₃),1.08(3H,d,J＝7.2Hz,-CH₃).¹³C NMR(150MHz,CDCl₃)δ149.6,149.5,141.7,134.7,131.4,131.1,128.7,127.7,125.8,123.7,113.9,111.6,56.3,54.1,39.2,17.5,13.3.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₈H₂₂O₃S₃Na 405.0623;Found 405.0614.

EXAMPLE 24 Synthesis of Compound I-15

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is 4-nitrophenylsulfol), a yellow oily liquid is obtained Ⅰ-15(440mg,52％for 2steps).¹H NMR(600MHz,CDCl₃)δ8.09-8.06(2H,m,Ar-H),7.80(1H,dd,J＝7.8,0.6Hz,Ar-H),7.52-7.49(2H,m,Ar-H),7.44-7.39(1H,td,J＝7.2,1.2Hz,Ar-H),7.32(1H,td,J＝7.8,1.2Hz,Ar-H),7.28(1H,dd,J＝7.8,1.2Hz,Ar-H),4.17(1H,d,J＝13.2Hz,-CH₂Ph),4.03(1H,d,J＝13.2Hz,-CH₂Ph),2.93(1H,hept,J＝6.6Hz,-CH(CH₃)₂),1.22(1H,d,J＝6.6Hz,-CH(CH₃)₂),1.19(1H,d,J＝6.6Hz,-CH(CH₃)₂).¹³C NMR(150MHz,CDCl₃)δ146.5,146.0,134.4,131.3,129.2,126.5,126.1,124.2,54.8,39.3,17.2,14.0.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₆H₁₇NO₃S₃Na 390.0263;Found 390.0263.

EXAMPLE 25 Synthesis of Compound I-16

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is 4-trifluoromethylphenyl thiol), a compound is obtained Ⅰ-16(766mg,85％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.80(1H,dd,J＝8.0,1.2Hz,Ar-H),7.52-7.47(4H,m,Ar-H),7.42(1H,td,J＝7.6,1.2Hz,Ar-H),7.33(1H,td,J＝7.6,1.2Hz,Ar-H),7.28(1H,dd,J＝8.0,1.2Hz,Ar-H),4.12(1H,d,J＝12.8Hz,-CH₂Ph),4.01(1H,d,J＝12.8Hz,-CH₂Ph),2.91(1H,hept,J＝6.8Hz,-CH(CH₃)₂),1.22(3H,d,J＝6.8Hz,-CH₃),1.15(3H,d,J＝6.8Hz,-CH₃).¹³C NMR(150MHz,CDCl₃)δ141.6,134.4,131.3,131.2,129.2(q,J＝32.5Hz),129.0,127.2,126.0(q,J＝3.4Hz),126.0,124.1(q,J＝270.0Hz),54.5,39.2,17.3,13.7.¹⁹F NMR(565MHz,CDCl₃)δ-62.54(br H).HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₇H₁₇F₃OS₃Na 413.0286;Found 413.0278.

EXAMPLE 26 Synthesis of Compound I-17

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is 4-fluorobenzenesulfide), a pale yellow oily liquid is obtained Ⅰ-17(644mg,82％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.81(1H,dd,J＝7.6,1.2Hz,Ar-H),7.43(1H,td,J＝7.6,1.2Hz,Ar-H),7.41-7.37(2H,m,Ar-H),7.35(1H,dd,J＝7.6,1.2Hz,Ar-H),7.30(1H,dd,J＝7.6,1.2Hz,Ar-H),6.99-6.93(2H,m,Ar-H),4.10(1H,d,J＝12.8Hz,-CH₂Ph),4.00(1H,d,J＝12.8Hz,-CH₂Ph),2.88(1H,hept,J＝7.2Hz,-CH(CH₃)₂),1.20(3H,d,J＝6.8Hz,-CH₃),1.10(3H,d,J＝6.8Hz,-CH₃).¹³CNMR(100MHz,CDCl₃)δ162.6(d,J＝248.0Hz),141.6,134.5,131.94(d,J＝3.2Hz),131.5(d,J＝8.3Hz),131.4,131.1,128.8,125.9,116.4(d,J＝22.2Hz),54.2,39.1,17.5,13.4.¹⁹F NMR(565MHz,CDCl₃)δ-113.77(m)HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₆H₁₇FOS₃Na 363.0318;Found 363.0316.

EXAMPLE 27 Synthesis of Compound I-18

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is 4-chlorophenylthiol), a pale yellow oily liquid is obtained Ⅰ-18(540mg,82％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.81(1H,dd,J＝7.6,1.2Hz,Ar-H),7.44(1H,td,J＝7.6,1.2Hz,Ar-H),7.38-7.32(3H,m,Ar-H),7.29(1H,dd,J＝7.6,1.2Hz,Ar-H),7.25-7.21(2H,m,Ar-H),4.09(1H,d,J＝12.8Hz,-CH₂Ph),3.99(1H,d,J＝12.8Hz,-CH₂Ph),2.89(1H,hept,J＝6.8Hz,-CH(CH₃)₂),1.21(3H,d,J＝6.8Hz,-CH₃),1.12(3H,d,J＝6.8Hz,-CH₃).¹³C NMR(100MHz,CDCl₃)δ141.6,135.2,134.4,133.6,131.3,131.1,129.8,129.3,128.9,125.9,54.3,39.1,17.4,13.5.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₆H₁₇ClOS₃Na 379.0022;Found 379.0018.

EXAMPLE 28 Synthesis of Compound I-19

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is 4-bromophenylthiophenol), a yellow oily liquid is obtained Ⅰ-19(580mg,63％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.81(1H,dd,J＝8.0,1.2Hz,Ar-H),7.44(1H,td,J＝7.6,1.2Hz,Ar-H),7.40-7.33(3H,m,Ar-H),7.31-7.26(3H,m,Ar-H),4.09(1H,d,J＝12.8Hz,-CH₂Ph),3.99(1H,d,J＝12.8Hz,-CH₂Ph),2.89(1H,hept,J＝6.8Hz,-CH(CH₃)₂),1.21(3H,d,J＝6.8Hz,-CH₃),1.12(3H,d,J＝6.8Hz,-CH₃).¹³C NMR(150MHz,CDCl₃)δ141.7,135.9,134.4,132.3,131.4,131.1,130.0,128.9,126.0,121.5,54.3,39.1,17.4,13.5.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₆H₁₇BrOS₃Na 422.9517;Found 422.9520.

EXAMPLE 29 Synthesis of Compound I-20

Referring to general disulfide construction step D, starting with compound III-03 (wherein R ² SM is sodium methyl mercaptide), a pale yellow oily liquid is obtained Ⅰ-20(1.0g,83％for 2steps).¹H NMR(600MHz,CDCl₃)δ7.86(1H,dd,J＝7.8,1.2Hz,Ar-H),7.48(1H,td,J＝7.2,1.2Hz,Ar-H),7.44(1H,td,J＝7.2,1.2Hz,Ar-H),7.40(1H,dd,J＝7.8,1.8Hz,Ar-H),4.08(1H,d,J＝13.2Hz,-CH₂Ph),3.97(1H,d,J＝12.6Hz,-CH₂Ph),3.02(1H,hept,J＝6.6Hz,-CH(CH₃)₂),2.19(3H,s,-CH₃),1.29(3H,d,J＝6.6Hz,-CH₃),1.16(3H,d,J＝6.6Hz,-CH₃).¹³C NMR(150MHz,CDCl₃)δ141.4,135.3,131.0,130.9,128.5,125.7,54.0,38.2,23.1,17.3,13.2.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₁H₁₆OS₃Na 283.0255;Found 283.0257.

EXAMPLE 30 Synthesis of Compound I-21

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is ethanethiol), a pale yellow oily liquid is obtained Ⅰ-21(538mg,85％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.86(1H,dd,J＝7.6,1.6,Hz,Ar-H),7.51-7.38(3H,m,Ar-H),4.06(1H,d,J＝12.8Hz,-CH₂Ph),3.96(1H,d,J＝12.8Hz,-CH₂Ph),3.03(1H,hept,J＝6.8Hz,-CH(CH₃)₂),2.51(1H,q,J＝7.2Hz,-CH₂),2.50(1H,q,J＝7.2Hz,-CH₂)1.30(3H,d,J＝7.2Hz,-CH₃),1.24(3H,t,J＝7.2Hz,-CH₃),1.16(3H,d,J＝6.8Hz,-CH₃).¹³C NMR(100MHz,CDCl₃)δ141.6,135.5,131.2,130.9,128.7,125.9,54.3,39.4,32.9,17.6,14.6,13.4.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₂H₁₈OS₃Na 297.0412;Found 297.0407.

EXAMPLE 31 Synthesis of Compound I-22

Referring to general disulfide construction step E, starting with compound III-03 (wherein R ² SH is benzyl mercaptan), a colourless oily liquid is obtained Ⅰ-22(683mg,88％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.79(1H,dd,J＝8.0,1.6Hz,Ar-H),7.42(1H,td,J＝7.6,1.6Hz,Ar-H),7.37(1H,td,J＝7.6,1.6Hz,Ar-H),7.31-7.17(6H,m,Ar-H),3.71-3.59(4H,m,-CH₂Ph),2.89(1H,hept,J＝6.8Hz,-CH(CH₃)₂),1.21(3H,d,J＝6.8Hz,-CH₃),1.09(3H,d,J＝6.8Hz,-CH₃).¹³C NMR(100MHz,CDCl₃)δ141.5,137.3,135.4,131.2,131.0,129.6,128.9,128.7,127.8,125.8,54.3,43.8,39.2,17.5,13.5.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₇H₂₀OS₃Na 359.0568;Found 359.0551.

EXAMPLE 32 Synthesis of Compound I-23

Referring to general disulfide construction step E, starting from compound III-03 (wherein R ² SH is 4-methoxybenzyl mercaptan), we obtain Ⅰ-23(744mg,88％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.84(1H,dd,J＝7.6,1.6Hz,Ar-H),7.47(1H,td,J＝7.2,1.2Hz,Ar-H),7.42(1H,td,J＝7.2,1.6Hz,Ar-H),7.27(1H,dd,J＝7.2,1.2Hz,Ar-H),7.19(2H,m,Ar-H),6.85(2H,m,Ar-H),3.78(3H,s,-OCH₃),3.75(1H,d,J＝12.8Hz,-CH₂Ph),3.70(1H,d,J＝12.8Hz,-CH₂Ph),3.69(1H,d,J＝12.8Hz,-CH₂Ph),3.66(1H,d,J＝12.8Hz,-CH₂Ph),2.95(1H,m,-CH(CH₃)₂),1.26(3H,d,J＝6.8Hz,-CH₃),1.14(3H,d,J＝6.8Hz,-CH₃).¹³C NMR(150MHz,CDCl₃)δ159.4,141.6,135.5,131.2,131.0,130.7,129.2,128.7,125.8,114.3,55.5,54.3,43.2,39.2,17.5,13.5.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₈H₂₂O₂S₃Na 389.0674;Found 389.0679.

EXAMPLE 33 Synthesis of Compound I-24

Referring to general disulfide construction step D, starting with compound III-04 (wherein R ² SM is sodium methyl mercaptide), we obtain Ⅰ-24(250mg,75％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.80-7.78(1H,m,Ar-H),7.67-7.63(2H,m,Ar-H),7.47-7.37(6H,m,Ar-H),4.17(1H,d,J＝13.2Hz,-CH₂Ph),4.10(1H,d,J＝13.2Hz,-CH₂Ph),2.15(3H,s,-CH₃).¹³C NMR(100MHz,CDCl₃)δ144.9,144.3,136.4,131.6,131.3,131.2,129.5,129.3,126.6,125.8,38.8,23.3.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₄H₁₄OS₃Na 317.0099;Found 317.0101.

EXAMPLE 34 Synthesis of Compound I-25

Referring to general disulfide construction step D, compound III-05 is used as starting material (wherein R ² SM is sodium thiophenoxide) to obtain Ⅰ-25(2.55g,91％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.82(1H,dd,J＝8.0,1.6Hz,Ar-H),7.47-7.36(5H,m,Ar-H),7.32(1H,td,J＝7.6,1.2Hz,Ar-H),7.29-7.24(3H,m,Ar-H),7.23-7.16(3H,m,Ar-H),4.16(1H,d,J＝13.2Hz,-CH₂Ph),4.04(1H,d,J＝13.2Hz,-CH₂Ph),2.34(3H,s,-CH₃).¹³C NMR(100MHz,CDCl₃)δ144.2,141.9,141.5,136.7,135.1,131.4,131.3,130.2,129.3,129.2,128.2,127.4,126.1,126.0,39.5,21.6.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₂₀H₁₈OS₃Na 393.0412;Found 393.0413.

EXAMPLE 35 Synthesis of Compound I-26

Referring to the general disulfide construction step E, compound III-05 is used as a starting material (wherein R ² SH is 4-methoxyphenylthiophenol), to obtain Ⅰ-26(395mg,87％for 2steps).¹H NMR(600MHz,CDCl₃)δ7.81(1H,dd,J＝7.8,1.2Hz,Ar-H),7.38-7.43(3H,m,Ar-H),7.33-7.37(3H,m,Ar-H),7.29(1H,dd,J＝7.8,1.2Hz,Ar-H),7.19(2H,d,J＝8.4Hz,Ar-H),6.78-6.81(2H,m.Ar-H),4.16(1H,d,J＝13.2Hz,-CH₂Ph),4.05(1H,d,J＝13.2Hz,-CH₂Ph),3.77(s,3H,-OMe),2.34(s,3H,-CH₃).¹³C NMR(150MHz,CDCl₃)δ160.0,144.4,141.8,141.6,135.4,132.6,131.4,131.3,130.2,129.3,127.6,126.2,126.0,114.9,55.6,39.4,21.6.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₂₁H₂₀O₂S₃Na 423.0518;Found 423.0510.

EXAMPLE 36 Synthesis of Compound I-27

Referring to general disulfide construction step D, starting from compound III-05 (wherein R ² SM is sodium methyl mercaptide), we obtain Ⅰ-27(300mg,85％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.83(1H,dd,J＝7.6,1.6Hz,Ar-H),7.53(2H,d,J＝8.0Hz,Ar-H),7.46-7.36(3H,m,Ar-H),7.25-7.23(2H,m,Ar-H),4.12(1H,d,J＝13.2Hz,-CH₂Ph),4.06(1H,d,J＝13.2Hz,-CH₂Ph),2.35(3H,s,-CH₃),2.14(3H,s,-CH₃).¹³C NMR(100MHz,CDCl₃)δ144.4,141.8,141.7,136.1,131.4,131.2,130.2,129.3,126.3,126.0,38.8,23.3,21.6.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₅H₁₆OS₃Na 331.0255;Found 331.0260.

EXAMPLE 37 Synthesis of Compound I-28

Referring to general disulfide construction step D, using compound III-06 as starting material (wherein R ² SM is sodium thiophenol), a colorless liquid can be obtained Ⅰ-28(26mg,82％for 2steps).¹H NMR(600MHz,CDCl₃)δ7.69(1H,dd,J＝7.8,1.2Hz,Ar-H),7.55-7.52(2H,m,Ar-H),7.40(1H,t,J＝7.2Hz,Ar-H),7.33(2H,t,J＝7.8Hz,Ar-H),7.28(1H,d,J＝7.2Hz,Ar-H),7.27-7.25(1H,m,Ar-H),4.16(2H,s,-CH₂Ph),2.91(1H,hept,J＝6.6Hz,-CH(CH₃)₂),2.73(1H,q,J＝7.2Hz,-CH₂CH₃),2.72(1H,q,J＝7.2Hz,-CH₂CH₃),1.21(6H,m,-CH₃),1.09(1H,d,J＝7.2Hz,-CH₃).¹³C NMR(151MHz,CDCl₃)δ144.9,142.8,136.8,131.5,131.0,129.3,129.2,129.0,127.8,123.6,54.3,36.7,25.3,17.8,15.4,13.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₈H₂₂OS₃Na 373.0725;Found373.0724.

EXAMPLE 38 Synthesis of Compound I-29

Referring to general disulfide construction step D, starting with compound III-07 (wherein R ² SM is sodium thiophenol), a colorless oily liquid can be obtained Ⅰ-29(30mg,73％for 2steps).¹H NMR(600MHz,CDCl₃)δ8.41(1H,s),7.90-7.88(1H,m),7.75-7.73(1H,m),7.68(1H,s),7.58-7.56(2H,m),7.54-7.51(2H,m),7.42-7.38(3H,m),7.37-7.35(2H,m),7.18-7.15(2H,m),7.11-7.08(1H,m),4.13(1H,d,J＝13.2Hz),4.06(1H,d,J＝13.2Hz).¹³C NMR(150MHz,CDCl₃)δ144.7,141.0,136.7,134.3,132.7,131.7,131.2,130.8,129.7,129.1,128.8,128.4,128.3,127.9,127.4,127.2,126.7,40.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₂₃H₁₈OS₃Na 429.0412;Found 429.0417.

EXAMPLE 39 Synthesis of Compound I-30

Referring to general disulfide construction step D, compound III-08 (wherein R ² SM is sodium thiophenol) is used as starting material to obtain colorless liquid Ⅰ-30(55mg,55％for 2steps).¹H NMR(600MHz,CDCl₃)δ7.85(1H,d,J＝7.8Hz,Ar-H),7.45-7.43(3H,m,Ar-H),7.39(1H,t,J＝7.2Hz,Ar-H),7.33(1H,d,J＝7.8Hz,Ar-H),7.27(2H,t,J＝7.8Hz,Ar-H),7.20(1H,t,J＝7.8Hz,Ar-H),4.13(1H,d,J＝12.6Hz,-CH₂Ph),3.95(1H,d,J＝12.6Hz,-CH₂Ph),3.75-3.71(2H,m),3.67-3.56(6H,m),3.21(1H,quint.J＝6.0Hz,-SCH),2.34-2.17(4H,m).¹³C NMR(150MHz,CDCl₃)δ141.1,136.6,134.9,131.5,131.4,129.2,128.9,128.1,127.4,125.5,66.9,64.3,64.0,63.5(t,J＝3.7Hz),63.2(t,J＝3.4Hz),38.6,31.5(t,J＝21.5Hz),31.4(t,J＝21.6Hz).HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₃₂H₂₄F₂₆O₃S₃Na 1069.0365;Found 1069.0363.

EXAMPLE 40 Synthesis of Compound I-31

Referring to general disulfide construction step D, compound III-09 (wherein R ² SM is sodium thiophenol) is used as starting material to obtain colorless liquid Ⅰ-31(64mg,70％for 2steps).¹H NMR(400MHz,CDCl₃)δ7.56-7.47(7H,m,Ar-H),7.32-7.28(2H,m,Ar-H),7.23-7.20(1H,m,Ar-H),2.92-2.74(4H,m),2.21-2.10(1H,m),2.06-1.95(1H,m).¹³C NMR(150MHz,CDCl₃)δ143.7,137.1,131.3,129.5,129.3,128.2,127.3,124.2,55.4,37.3,21.4.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₅H₁₆OS₃Na 331.0253;Found 331.0255.

EXAMPLE 41 preparation of Compound I in the hundred gram scale (exemplified by the Synthesis of Compound I-02)

After synthesis of II-01 according to literature (J.org.chem., 2011,76,1513-1520), 170g of II-01 were weighed into a reaction flask, 56mL of acetic acid was added, 395mL of 30wt% aqueous hydrogen peroxide solution was slowly added dropwise at room temperature using a constant pressure dropping funnel, and the reaction was maintained at room temperature until the reaction was complete. Subsequently, a sufficient amount of water was added to the reaction flask, and after stirring thoroughly, the mixture was suction-filtered under reduced pressure and lyophilized to obtain a white solid III-01 (171 g, 92%). The resulting III-01 was placed in a multi-necked flask, 292g of sodium thiosulfate pentahydrate and 0.9L of water were added, and the reaction was heated at 50℃for 4 hours until TLC monitoring the complete conversion of compound III-01. The above reaction solution was cooled to 0 ℃ without any post-treatment operation, 0.53L of methylene chloride and p-tolylthiophenol (124 g,1.1 eq) were added in this order, and an aqueous solution of potassium carbonate (125 g,1.0 eq, C _{Potassium carbonate}＝0.8M,v_{Water and its preparation method} = 1.13L) was added dropwise to the reaction system using a peristaltic pump (the addition time was 2.5 hours). After completion of the dropwise addition, the reaction was continued for 30 minutes at 0℃and then diluted with methylene chloride, washed three times with water, and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated by filtration, and purified by recrystallization to give a white solid I-02 (254 g,91% for2 steps).

The glycosyl donors (IV) referred to in examples 42-72 wherein:

The compounds IV-01 to IV-03, IV-05 to IV-09, IV-15, IV-17, IV-22 can be synthesized according to a similar method for synthesizing the compound 2 in the literature (org. Biomol. Chem.,2019,17,8379-8383);

Compounds IV-10, IV-11 were synthesized as described in the respective references (org. Lett.,2020,22,6584-658, org. Lett.,2005,7,4653-4656);

Compound IV-04 can be synthesized according to the following synthetic route:

Commercially available peracetylglucose S8 (1.0 g,2.56 mmol) and 2, 6-dimethylbenzene thiophenol (430 mg,3.07 mmol) were weighed out, and the powder was added Molecular sieves (200 mg) and anhydrous dichloromethane (6.0 mL) were added dropwise with triflic acid (180. Mu.L, 2.05 mmol) under ice-bath. After 2 hours of reaction, the addition of saturated sodium bicarbonate solution was terminated. The reaction solution was extracted with ethyl acetate, washed with water and then with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was recrystallized from ethyl acetate/petroleum ether to give IV-04 as a white solid (900 mg, 75%). R _f =0.53 (petroleum ether-ethyl acetate) 2:1).¹H NMR(600MHz,CDCl₃)δ7.15(1H,dd,J＝8.4,6.6Hz,Ar-H),7.09(2H,d,J＝7.2Hz,Ar-H),5.15(1H,t,J＝9.6Hz),5.08(1H,t,J＝9.6Hz),5.03(1H,t,J＝9.6Hz),4.39(1H,d,J＝9.6Hz,H-1),4.13(1H,dd,J＝12.0,6.0Hz),4.02(1H,dd,J＝12.0,1.8Hz),3.49-3.47(1H,m),2.50(6H,s,-CH₃),2.10(3H,s,-COCH₃),2.00(3H,s,-COCH₃),1.99(3H,s,-COCH₃),1.98(3H,s,-COCH₃).¹³C NMR(150MHz,CDCl₃)δ170.8,170.5,169.6,169.6,144.3,131.1,129.6,128.5,88.7,75.6,74.2,70.8,68.7,62.5,22.5,20.9,20.8,20.8,20.8.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₂₂H₂₈O₉SNa 491.1346;Found 491.1347.

Compound IV-12 can be synthesized according to a similar method to that described in literature (org. Lett.,2013,15,4904-4907) for the synthesis of compound 1 c;

compound IV-13 can be synthesized according to the literature (J carbohydrate chem.1997,16, 947-966);

Compounds IV-14, IV-16, IV-18, IV-21 can be synthesized according to the literature (org. Lett.,2004,6,3797-3800);

Compound IV-19 can be synthesized according to literature (J carbohydrate chem. 2007,26,349-368);

compound IV-20 can be synthesized according to the literature (Synthesis, 2007,9,1412-1420);

compound IV-23 can be synthesized according to literature (eur.j. Org. Chem.,2013, 6158-6166);

compound IV-24 can be synthesized according to the following synthetic route:

After S9 was synthesized according to the literature (Angew.chem.int.ed.2021, 60, 24859-24863), S9 (50 mg,0.18 mmol) was weighed and dissolved in anhydrous tetrahydrofuran (1.0 mL), carbonylimidazole (60 mg,0.37 mmol) was added, reacted at room temperature for 10 hours, tetrahydrofuran was removed by spinning, the reaction solution was extracted with ethyl acetate, washed with dilute hydrochloric acid, saturated brine in this order, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. To the crude product was added 4-dimethylaminopyridine (4.5 mg,0.04 mmol), dichloromethane (1.0 mL), triethylamine (51. Mu.L, 0.37 mmol) and benzoyl chloride (32. Mu.L, 0.028 mmol) in succession under ice-bath, and the reaction was continued at room temperature for 4 hours after the addition. The reaction solution was extracted with ethyl acetate, washed with water and then with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was recrystallized from methylene chloride/petroleum ether to give white flaky solid IV-24 (52 mg, 70%) R _f =0.38 (petroleum ether-ethyl acetate) 2:1).¹H NMR(600MHz,CDCl₃)δ8.02(2H,dd,J＝8.4,1.2Hz,Ar-H),7.62-7.59(1H,m,Ar-H),7.46(2H,t,J＝7.8Hz,Ar-H),7.36(2H,d,J＝8.4Hz,Ar-H),7.09(2H,d,J＝7.8Hz,Ar-H),5.16(1H,dd,J＝8.4,6.0Hz,H-2),4.98(1H,dd,J＝7.2,6.0Hz,H-3),4.91(1H,d,J＝8.4Hz,H-1),4.67(1H,dd,J＝7.2,1.8Hz,H-4),3.98(1H,qd,J＝6.6,2.4Hz,H-5),2.32(3H,s,-CH₃),1.47(3H,d,J＝6.6Hz,-CH₃).¹³C NMR(100MHz,CDCl₃)δ165.0,153.5,139.1,134.0,133.9,130.1,130.1,129.2,128.8,128.2,85.2,77.2,76.57,71.9,71.2,21.4,16.5.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₂₁H₂₀O₆SNa 423.0873;Found 423.0872.

Compound IV-25 can be synthesized according to literature (org. Biomol. Chem.,2019,17,2877-2882);

Compound IV-26 can be synthesized according to literature (carbohydrate.res. 2006,341,1702-1707);

Compound IV-27 can be synthesized according to the patent (CA 2646407A 1);

compound IV-28 can be synthesized according to the following synthetic route:

Commercial S11 (500 mg,1.92 mmol) was weighed out, anhydrous methylene chloride (3.7 mL) and p-methyl thiophenol (287 mg,2.30 mmol) were added under argon atmosphere, cooled to-40℃and boron trifluoride etherate solution (0.38 mL,2.88 mmol) was slowly added. The reaction was carried out at-40℃for 0.5h, followed by the addition of 1.0mL of triethylamine. The reaction system was diluted with ethyl acetate and washed successively with water, saturated sodium bicarbonate and saturated sodium chloride solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product was purified by silica gel column chromatography to give colorless syrup IV-28 (543 mg, 87%). R _f =0.51 (petroleum ether-ethyl acetate) 4:1).¹H NMR(600MHz,CDCl₃)δ7.40(2H,d,J＝7.8Hz,Ar-H),7.11(2H,d,J＝7.8Hz,Ar-H),5.18-5.16(2H,m),4.85-4.81(1H,m),4.11-4.07(1H,m),2.31(3H,s,-CH₃),2.06(3H,s,-COCH₃),2.02(3H,s,-COCH₃).¹³C NMR(150MHz,CDCl₃)169.9,169.7 138.8,134.3,129.9,128.0,87.7,78.6,75.3,74.3,21.3,20.8,20.7,19.5.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₁₆H₂₀O₅SNa,347.0924;Found 347.0922.

Compounds IV-29 may be described in accordance with the literature (Eur. J. Org. Chem.,2021, 4525-4530)

The glycosyl acceptor (V) of examples 42-72, wherein the compounds V-02, V-09, V-14, V-17, V21-V25 are commercially available;

Compound V-01 can be synthesized according to literature (Tetrahedron lett.,2017,58,2389-2392);

compound V-03 can be synthesized according to literature (carbohydro.res., -1982,108,97-102);

Compound V-04 can be synthesized according to literature (j.am.chem.soc. 2019,141,8509-8515);

Compound V-05 can be synthesized according to literature (chi. Chem. Lett.,2022,33,288-292);

Compound V-06 can be synthesized according to literature (carbohydro.res., -2017,452,35-42);

Compound V-07 can be synthesized according to literature (angel. Chem. Int. Ed.,2014,53,8190-8194);

Compound V-08 can be synthesized according to literature (carbohydro.res., 1981,92,154-156);

compound V-10 can be synthesized according to literature (org.chem. Front.,2019,6,3116-3120);

Compound V-11 can be synthesized according to literature (j. Org. Chem.,2007,72,10268-10271);

compound V-12 can be synthesized according to literature (bioorg. Med. Chem. Lett.,2020,30,127276);

compound V-13 can be synthesized according to literature (j.am.chem.soc. 2019,141,11775-11780);

compound V-15 can be synthesized according to literature (tetrahedron, 2003,59,3063-3087);

Compound V-16 can be synthesized according to the following synthetic route:

Acetic anhydride (0.23 mL,2.46 mmol) was added dropwise to a commercially available solution of S10 (200 mg,0.49 mmol) in anhydrous pyridine (2.0 mL) under ice-bath. After the addition, the reaction is naturally restored to room temperature and continued for 7 hours. The reaction solution was extracted with ethyl acetate, washed with dilute hydrochloric acid, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography to give colorless viscous liquid V-17 (151 mg, 68%). R _f = 0.45 (petroleum ether-ethyl acetate) 3:1).¹H NMR(600MHz,CDCl₃)δ4.58-4.53(1H,m,3α-H),3.83(1H,d,J＝1.2Hz,7α-H),3.64(3H,s,-OCH₃),2.36-2.18(3H,m),1.97(3H,s,-COCH₃),1.97-1.58(8H,m),1.49-1.22(10,m),1.18-1.08(4H,m),1.02(1H,td,J＝14.4,3.6Hz),0.90(3H,d,J＝6.6Hz,21-CH₃),0.89(3H,s,19-CH₃),0.64(3H,s,18-CH₃).¹³C NMR(150MHz,CDCl₃)δ175.0,171.0,74.6,68.7,56.0,51.7,50.7,42.9,41.4,39.8,39.6,35.6,35.5,35.3 35.2,34.6,33.0,31.2,31.2,28.4,26.9,23.9,23.0,21.7,20.8,18.5,12.0.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₂₇H₄₄O₅Na 471.3081;Found 471.3078.

Compound V-18 can be synthesized according to a similar method to that described in literature (j. Agric. Food chem.,2010,58,2138-2149) for the synthesis of compound 19;

Compound V-19 can be obtained according to the literature (Angew. Chem. Int. Ed.,2018,57,15866-15870)

Compound V-20 can be described in the literature (Eur. J. Med. Chem.,2009,44,4112-412)

Example 42 use of the Compounds of the general structural formula (I) according to the invention in glycosylation reactions

The compound with different substitutions shown in the structural general formula (I) is suitable for the model glycosylation reaction of glycosyl donor IV-01 and glycosyl acceptor V-01, and can be used for efficiently preparing disaccharide compound VI-01.

The experimental procedure was followed by weighing donor IV-01 (55 mg,0.12 mmol), acceptor V-01 (46 mg,0.1 mmol) and compound (I) (0.12 mmol), azeotropically dehydrating toluene, and adding the powderMolecular sieves (100 mg) and anhydrous dichloromethane (1.0 mL), pre-chilled to-40 ℃. Under argon, trifluoromethanesulfonic anhydride (20. Mu.L, 0.12 mmol) was added and reacted for 3 hours. The addition of triethylamine was terminated. The reaction solution was extracted with ethyl acetate, washed with water, saturated NaHCO ₃ solution, saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Separating and purifying the crude product by silica gel column chromatography to obtain colorless syrup Ⅵ-01.¹H NMR(400MHz,CDCl₃)δ7.39-7.19(15H,m,Ar-H),4.99(1H,t,J＝9.2Hz),4.95(1H,d,J＝12.0Hz,-CH₂Ph),4.92(1H,t,J＝9.2Hz),4.86(1H,t,J＝8.8Hz,H-2'),4.72-4.69(2H,m,-CH₂Ph),4.56(1H,d,J＝11.6Hz,-CH₂Ph),4.57-4.54(2H,m,-CH₂Ph),4.46(1H,d,J＝7.6Hz,H-1'),4.39(1H,d,J＝12.0Hz,-CH₂Ph),4.11(1H,dd,J＝12.4,4.0Hz),3.87-3.78(3H,m),3.73(1H,dd,J＝10.8,2.8Hz),3.59-3.55(2H,m),3.44(1H,dd,J＝8.8,3.6Hz,H-2),3.34(1H,s,-OCH₃),3.27(1H,m,H-5),1.97(3H,s,-COCH₃),1.95(3H,s,-COCH₃),1.92(3H,s,-COCH₃),1.92(3H,s,-COCH₃).

EXAMPLE 43 reactivity test of the Compound of the general formula (I) of the present invention after preservation in an air atmosphere at room temperature

After the compound with the structural general formula (I) is stably stored in an air atmosphere at room temperature for a certain time, the compound is used for glycosylation coupling between a glycosyl donor IV-01 and a glycosyl acceptor V-01. Take the example of the activating agents I-01, I-02:

The experimental procedure was carried out by weighing donor IV-01 (55 mg,0.12 mmol), acceptor V-01 (46 mg,0.1 mmol) and compound (I-01 or I-02) (0.12 mmol), azeotropically dehydrating toluene, and adding the powder Molecular sieves (100 mg) and anhydrous dichloromethane (1.0 mL), pre-chilled to-40 ℃. Under argon, trifluoromethanesulfonic anhydride (20. Mu.L, 0.12 mmol) was added and reacted for 3 hours. The addition of triethylamine was terminated. The reaction solution was extracted with ethyl acetate, washed with water, saturated NaHCO ₃ solution, saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product is separated and purified by silica gel column chromatography to obtain colorless syrup VI-01.

EXAMPLE 44 application of the Compound of the general formula (I) of the present invention in glycosylation

The compound can effectively activate glycosyl donors IV-01-IV-11 with different substitutions at C1 positions to cause glycosylation reaction with a model glycosyl acceptor V-01, and the disaccharide compound VI-01 is efficiently prepared. Taking the example of the activating reagent I-09:

The specific experimental operation comprises weighing any one (0.12 mmol) of donor IV-01-IV-11, acceptor V-01 (46 mg,0.1 mmol) and activating reagent I-09 (38.7 mg,0.12 mmol), azeotropically removing water from toluene, and adding powder Molecular sieves (100 mg) and anhydrous dichloromethane (1.0 mL), pre-chilled to-40 ℃. Under argon, trifluoromethanesulfonic anhydride (20. Mu.L, 0.12 mmol) was added and reacted for 3 hours. The addition of triethylamine was terminated. The reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product is separated and purified by silica gel column chromatography to obtain a colorless syrup compound VI-01.

EXAMPLE 45 use of the Compounds of the general formula (I) according to the invention in glycosylation reactions

The compound can activate the model glycosyl donor IV-01 in a temperature range of-78-30 ℃ to synthesize the disaccharide compound VI-01. Taking the example of the activating reagent I-11:

The specific experimental procedure comprises weighing glycosyl donor IV-01 (55 mg,0.12 mmol), glycosyl acceptor V-01 (46 mg,0.1 mmol) and activating reagent I-11 (42 mg,0.12 mmol), azeotropically dehydrating toluene, and adding the newly activated powder Molecular sieves (100 mg) and anhydrous dichloromethane (1.0 mL), pre-chilled to a specific temperature (as indicated in the table above). Under the protection of argon, trifluoromethanesulfonic anhydride (20 mu L,0.12 mmol) was added for a specified period of time (as shown in the above table; in addition, other reaction periods of time than the specified periods of time in the above table may be employed, and the higher the reaction temperature, the shorter the corresponding reaction period of time may be). The addition of Et ₃ N was terminated. The reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product is separated and purified by silica gel column chromatography to obtain a colorless syrup compound VI-01.

Comparative example 1 use of Compounds of the general structural formula (VII) in glycosylation reactions

The detailed experimental procedure was to weigh glycosyl donor IV-01 (55 mg,0.12 mmol), glycosyl acceptor V-01 (46 mg,0.1 mmol) and activating reagent VII (49 mg,0.12 mmol), azeotropically remove water from toluene, and add the freshly activated powderMolecular sieves (100 mg) and anhydrous dichloromethane (1.0 mL), pre-chilled to a specific temperature. Under the protection of argon, trifluoromethanesulfonic anhydride (20. Mu.L, 0.12 mmol) was added and reacted for a specified period of time. The addition of triethylamine was terminated. The reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product is separated and purified by silica gel column chromatography to obtain a colorless syrup compound VI-01.

Example 46 use of the Compounds of the general structural formula (I) according to the invention in glycosylation reactions

The compound can activate glycosyl donor IV-01 in halogenated hydrocarbon solvents, aromatic hydrocarbon solvents, nitrile solvents and ether solvents to synthesize disaccharide compound VI-01. Taking reagent I-09 as an example:

The experimental procedure comprises weighing donor IV-01 (55 mg,0.12 mmol), acceptor V-01 (46 mg,0.1 mmol) and activating reagent I-09 (38.7 mg,0.12 mmol), azeotropically dehydrating toluene, adding powder Molecular sieves and anhydrous solvent (1.0 mL), pre-chilled to-40 ℃. Under argon, trifluoromethanesulfonic anhydride (20. Mu.L, 0.12 mmol) was added and reacted for 3 hours. The addition of triethylamine was terminated. The reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product is separated and purified by silica gel column chromatography to obtain a colorless syrup compound VI-01.

Example 47 application of the Compound of the general formula (I) of the invention in glycosylation

Sub-stoichiometric amounts of the compounds of formula (I) are used for the activation of glycosyl donors IV-13, exemplified by activating reagents I-01, I-02, I-03, I-04, I-07, I-09, I-11, I-20, I-24, I-25, I-28, I-29, I-30, and I-31.

The specific experimental procedure was to weigh donor IV-13 (72 mg,0.12 mmol), acceptor V-01 (46 mg,0.1 mmol) and activating reagent formula (I) (0.06 mmol), remove water from toluene azeotropically, add 2, 6-di-tert-butyl-4-methylpyridine (25 mg,0.12 mmol), powderMolecular sieves (100 mg) and anhydrous dichloromethane (1.0 mL), pre-chilled to 0 ℃. Under argon, trifluoromethanesulfonic anhydride (20 μl,0.12 mmol) was added. After 1 hour of reaction, the temperature was raised to 30℃and the reaction was continued for 3 hours. The reaction mixture was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. Separating and purifying the crude product by silica gel column chromatography to obtain colorless syrup compound Ⅵ-02.¹H NMR(400MHz,CDCl₃)δ7.39-7.19(15H,m,Ar-H),4.99(1H,t,J＝9.2Hz),4.95(1H,d,J＝12.0Hz,-CH₂Ph),4.92(1H,t,J＝9.2Hz),4.86(1H,t,J＝8.8Hz,H-2'),4.72-4.69(3H,m,-CH₂Ph),4.56(1H,d,J＝11.6Hz,-CH₂Ph),4.57-4.54(2H,m,-CH₂Ph),4.46(1H,d,J＝7.6Hz,H-1'),4.39(1H,d,J＝12.0Hz,-CH₂Ph),4.11(1H,dd,J＝12.4,4.0Hz),3.87-3.78(3H,m),3.73(1H,dd,J＝10.8,2.8Hz),3.59-3.55(2H,m),3.44(1H,dd,J＝8.8,3.6Hz,H-2),3.34(1H,s,-OCH₃),3.27(1H,m,H-5),1.97(3H,s,-COCH₃),1.95(3H,s,-COCH₃),1.92(3H,s,-COCH₃),1.92(3H,s,-COCH₃).

Examples 48 to 72 use of the Compounds of the general formula (I) according to the invention in glycosylation reactions

Unless otherwise indicated, the glycosylation reactions of examples 47-71 can be performed according to the following three standard procedures:

Reaction Standard procedure A glycosyl donor (1.2 eq), acceptor (1.0 eq) and compound of formula (I) (1.2 eq) were weighed out and toluene azeotropically dehydrated. Adding a dry material Molecular sieves (100 mg/mL in CH ₂Cl₂ solution) and anhydrous dichloromethane (to give a concentration of the acceptor c=0.1M), pre-chilled to-40 ℃ or 0 ℃. Under argon, trifluoromethanesulfonic anhydride (1.2 eq.) was added and the reaction was completed until the starting material was completely converted. The reaction mixture was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. And separating and purifying the crude product by silica gel column chromatography to obtain the target glycosylation product.

Reaction Standard procedure B glycosyl donor (1.2 eq.) and compound of formula (I) (1.2 eq.) were weighed and the toluene azeotropically dehydrated. Adding a dry materialMolecular sieves (100 mg/mL in CH ₂Cl₂ solution) and anhydrous dichloromethane (giving a donor concentration of c=0.1M), pre-chilled to-40 ℃. Under argon, trifluoromethanesulfonic anhydride (1.2 eq.) was added and the reaction was completed until the donor conversion was complete. Subsequently, a dichloromethane solution of the acceptor (1.0 equivalent) was added (to give a concentration c=0.1m) and the reaction was continued until the conversion of the acceptor was complete. The reaction mixture was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. And separating and purifying the crude product by silica gel column chromatography to obtain the target glycosylation product.

Reaction Standard procedure C glycosyl donor (1.2 eq), acceptor (1.0 eq) and compound of formula (I) (0.6 eq) were weighed out and toluene azeotropically dehydrated. 2, 6-Di-tert-butyl-4-methylpyridine (1.2 eq.) was added and driedMolecular sieves (100 mg/mL in CH ₂Cl₂ solution), and anhydrous dichloromethane (to give a concentration of the acceptor c=0.1M), pre-chilled to 0 ℃. Under argon, trifluoromethanesulfonic anhydride (0.6 eq.) was added. The reaction was carried out at 0℃for 1 hour, followed by heating to 30℃until complete conversion of the starting material. The addition of triethylamine was terminated. The reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. And separating and purifying the crude product by silica gel column chromatography to obtain the target glycosylation product.

EXAMPLE 48 Synthesis of Oxoid VI-03

Referring to reaction standard procedure A, colorless syrup VI-03 (15.4 mg, 85%) was obtained. R _f =0.30 (petroleum ether-ethyl acetate) 2:1).¹H NMR(600MHz,CDCl₃)δ7.96(1H,d,J＝7.2Hz,Ar-H),7.52(1H,t,J＝7.2Hz Ar-H),7.36(2H,t,J＝7.8Hz,Ar-H),7.33-7.30(4H,m,Ar-H),7.27-7.18(9H,m,Ar-H),7.14-7.13(2H,m,Ar-H),5.25(1H,t,J＝5.4Hz),5.15(1H,d,J＝5.4Hz),4.89(1H,dd,J＝7.8,4.2Hz),4.72(1H,d,J＝11.4Hz),4.60(1H,dd,J＝7.8,2.4Hz),4.56(1H,d,J＝8.4Hz,H-1'),4.56(3H,d,J＝11.4Hz),4.37(1H,d,J＝11.4Hz),4.21(1H,d,J＝11.4Hz),4.12(1H,d,J＝2.4Hz,H-1),3.89-3.84(2H,m),3.81(1H,dd,J＝9.6,2.4Hz),3.74-3.70(2H,m),3.58(1H,dd,J＝9.6,5.4Hz),3.30(3H,s,-OCH₃),1.36(3H,d,J＝6.6Hz,-CH₃).¹³C NMR(150MHz,CDCl₃)δ164.8,153.7,139.0,138.6,138.6,133.8,130.2,129.3,128.7,128.5,128.5,128.5,128.1,127.9,127.8,127.7,127.7,127.7,100.4,98.6,78.4,76.6,75.8,75.6,73.9,73.8,73.7,71.3,69.5,69.2,67.7,55.5,16.5.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₄₂H₄₄O₁₂Na 763.2725;Found 763.2718.

EXAMPLE 49 Synthesis of Oxoid VI-04

Referring to reaction standard procedure B, 2, 6-di-tert-butyl-4-methylpyridine (14 mg,1.2 eq.) was added along with donor and activating reagent to give VI-04 as a white foamy solid (38 mg, 96%). R _f =0.23 (petroleum ether-ethyl acetate) 4:1).¹H NMR(400MHz,CDCl₃)δ7.49(1H,dd,J＝7.6,2.0Hz,Ar-H),7.43-7.25(13H,m,Ar-H),5.88(1H,d,J＝4.0Hz,H-1),5.61(1H,s),4.86(1H,d,J＝12.0Hz),4.81(1H,d,J＝11.6Hz),4.75(1H,d,J＝12.8Hz),4.62(1H,d,J＝12.4Hz),4.55(1H,s,H-1'),4.43-4.38(2H,m),4.30-4.26(3H,m),4.21(1H,t,J＝9.6Hz),4.11(1H,dd,J＝8.8,6.4Hz),4.04(1H,dd,J＝8.4,6.0Hz),3.90(1H,t,J＝10.0Hz),3.85(1H,d,J＝2.0Hz),3.60(1H,dd,J＝10.0,3.2Hz),3.34-3.28(1H,m),1.48(3H,s),1.42(3H,s),1.32(3H,s),1.29(3H,s).

EXAMPLE 50 Synthesis of Oxoid VI-05

Referring to reaction standard procedure B, 2, 6-di-tert-butyl-4-methylpyridine (15 mg,1.2 eq.) was added along with donor and activating reagent to give VI-05 as a white foamy solid (32 mg, 92%). R _f =0.35 (petroleum ether-ethyl acetate) 10:1).¹H NMR(400MHz,CDCl₃)δ7.49(4H,dd,J＝8.0,2.0Hz,Ar-H),7.39-7.23(11H,m,Ar-H),5.60(1H,s,Benzylidene-H),5.01(1H,d,J＝12.4Hz,-CH₂Ph),4.92(1H,d,J＝12.4Hz,-CH₂Ph),4.74(1H,s,H-1),4.66(1H,d,J＝12.4Hz,-CH₂Ph),4.57(1H,d,J＝12.4Hz,-CH₂Ph),4.24(1H,dd,J＝10.4,4.8Hz H-6a),4.19(1H,t,J＝9.6Hz,H-4),3.92(1H,t,J＝10.4Hz,H-6b),3.76(1H,d,J＝2.4Hz,H-2),3.58(1H,dd,J＝10.0,3.2Hz,H-3),3.33-3.27(1H,m),2.15(3H,br s),1.85-1.73(6H,m),1.66-1.58(6H,m).

EXAMPLE 51 Synthesis of Oxoid VI-06

Referring to reaction standard procedure A, colorless syrup VI-06 (37 mg, 93%) was obtained. R _f =0.11 (petroleum ether-acetone) 3:1).¹H NMR(400MHz,CDCl₃)δ7.35-7.25(15H,m,Ar-H),5.52(1H,dd,J＝8.8,1.6Hz),5.42-5.37(1H,m),4.90(1H,d,J＝10.8Hz),4.80-4.72(4H,m),4.64(1H,d,J＝12.0Hz),4.63(1H,dd,J＝9.2,2.0Hz),4.59(1H,d,J＝3.6Hz,H-1),4.42-4.15(2H,m),3.98-3.91(2H,m),3.84(1H,d,J＝12.4,6.4Hz),3.77-3.73(1H,m),3.68(3H,s),3.61(1H,dd,J＝11.2,9.2Hz),3.53(1H,dd,J＝10.0,8.8Hz),3.50(1H,dd,J＝10.0,3.6Hz),3.45(1H,dd,J＝10.8,2.0Hz),3.35(3H,s),2.89(1H,dd,J＝12.0,3.6Hz),2.09(3H,s),2.07(1H,dd,J＝13.6,12.0Hz),1.99(3H,s),1.74(3H,s).

EXAMPLE 52 Synthesis of Oxoid VI-07

Referring to reaction Standard procedure A, 2, 6-di-tert-butyl-4-methylpyridine DTBMP (11 mg,1.2 eq.) was additionally added to give colorless syrup Ⅵ-07(28mg,91％).¹H NMR(400MHz,CDCl₃)δ¹H NMR(400MHz,CDCl₃)δ7.33-7.22(15H,m,Ar-H),5.50(1H,dd,J＝2.8,53.2Hz,H-1),5.13(1H,t,J＝8.8,8.4Hz),4.94(3H,m),4.80(3H,m,PhCH₂),4.67(1H,d,J＝12.0Hz,PhCH₂),4.53(1H,d,J＝10.8Hz,PhCH₂),4.48(1H,d,J＝6.8Hz),4.09(1H,dd,J＝4.8,11.6Hz,H-6a),4.00(1H,dd,J＝1.6,11.2Hz,H-6b),3.95(1H,t,J＝9.2,9.6Hz),3.90(1H,m,H-5),3.76(1H,dd,J＝3.6,11.2Hz,H-5a'),3.57(1H,t,J＝9.6,10.0Hz),3.50(1H,ddd,J＝2.4,9.6,12.0Hz,H-2),3.29(1H,dd,J＝8.8,11.6Hz,H-5b'),2.02(3H,s,CH₃),2.02(3H,s,CH₃),1.99(3H,s,CH₃),1.92(3H,s,CH₃).¹³C NMR(101MHz,CDCl₃)δ170.33,170.00,169.46,138.58,138.07,137.76,128.78,128.64,128.32,128.26,128.19,128.10,127.94,106.77(d,J＝230Hz,C-1),100.61,81.48,79.51(d,J＝20Hz),76.69,76.00,75.34,73.79,72.44,72.40(d,J＝6Hz),71.77,70.96,68.91,67.19,20.94,20.91,20.84.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₃₈H₄₃O₁₂FNa 733.2631;Found 733.2616.

EXAMPLE 53 Synthesis of Oxoid VI-08

Referring to reaction standard procedure B, colorless syrup VI-08 (37 mg, 95%) was obtained. R _f =0.33 (petroleum ether-ethyl acetate 3:1) R _f =0.33 (petroleum ether-ethyl acetate) 3:1).¹H NMR(600MHz,CDCl₃)δ7.92(2H,dd,J＝6.6,1.8Hz,Ar-H),7.90(2H,dd,J＝7.2,1.2Hz,Ar-H),7.80(2H,dd,J＝7.2,1.2Hz,Ar-H),7.50(1H,t,J＝7.8Hz,Ar-H),7.44-7.34(6H,m,Ar-H),7.30-7.22(15H,m,Ar-H),7.15-7.14(2H,m,Ar-H),5.80(1H,t,J＝9.6Hz),5.53(1H,dd,J＝9.6,7.8Hz,H-2'),5.32(1H,t,J＝9.6Hz),4.91(1H,d,J＝10.8Hz,-CH₂Ph),4.86(1H,d,J＝10.8Hz,-CH₂Ph),4.83(1H,d,J＝7.8Hz,H-1'),4.69(1H,d,J＝10.8Hz,-CH₂Ph),4.64(1H,d,J＝10.2Hz,-CH₂Ph),4.63(1H,d,J＝10.8Hz,-CH₂Ph),4,51(1H,d,J＝7.8Hz,H-1),4.43(1H,d,J＝10.8Hz,-CH₂Ph),4.22(1H,dd,J＝15.6,2.4Hz),4.17-4,14(2H,m),3.84-3.80(1H,m),3.68(1H,dd,J＝10.8,6.0Hz),3.59(1H,t,J＝9.0Hz),3.48-3.46(1H,m),3.39(1H,t,J＝9.6Hz),3.37(1H,t,J＝9.0Hz),2.44(1H,t,J＝2.4Hz),1.36(3H,d,J＝6.0Hz,H-6').¹³C NMR(150MHz,CDCl₃)δ166.1,165.6,165.2,138.7,138.5,138.2,133.5,133.3,133.3,130.0,129.9,129.5,129.3,129.1,128.6,128.6,128.6,128.5,128.5,128.0,128.0,127.9,127.9,127.8,101.5,101.1,84.6,82.0,79.3,77.7,75.8,75.1,75.0,74.9,74.7,74.1,73.2,72.3,70.8,68.4,56.1,17.8.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₅₇H₅₄O₁₃Na 969.3457;Found969.3451.

EXAMPLE 54 Synthesis of Oxoid VI-09

Referring to reaction standard procedure C, colorless syrup VI-09 (42 mg, 93%) was obtained. R _f =0.23 (petroleum ether-ethyl acetate) 8:1).¹H NMR(400MHz,CDCl₃)δ7.95(2H,d,J＝8.0,1.2,Ar-H),7.42(1H,tt,J＝7.6,1.2Hz,Ar-H),7.32-7.20(20H,m,Ar-H),7.10-7.07(2H,m,Ar-H),5.08(1H,dd,J＝6.4,3.2Hz,H-2'),4.92(1H,d,J＝6.4Hz,H-1'),4.89(1H,d,J＝11.2Hz,-CH₂Ph),4.72(1H,d,J＝12.0Hz,-CH₂Ph),4.71(1H,d,J＝11.2Hz,-CH₂Ph),4.58(1H,d,J＝12.0Hz,-CH₂Ph),4.58(1H,d,J＝12.0Hz,-CH₂Ph),4.51(1H,d,J＝10.8Hz,-CH₂Ph),4.49(1H,d,J＝12.0Hz,-CH₂Ph),4.47(1H,d,J＝3.6Hz,H-1),4.16-4.12(1H,m),3.95-3.74(5H,m),3.70-3.65(3H,m),3.47-3.42(2H,m),3.21(3H,s,-OCH₃),0.82(9H,s),0.81(9H,s),0.01(3H,s),0.04(3H,s),0.02(3H,s),-0.01(3H,s).¹³C NMR(100MHz,CDCl₃)δ165.4,139.1,138.6,138.4,138.4,133.1,130.1,130.0,128.6,128.5,128.5,128.5,128.4,128.3,128.0,128.0,127.8,127.7,127.7,127.6,100.2,98.2,82.2,79.9,79.5,77.7,75.7,75.1,75.1,73.6,73.5,71.2,71.1,69.8,67.9,55.2,26.1,18.2,18.1,-3.8,-4.1,-4.1,-4.3.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₆₀H₈₀O₁₂Si₂Na 1071.5081;Found 1071.5065.

EXAMPLE 55 Synthesis of Oxoid VI-10

Following addition of the acceptor to triflic anhydride at-40 ℃ in accordance with reaction standard procedure C, colorless syrup VI-10 (27 mg, 81%) was obtained. R _f =0.43 (petroleum ether-ethyl acetate) 2:1).¹H NMR(400MHz,CDCl₃)δ7.32-7.21(13H,m,Ar-H),7.11(2H,m,Ar-H),6.95-6.91(2H,m,Ar-H),6.74-6.70(2H,m,Ar-H),5.34(1H,dd,J＝3.2,1.6Hz),5.25(1H,t,J＝9.6Hz),5.19(1H,t,J＝9.6Hz),5.03(1H,t,J＝9.6Hz),4.88(1H,d,J＝7.6Hz,H-1),4.84(1H,d,J＝1.6Hz,H-1'),4.83(1H,d,J＝10.4Hz),4.67(1H,d,J＝10.8Hz),4.63(1H,d,J＝12.0Hz),4.51(1H,d,J＝10.8Hz),4.47(1H,d,J＝10.8Hz),4.46(1H,d,J＝12.0Hz),3.91(1H,dd,J＝9.2,3.2Hz),3.85(1H,t,J＝9.2Hz),3.81-3.69(4H,m),3.65(1H,dd,J＝10.8,1.6Hz),3.54-3.51(1H,m),3.53(3H,s,-OCH₃),2.12(3H,s,-COCH₃),2.06(3H,s,-COCH₃),2.02(3H,s,-COCH₃),2.00(3H,s,-COCH₃).¹³C NMR(100MHz,CDCl₃)δ170.6,170.5,169.6,169.5,156.0,151.1,138.7,138.3,138.1,128.6,128.5,128.4,128.2,127.9,127.8,127.8,127.6,119.4,114.8,100.8,97.8,78.4,75.2,74.3,73.5,73.1,72.8,72.3,71.7,71.5,69.2,68.9,68.8,66.3,55.6,21.3,20.9,20.8.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₄₈H₅₄O₁₆Na 909.3304;Found 909.3267.

EXAMPLE 56 Synthesis of Oxoid VI-11

Referring to reaction standard procedure C, colorless syrup VI-11 (29 mg, 93%) was obtained. R _f =0.29 (petroleum ether-ethyl acetate) 3:1).¹H NMR(400MHz,CDCl₃)δ8.09(2H,d,J＝7.2Hz,Ar-H),7.69(1H,t,J＝3.6Hz,Ar-H),7.55(2H,t,J＝8.0Hz,Ar-H),7.47-7.39(9H,m,Ar-H),7.29(1H,td,J＝7.6,0.8Hz,Ar-H),7.26(3H,m,Ar-H),7.17(1H,t,J＝7.6Hz,Ar-H),5.43-5.35(3H,m),5.16(1H,dd,J＝3.2,10.4Hz),5.06(1H,d,J＝13.2Hz,-CH₂Ph),4.97(1H,d,J＝13.2Hz,-CH₂Ph),4.93(1H,d,J＝10.8Hz,-CH₂Ph),4.87(1H,d,J＝11.2Hz,-CH₂Ph),4.84(1H,d,J＝9.6Hz,-CH₂Ph),4.81(1H,d,J＝12.0Hz,-CH₂Ph),4.78(1H,d,J＝8.4Hz,H-1),4.68(1H,d,J＝8.4Hz,H-1'),4.32(1H,dd,J＝2.4,12.4Hz),4.04(1H,d,J＝11.2Hz),3.95-3.85(3H,m),3.57-3.55(1H,m),3.37(1H,m,-CH(CH₃)₂),2.32(3H,s,-COCH₃),2.29(3H,s,-COCH₃),2.13(3H,s,-COCH₃),1.35(3H,d,J＝6.4Hz),1.31(3H,d,J＝6.8Hz),1.30(3H,d,J＝6.4Hz).

EXAMPLE 57 Synthesis of Oxoid VI-12

Referring to reaction standard procedure C, colorless syrup VI-12 (30 mg, 91%) was obtained. R _f =0.32 (petroleum ether-ethyl acetate) 4:1).R_f＝0.32(petroleum ether-EtOAc 4:1).¹H NMR(400MHz,CDCl₃)δ8.00(4H,td,J＝8.0,0.8Hz,Ar-H),7.84(2H,dd,J＝8.4,1.2Hz,Ar-H),7.58-7.54(1H,m,Ar-H),7.51-7.46(2H,m,Ar-H),7.41(2H,t,J＝8.0Hz,Ar-H),7.34-7.26(4H,m,Ar-H),5.77-5.70(3H,m),4.84(1H,s),4.71(1H,td,J＝6.8,4.8Hz),4.64(1H,dd,J＝11.6,4.8Hz),4.55(1H,dd,J＝11.2,6.4Hz),4.20-4.17(1H,m),4.09-4.07(1H,m),3.64-3.58(2H,m),3.34(3H,s,-OCH₃),1.52(3H,s,-CH₃),1.30(3H,s,-CH₃),1.29(3H,d,J＝6.0Hz,-CH₃).

EXAMPLE 58 Synthesis of Oxoid VI-13

Referring to reaction standard procedure C, colorless syrup VI-13 (30 mg, 98%) was obtained. R _f =0.25 (petroleum ether-ethyl acetate) 4:1).¹H NMR(400MHz,CDCl₃)δ7.45-7.42(2H,m,Ar-H),7.36-7.31(3H,m,Ar-H),5.59(1H,s,-CHPh),5.34-5.29(1H,m,H-3'),5.11(1H,s,H-1),5.03(1H,d,J＝1.2Hz,H-4'),4.96(1H,d,J＝2.8Hz,H-1'),4.46(1H,d,J＝4.4Hz,H-2),4.27-4.22(2H,m,H-5,H-5),3.98(1H,t,J＝9.2Hz,H-4),3.91(1H,td,J＝10.0,4.0Hz,H-6a),3.86(1H,t,J＝10.0Hz,H-6b),3.42(1H,dd,J＝4.4,9.2Hz,H-3),3.36(3H,s,-OCH₃),2.10(3H,s,-COCH₃),2.03(1H,td,J＝12.4,3.6Hz,H-2a'),1.95(3H,s,-COCH₃),1.87(1H,dd,J＝4.8,12.0Hz,H-2b'),0.82(1H,d,J＝6.4Hz,H-6').

EXAMPLE 59 Synthesis of Oxoid VI-14

Referring to reaction standard procedure C, colorless syrup VI-14 (19 mg, 95%) was obtained. R _f =0.24 (petroleum ether-ethyl acetate) 1.5:1).¹H NMR(400MHz,CDCl₃)δ8.30(2H,d,J＝8.8Hz,Ar-H),8.05(2H,d,J＝8.8Hz,Ar-H),6.32(1H,s,-NH),5.24-5.18(2H,m,H-3,H-4),5.08(1H,d,J＝2.8Hz,H-1),4.65(1H,d,J＝3.6Hz,H-1'),4.13-4.08(1H,m,H-5),3.83-3.76(1H,m,H-5'),3.34(3H,s,-OCH₃),3.09(1H,d,J＝9.2Hz,H-4'),2.13(3H,s,-COCH₃),2.07-1.93(3H,m,H-2a',H-2a,H-2b),2.01(3H,s,-COCH₃),1.65(1H,dd,J＝4.0,14.4Hz,H-2b'),1.35(3H,s,-CH₃),1.24(3H,d,J＝6.8Hz,H-6'),1.09(3H,d,J＝6.8Hz,H-6).

EXAMPLE 60 Synthesis of Oxoid VI-15 (this example illustrates the Synthesis of a glycosidic bond)

Referring to reaction standard procedure C, colorless syrup VI-15 (56 mg, 96%) was obtained. R _f =0.21 (petroleum ether-ethyl acetate) 5:1).¹H NMR(400MHz,CDCl₃)δ7.97-7.04(30H,m,Ar-H),5.54(1H,s,Benzylidene-H),5.03(1H,d,J＝10.4Hz,-CH₂Ph),4.89(1H,d,J＝10.8Hz,-CH₂Ph),4.88(1H,d,J＝3.6Hz),4.88(1H,d,J＝9.2Hz,-CH₂Ph),4.85(1H,d,J＝10.4Hz,-CH₂Ph),4.84(1H,d,J＝3.6Hz),4.79(1H,d,J＝12.0Hz,-CH₂Ph),4.74(1H,d,J＝10.4Hz,-CH₂Ph),4.70(1H,d,J＝12.0Hz,-CH₂Ph),4.56(1H,d,J＝10.8Hz,-CH₂Ph),4.36-4.27(3H,m),4.16-4.08(3H,m),3.87-3.81(2H,m),3.70(1H,t,J＝10.0Hz),3.61-3.54(3H,m),3.44(3H,s).¹³C NMR(100MHz,CDCl₃)δ166.3,138.8,138.5,138.4,138.1,137.6,133.2,130.3,130.0,129.2,128.9,128.7,128.7,128.6,128.5,128.5,128.4,128.2,128.2,128.2,128.0,128.0,127.9,126.2,101.5,97.3,94.4,82.9,82.3,79.6,77.9,76.1,75.8,75.3,74.5,73.2,69.3,69.1,63.2,62.4,55.2.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₅₅H₅₆O₁₂Na 931.3664;Found 931.3726.

Example 61 Synthesis of Oxoid VI-16 (this example illustrates the Synthesis of two glycosidic linkages)

Referring to reaction Standard procedure C, donor IV-16 (48 mg,0.080 mmol), acceptor V-10 (14 mg,0.0034 mmol), activating reagent I-02 (12.3 mg,0.040 mmol), 2, 6-di-tert-butyl-4-methylpyridine (16 mg,0.080 mmol) and trifluoromethanesulfonic anhydride (7. Mu.L, 0.040 mmol). Colorless syrup VI-16 (35.9 mg, 81%) was obtained. R _f =0.14 (petroleum ether-ethyl acetate) 2:1).¹H NMR(400MHz,CDCl₃)δ7.35-7.08(40H,m,Ar-H),5.35(1H,t,J＝10.4Hz),5.33(1H,t,J＝10.4Hz),5.07(1H,d,J＝12.0Hz),5.03(1H,d,J＝12.0Hz),4.94(1H,d,J＝11.2Hz),4.93(1H,d,J＝11.6Hz),4.91(1H,d,J＝11.2Hz),4.79(1H,d,J＝9.6Hz),4.67(1H,d,J＝12.4Hz),4.60(1H,d,J＝12.4Hz),4.57(1H,d,J＝4.4Hz,H-1a),4.54-4.46(4H,m),4.45(1H,d,J＝8.4Hz,H-1b),4.41(1H,d,J＝12.4Hz),4.39(1H,d,J＝11.6Hz),4.32(1H,d,J＝7.6Hz,H-1c),4.23(1H,d,J＝11.6Hz),4.14(1H,d,J＝12.0Hz),4.02(1H,d,J＝10.4Hz),3.95(1H,d,J＝2.0Hz),3.88(1H,d,J＝2.4Hz),3.88-3.83(1H,m),3.66-3.45(9H,m),3.41-3.34(3H,m),3.25(3H,s,-OCH₃),3.20(1H,dd,J＝8.4,4.4Hz),1.97(3H,s,-COCH₃),1.96(3H,s,-COCH₃).¹³C NMR(100MHz,CDCl₃)δ170.1,169.5,156.2,139.4,138.9,138.6,138.2,138.2,138.1,138.0,136.6,128.7,128.6,128.6,128.4,128.3,128.3,128.3,128.1,128.1,128.1,128.0,127.9,127.9,127.9,127.8,127.8,127.6,127.4,127.1,117.8,101.8,101.7,98.5,80.5,80.3,78.7,78.6,75.0,74.7,73.8,73.7,73.5,73.4,72.9,72.8,72.0,71.8,71.3,70.9,68.7,68.2,67.6,67.0,55.1,54.6,21.2,21.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₈₀H₈₇NO₁₉Na 1388.5765;Found 1388.5812.

EXAMPLE 62 Synthesis of Oxoid VI-17

Referring to reaction Standard procedure C, white solid VI-17 (39 mg, 92%) was obtained. R _f =0.24 (petroleum ether-ethyl acetate) 3:1).¹H NMR(400MHz,CDCl₃)δ7.80-7.10(23H,m,Ar-H),5.76(1H,d,J＝8.8,Hz,NH),4.93(1H,dd,J＝8.8,8.4Hz,H-2),4.79(1H,d,J＝11.6Hz),4.78(1H,d,J＝11.2Hz),4.66(1H,d,J＝11.6Hz),4.55(2H,d,J＝11.6Hz),4.49(1H,d,J＝12.0Hz),4.41-4.29(4H,m),4.36(1H,d,J＝8.0Hz,H-1),4.23(1H,t,J＝7.2Hz),3.74-3.61(4H,m),3.66(3H,s,-OCH₃),3.40(1H,m,H-5),1.95(3H,s,-COCH₃),1.18(3H,d,J＝6.4Hz).

EXAMPLE 63 Synthesis of Oxoid VI-18

Referring to reaction standard procedure C, white foam VI-18 (34 mg, 83%) was obtained. R _f =0.42 (petroleum ether-ethyl acetate) 5:1).¹H NMR(600MHz,CDCl₃)δ7.33-7.25(13H,m,Ar-H),7.18(2H,dd,J＝7.8,1.8Hz,Ar-H),4.98(1H,dd,J＝9.6,7.8Hz,H-2),4.79(1H,d,J＝11.4Hz,-CH₂Ph),4.75(1H,d,J＝10.8Hz,-CH₂Ph),4.65(1H,d,J＝11.4Hz,-CH₂Ph),4.58(1H,d,J＝12.0Hz,-CH₂Ph),4.57(1H,d,J＝10.8Hz,-CH₂Ph),4.57-4.51(1H,m),4.51(1H,d,J＝12.0Hz,-CH₂Ph),4.46(1H,d,J＝7.8Hz,H-1),3.89(1H,d,J＝1.8Hz),3.72-3.68(3H,m),3.65(3H,s),3.63(1H,t,J＝9.6Hz),3.41(1H,ddd,J＝9.6,4.2,1.8Hz,H-5),2.36-2.31(1H,m),2.22-2.17(1H,m),2.06-1.99(2H,m),1.98(3H,s,-COCH₃),1.96(3H,s,-COCH₃),1.90-1.88(1H,m),1.84-1.81(2H,m),1.78-1.68(3H,m),1.64-1.57(2H,m),1.52-1.47(3H,m),1.42-1.38(3H,m),1.35-1.28(2H,m),1.25-1.11(4H,m),0.99(1H,td,J＝11.4,3.0Hz),0.91-0.87(7H,m),0.60(3H,s,-CH₃).¹³C NMR(150MHz,CDCl₃)δ175.0,170.9,169.7,138.5,138.5,138.2,128.6,128.6,128.6,128.3,128.0,127.8,127.8,127.8,127.7,97.1,83.7,78.4,75.2,75.1,75.1,74.9,73.9,73.5,72.7,69.2,55.4,51.6,49.4,42.7,41.5,39.3,39.2,35.5,35.3,35.3,34.9,32.7,31.2,29.2,28.3,27.1,23.4,22.9,21.7,21.4,20.8,18.6,12.0.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₅₆H₇₄O₁₁Na 945.5123;Found 945.5113.

EXAMPLE 64 Synthesis of Oxoid VI-19

Following addition of the acceptor to triflic anhydride at-40 ℃ in accordance with reaction standard procedure C, colorless syrup VI-19 (39 mg, 95%) was obtained. R _f =0.17 (petroleum ether-ethyl acetate) 2:1).¹H NMR(400MHz,CDCl₃)δ7.35-7.26(13H,m,Ar-H),7.21-7.19(2H,m,Ar-H),7.14(1H,s,Ar-H),6.45(1H,s,Ar-H),6.33(2H,Ar-H),5.94(2H,dd,J＝8.0,1.2Hz),5.41(1H,dd,J＝10.0,8.0Hz,H-2),4.91(1H,d,J＝11.6Hz,-CH₂Ph),4.85(1H,d,J＝10.0Hz,-CH₂Ph),4.65(1H,d,J＝12.0Hz,-CH₂Ph),4.57(1H,d,J＝12.0Hz,-CH₂Ph),4.56-4.51(2H,m),4.48(1H,d,J＝12.4Hz,-CH₂Ph),4.40(1H,d,J＝9.2Hz,H-1),4.39(2H,br s,-CH₂Ph),4.03(1H,t,J＝9.6Hz),3.91(1H,d,J＝2.4Hz,H-4),3.76(3H,s,-OCH₃),3.71(6H,s,-OCH₃),3.61-3.46(4H,m),2.90-2.79(1H,m),2.74(1H,dd,J＝14.4,4.4Hz),1.98(3H,s,-COCH₃).

EXAMPLE 65 Synthesis of Oxoid VI-20

Referring to reaction standard procedure C, colorless syrup VI-20 (32.2 mg, 81%) was obtained. R _f =0.47 (petroleum ether-ethyl acetate) 7:1).¹H NMR(600MHz,CDCl₃)δ7.42-7.39(2H,m,Ar-H),7.28-7.19(17H,m,Ar-H),5.15(1H,br s),5.05(1H,t,J＝9.6Hz),4.88-4.82(4H,m),4.69(1H,d,J＝12.0Hz),4.59-4.50(5H,m),4.09(1H,d,J＝10.2Hz),3.87-3.84(1H,m),3.70-3.66(2H,m),3.58-3.56(1H,m),3.51(1H,t,J＝9.0Hz),3.34-3.28(1H,m),2.44-2.38(1H,m),2.19-2.14(1H,m),1.71-1.66(1H,m),1.61-1.56(1H,m),1.44-1.39(1H,m),1.32-1.29(1H,m),1.24-1.21(9H,m),1.11(6H,t,J＝6.6Hz),1.03(3H,d,J＝6.0Hz),0.86(3H,t,J＝7.2Hz),0.78(3H,t,J＝7.2Hz).¹³C NMR(10MHz,CDCl₃)δ176.9,176.3,175.8,175.7,169.8,155.0,150.5,149.8,143.1,142.9,138.6,138.3,136.4,128.5,128.5,128.4,128.1,127.9,127.8,124.9,123.8,121.6,111.0,108.8,107.8,98.7,79.9,79.0,78.2,75.5,74.3,72.0,68.7,68.2,39.5,39.3,39.3,29.9,27.4,27.4,27.3,21.2,18.1.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₅₇H₇₀O₁₅Na1017.4607;Found 1017.4639.

EXAMPLE 66 Synthesis of phenolic glycoside VI-21

Referring to reaction standard procedure A, colorless syrup VI-21 (31 mg, 97%) was obtained. R _f =0.27 (petroleum ether-ethyl acetate) 2:1).¹H NMR(400MHz,CDCl₃)δ7.06(2H,d,J＝9.2Hz,Ar-H),6.99(2H,d,J＝9.2Hz,Ar-H),5.51(1H,dd,J＝10.0,3.6Hz,H-3),5.46(1H,d,J＝1.6Hz,H-1),5.40(1H,dd,J＝3.6,2.0Hz,H-2),5.33(1H,t,J＝10.0Hz,H-4),4.25(1H,dd,J＝12.4,5.6Hz),4.08-4.03(2H,m),2.25(3H,s),2.17(3H,s),2.03(3H,s),2.01(3H,s),2.00(3H,s).¹³C NMR(100MHz,CDCl₃)δ170.7,170.1,170.1,169.9,169.8,153.4,146.1,122.8,117.4,96.3,69.5,69.4,69.0,66.1,62.3,21.2,21.0,20.9,20.8.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₂₂H₂₆O₁₂Na 505.1316;Found 505.1337.

EXAMPLE 67 Synthesis of ester glycoside VI-22

Referring to reaction standard procedure C, colorless syrup VI-22 (39 mg, 89%) was obtained. R _f =0.44 (petroleum ether-ethyl acetate) 5:1).¹H NMR(400MHz,CDCl₃)δ7.36-7.26(11H,m,Ar-H),5.98(1H,d,J＝1.6Hz,H-1),5.28-5.25(2H,m),4.91(1H,d,J＝11.2Hz),4.70(1H,d,J＝11.2Hz),4.62(1H,d,J＝10.8Hz),4.53-4.45(2H,m),3.84(1H,dd,J＝9.2,3.2Hz),3.81-3.74(1H,m),3.46(1H,t,J＝9.6Hz),2.81(1H,dd,J＝13.6,4.0Hz),2.15(3H,s),2.02(3H,s),1.95(1H,td,J＝13.6,4.0Hz),1.83(2H,dd,J＝8.8,3.2Hz),1.27(3H,d,J＝6.0Hz),1.11(3H,s),0.91(3H,s),0.89(3H,s),0.87(3H,s),0.85(3H,s),0.83(3H,s),0.76(3H,s).¹³C NMR(100MHz,CDCl₃)δ175.1,171.2,170.2,143.4,138.5,137.8,128.7,128.6,128.3,128.2,128.1,128.0,123.2,90.9,81.1,79.7,77.9,75.7,72.1,70.4,68.3,55.6,47.7,47.3,45.8 42.0,41.7,39.6,38.4,37.9,37.1,33.9,33.2,33.1,32.6,30.9,28.3,27.7,26.0,23.8,23.7,23.6,23.1,21.5,21.2,18.4,18.2,17.4,16.9,15.6.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₅₄H₇₄O₉Na 889.5225;Found889.5221.

EXAMPLE 68 Synthesis of pyrimidine nucleoside VI-23

The pretreatment of the receptor for the silicon etherification comprises weighing the receptor V-21 (26 mg,0.23 mmol), adding acetonitrile (0.6 mL) and N, O-bis (trimethylsilane) trifluoroacetamide (BSTFA, 123 mu L) in sequence under the protection of argon, and reacting for 0.5 hours at room temperature to obtain the receptor for the silicon etherification V-21'.

Reference was made to reaction standard procedure B, donor IV-15 (35 mg,1.0 eq), reagent I-02 (29 mg,1.2 eq), triflic anhydride (16. Mu.L, 1.2 eq). After 10 minutes of anhydride addition, an acetonitrile solution of the above-described silicon etherification acceptor V-21' was added. White solid VI-23 (33.0 mg, 97%) was obtained. R _f =0.43 (petroleum ether-ethyl acetate) 1:3).¹HNMR(400MHz,CDCl₃)δ8.78(1H,br s,NH),8.10-8.08(2H,m,Ar-H),7.96-7.86(7H,m,Ar-H),7.62-7.46(9H,m,Ar-H),7.35(4H,t,J＝8.0Hz,Ar-H),6.44(1H,d,J＝4.8Hz,H-1'),5.90(1H,t,J＝5.6Hz),5.83(1H,t,J＝5.2Hz),4.85(1H,dd,J＝12.0,2.8Hz),4.79-4.76(1H,m),4.71(1H,dd,J＝12.4,4.0Hz).

EXAMPLE 69 Synthesis of pyrimidine nucleoside VI-24

The pretreatment of the receptor for the silicon etherification comprises weighing the receptor V-22 (46 mg,0.21 mmol), adding acetonitrile (0.6 mL) and N, O-bis (trimethylsilane) trifluoroacetamide (BSTFA, 112 μL) in sequence under the protection of argon, and reacting for 0.5 hours at room temperature to obtain the receptor for the silicon etherification V-22'.

Reference was made to reaction standard procedure B, donor IV-27 (40 mg,1.0 eq.), reagent I-09 (27 mg,1.2 eq.), triflic anhydride (14. Mu.L, 1.2 eq.). After 10 minutes of anhydride addition, an acetonitrile solution of the above-described silicon etherification acceptor V-22' was added. White solid VI-24 (43 mg, 93%) was obtained. R _f =0.45 (petroleum ether-ethyl acetate) 1:1).¹HNMR(400MHz,CDCl₃)δ8.78(1H,br s,NH),8.10-8.08(2H,m,Ar-H),7.96-7.86(7H,m,Ar-H),7.62-7.46(9H,m,Ar-H),7.35(4H,t,J＝8.0Hz,Ar-H),6.44(1H,d,J＝4.8Hz,H-1'),5.90(1H,t,J＝5.6Hz),5.83(1H,t,J＝5.2Hz),4.85(1H,dd,J＝12.0,2.8Hz),4.79-4.76(1H,m),4.71(1H,dd,J＝12.4,4.0Hz).

EXAMPLE 70 Synthesis of pyrimidine nucleoside VI-25

The pretreatment of the receptor for the silicon etherification comprises weighing the receptor V-23 (37 mg,0.28 mmol), adding acetonitrile (0.7 mL) and N, O-bis (trimethylsilane) trifluoroacetamide (BSTFA, 149 mu L) in sequence under the protection of argon, and reacting for 0.5 hour at room temperature to obtain the receptor for the silicon etherification V-23'.

Reference was made to reaction standard procedure B, donor IV-28 (30 mg,1.0 eq), reagent I-02 (34 mg,1.2 eq), triflic anhydride (15. Mu.L, 1.2 eq). After 10 minutes of anhydride addition, an acetonitrile solution of the above-described silicon etherification acceptor V-23' was added. Obtaining colorless syrup Ⅵ-25(30mg,98％).¹H NMR(600MHz,CDCl₃)δ9.61(brs,1H),7.36(d,J＝5.4Hz,1H),5.94(d,J＝4.8Hz,1H),5.29(t,J＝5.4Hz,1H),5.01(t,J＝5.4Hz,1H),4.24-4.19(m,1H),2.11(s,3H),2.09(s,3H),1.45(d,J＝6.6Hz,3H).

EXAMPLE 71 Synthesis of purine nucleoside VI-26

The reaction was carried out at 30℃for 24 hours, referring to reaction standard procedure C. Obtaining colorless syrup Ⅵ-26(32mg,94％).¹H NMR(400MHz,CDCl₃)δ8.26(1H,s,H-8),8.05-8.80(4H,m,Ar-H),7.92-7.90(2H,m,Ar-H),7.61-7.52(3H,m,Ar-H),7.46-7.34(6H,m,Ar-H),6.46(1H,d,J＝5.2Hz,H-1'),6.16(1H,t,J＝5.6Hz),6.11(1H,dd,J＝5.6,4.0Hz),4.90(1H,dd,J＝12.0,3.2Hz),4.85(1H,dd,J＝7.6,4.0Hz),4.71(1H,dd,J＝12.0,4.0Hz).

EXAMPLE 72 Synthesis of C-glycoside VI-27

Reference was made to reaction standard procedure B, donor IV-19 (30 mg,1.0 eq), reagent I-09 (21 mg,1.2 eq), 2, 6-di-tert-butyl-4-methylpyridine (13 mg,1.2 eq), trifluoromethanesulfonic anhydride (11. Mu.L, 1.2 eq). After 10 minutes of anhydride addition, enol silyl ether acceptor V-25 was added. A white foamy solid VI-27 (25 mg, 85%) was obtained. R _f =0.28 (petroleum ether-ethyl acetate) 7:1).¹H NMR(600MHz,CDCl₃)δ7.81(2H,dd,J＝8.4,1.2Hz,Ar-H),7.56(1H,tt,J＝7.2,1.2Hz,Ar-H),7.52(2H,dd,J＝7.8,1.2Hz,Ar-H),7.43(4H,t,J＝7.8Hz,Ar-H),7.40-7.34(5H,m,Ar-H),7.31-7.26(3H,m,Ar-H),7.17-7.14(2H,m,Ar-H),7.12-7.09(1H,m,Ar-H),5.65(1H,s,-CHPh),5.02(1H,d,J＝12.0Hz,-CH₂Ph),4.95(1H,d,J＝12.6Hz,-CH₂Ph),4.80(1H,d,J＝12.0Hz,-CH₂Ph),4.61(1H,d,J＝11.4Hz,-CH₂Ph),4.26(1H,dd,J＝10.8,2.4Hz,H-6a),4.25(1H,dd,J＝10.2,1.2Hz,H-6b),4.16-4.14(1H,m,H-1),4.05(1H,dd,J＝3.0,1.2Hz,H-2),3.88(1H,dd,J＝10.2,3.0Hz,H-3),3.82(1H,t,J＝10.2Hz,H-4),3.47(1H,td,J＝10.2,4.8Hz),3.24(1H,dd,J＝18.0,4.8Hz),3.13(1H,dd,J＝18.0,7.8Hz).¹³C NMR(150MHz,CDCl₃)δ197.5,138.8,138.2,137.9,136.7,133.5,129.0,128.7,128.6,128.5,128.4,128.3,128.0,127.8,127.8,126.3,101.6,80.7,79.6,76.2,75.8,75.3,73.5,72.1,68.8,39.8.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₃₅H₃₄O₆Na573.2248;Found 505.2233.

The above examples are only examples, and other types of bases (e.g., sodium hydroxide, potassium hydroxide, sodium carbonate, potassium phosphate) may be used instead of potassium carbonate, and the amount of the base may be preferably controlled to be 0.5 to 1.0 in terms of the molar ratio of the compound of the general structural formula (III) to the base.

It will be readily appreciated by those skilled in the art that the foregoing description is merely a preferred embodiment of the invention and is not intended to limit the invention, but any modifications, equivalents, improvements or alternatives falling within the spirit and principles of the invention are intended to be included within the scope of the invention.

Claims

1. An asymmetric disulfide compound containing sulfoxide groups is characterized by having a structure shown in a structural general formula (I):

Wherein S is a sulfur atom, and O is an oxygen atom;

r ¹ is selected from methyl, ethyl, isopropyl, phenyl, 4-methylphenyl and

X is selected from And (CH ₂)₂).

2. The sulfoxide group-containing asymmetric disulfide compound according to claim 1, wherein the sulfoxide group-containing asymmetric disulfide compound has a structural formula of any one of the formulas I-01 to I-31:

3. The process for producing a sulfoxide group-containing asymmetric disulfide compound according to claim 1 or 2, wherein the compound having a sulfide structure represented by the general structural formula (II) and having a leaving group is used as a starting material,

Wherein S is a sulfur atom, O is an oxygen atom, LG is a leaving group;

r ¹ is selected from methyl, ethyl, isopropyl, phenyl, 4-methylphenyl and

X is selected fromAnd (CH ₂)₂;

The preparation method specifically comprises the following steps:

The reaction scheme is as follows:

Wherein M in R ² SM is an alkali metal element;

4. The method according to claim 3, wherein in the step (S1), the oxidizing agent is m-chloroperoxybenzoic acid (m-CPBA) or Eosin Y (Eosin Y) or a mixture of hydrogen peroxide (H ₂O₂) -acid, wherein when the oxidizing agent is a mixture of hydrogen peroxide (H ₂O₂) -acid, the acid is any one of acetic acid and diphenyl phosphate;

5. The method of claim 3, wherein in the general structural formula (II), LG is preferably a bromine atom, a chlorine atom or a p-toluenesulfonyl group;

m is preferably sodium or potassium.

6. Use of an asymmetric disulfide compound containing sulfoxide groups as claimed in claim 1 or 2 as an activating reagent in glycosylation reactions.

7. The method according to claim 6, wherein the asymmetric disulfide compound containing sulfoxide groups is involved in activating a glycosyl donor to realize the connection between glycosyl units or the connection between glycosyl units and non-glycosyl units.

8. The method according to claim 6, wherein the glycosylation product represented by formula (VI) is obtained by using a composition of an activating reagent represented by the general structural formula (I) and trifluoromethanesulfonic anhydride as an accelerator to carry out glycosylation reaction between a glycosyl donor represented by the general structural formula (IV) and an acceptor represented by the general structural formula (V) in an organic solvent, wherein the reaction equation is as follows:

9. The use according to claim 6 wherein in the receptor represented by Gly or formula (V) the sugar is independently selected from any of D-glucose, D-galactose, D-mannose, L-rhamnose, D-xylose, D-quinolone, D-fucose, L-fucose, 2-deoxy-L-fucose, D-ribose, 6-deoxy-D-ribose, sialic acid, D-furanose, 2-amino-2-deoxy-D-glucose, 3-aminopolydeoxy-sugar;

the reaction temperature range of the glycosylation reaction is-78-30 ℃.

10. The use according to claim 6, wherein the glycosyl donor represented by the general structural formula (IV) is specifically any one of the compounds of the structural formulae IV-01 to IV-29: