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WO2005049547A1 - Procede pour la preparation de derives de 1,2,3,4-cyclohexanetetrol - Google Patents

Procede pour la preparation de derives de 1,2,3,4-cyclohexanetetrol Download PDF

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Publication number
WO2005049547A1
WO2005049547A1 PCT/IB2004/003782 IB2004003782W WO2005049547A1 WO 2005049547 A1 WO2005049547 A1 WO 2005049547A1 IB 2004003782 W IB2004003782 W IB 2004003782W WO 2005049547 A1 WO2005049547 A1 WO 2005049547A1
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formula
compound
protecting group
reducing agent
alkali metal
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Chandra Has Khanduri
Jayachandra Suresh Babu
Purna Chandra Ray
Jigar Bhaskarbhai Shah
Yatendra Kumar
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Ranbaxy Laboratories Ltd
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Ranbaxy Laboratories Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Definitions

  • voglibose is (lS)-(l(OH),2,4,5/l,3)-5-[[2-hydroxy-l-(hydroxymethyl) ethyl] amino]-l-C-(hydroxymethyl)- 1,2,3, 4-cyclohexanetetrol, and has been disclosed as being an excellent inhibitory activity against glucoside hydrolase.
  • Several processes have been reported for the preparation of voglibose such as in U.S. Patent Nos. 4,701,559, 4,824,943, 4,898,986, 6,150,568; J. Org. Chem., 57:3651 (1992) and J. Med. Chem., 29:1038 (1986).
  • Valiolamine which is chemically known as (lS)-(l(OH),2,4,5/l,3)-5-amino-l- hydroxymethyl-l,2,3,4-cyclohexanetetrol, has been disclosed as having ⁇ -glucosidase inhibitory activity and is a key intermediate for the preparation of voglibose. It has been prepared by synthetic and fermentation procedures disclosed in U.S. Patent Nos. 4,827,036 and 4,446,319; and Carbohydr. Res., 140:180 (1985). U.S. Patent No. 4,824,943 and J. Org.
  • Chem., 57:3651 (1992) disclose a process for the preparation of valiolamine comprising reacting (lS)-(l(OH),2,4/l,3)-2,3,4-tri-O- benzyl-5-oxo-l-C-[benzyloxymethyl]-l,2,3,4-cyclohexanetetrol with hydroxylamine hydrochloride to obtain (lS)-(l(OH),2,4,5/l,3)-2,3,4-tri-O-benzyl-5-(hydroxyimino)-l-C- [benzyloxymethyl]- 1,2,3,4-cyclohexanetetrol followed by reduction to yield (1S)- (l(OH),2,4,5/l,3)-2,3,4-tri-O-benzyl-5-amino-l-C-[benzyloxymethyl]-l,2,3,4- cyclohexanetetrol, which was further reduced to (lS)-(l(OH),2,4,5/l,3)-5-amino
  • U.S. Patent No. 4,898,986 discloses dechlorination of (lS)-(l(OH),2,4/l,3)-2,3,4- tri-O-benzyl-6,6-dichloro-5-oxo-l-C-[benzyloxymethyl]-l,2,3,4-cyclohexanetetrol in the presence of palladium - barium sulfate and sodium acetate at a pressure of 3 to 3.5 kg/cm 2 .
  • palladium - barium sulfate and sodium acetate at a pressure of 3 to 3.5 kg/cm 2 .
  • the reducing agent can be one or more of an alkali metal borohydride, an alkali metal aluminum hydride, an alkali metal cyanoborohydride, a metal catalyst in the presence of hydrogen, a dialkyl amine borane or mixtures thereof.
  • the alkali metal borohydride can be, for example, sodium borohydride, potassium borohydride, lithium borohydride, sodium trimethoxyborohydride or mixtures thereof;
  • the alkali metal aluminum hydride can be, for example, lithium aluminum hydride, sodium aluminum hydride or mixtures thereof;
  • the alkali metal cyanoborohydride can be, for example, sodium cyanoborohydride;
  • the metal catalyst can be, for example, palladium-carbon, palladium black, Raney-nickel, platinum black, platinum dioxide, rhodium carbon or mixtures thereof;
  • the dialkyl amine borane can be, for example, dimethylamine borane.
  • the hydroxyl-protecting group can be an acyl-type protecting group, an acetal- or ketal-type protecting group, or an ether-type protecting group.
  • the acyl-type protecting group can be, for example, an optionally substituted alkanoyl, benzoyl, alkoxycarbonyl, alkenyloxycarbonyl, benzyloxycarbonyl or phenyloxycarbonyl group;
  • the acetal- or ketal- type protecting group can be, for example, methylene, ethylene, isopropylidene or butylidene groups;
  • the ether-type protecting group can be, for example, an alkyl, alkenyl or benzyl group.
  • the reaction can be carried out in the presence of one or more solvent that is inert under reaction conditions.
  • solvents can be, for example, water, an alcohol, an ether, a chlorinated hydrocarbon, an ester, a nitrile, a ketone, a dipolar aprotic solvent, a cyclic ether or mixtures thereof.
  • the one or more reducing agent can be added simultaneously with ammonium acetate or ammonium formate or the one or more reducing agent can be added after the reaction of the compound of Formula II with ammonium acetate or ammonium formate.
  • the compound of Formula II can be prepared by dehalogenation of the compound of Formula III,
  • R can be a hydrogen atom or a hydroxyl protecting group and X can be halogen, for example, chlorine, bromine or iodine.
  • the hydroxyl-protecting group can be an acyl- type protecting group, an acetal- or ketal-type protecting group, or an ether-type protecting group.
  • the acyl-type protecting group can be, for example, an optionally substituted alkanoyl, benzoyl, alkoxycarbonyl, alkenyloxycarbonyl, benzyloxycarbonyl or phenyloxycarbonyl group; the acetal- or ketal-type protecting group can be, for example, methylene, ethylene, isopropylidene or butylidene groups; and the ether-type protecting group can be, for example, an alkyl, alkenyl or benzyl group.
  • dehalogenation can be carried out in the presence of reductive dehalogenating agent.
  • the reductive dehalogenating agent can be, for example, one or more of a metal catalyst in the presence of hydrogen, a metal hydride complex, an organic tin hydrides in the presence of radical initiator, an alkali metal aluminum hydride, or mixtures thereof.
  • the metal catalyst can be, for example, palladium-carbon, palladium black, Raney-Nickel, platinum black, platinum dioxide or mixtures thereof;
  • the metal hydride complex can be, for example, sodium borohydride, potassium borohydride, lithium borohydride, sodium trimethoxy borohydride or mixtures thereof;
  • the organic tin hydride can be, for example, tributyltin hydride, diethyltin hydride, triphenyl tin hydride or mixtures thereof; and the alkali metal aluminum hydride can be, for example, lithium aluminum hydride, sodium aluminum hydride or mixtures thereof.
  • the dehalogenation comprises hydrogenation at a pressure of at least 4.0 kg/cm 2 in the presence of a metal catalyst.
  • the hydrogenation can also be carried out at a about 4.0 kg/cm to about 6.0 kg/cm .
  • This reaction can be carried out in one or more solvent that is inert under reaction conditions.
  • solvents can be, for example, water, alcohol, ketone, ether, nitrile, chlorinated hydrocarbon, ester, dipolar aprotic solvent, cyclic ether or mixtures thereof.
  • solvents can be, for example, water, alcohol, ketone, ether, nitrile, chlorinated hydrocarbon, ester, dipolar aprotic solvent, cyclic ether or mixtures thereof.
  • reaction of the compound of Formula I with dihydroxyacetone can be carried out in the presence of an acid to maintain a pH in the range of from about 6 to about 6.5.
  • the compound of Formula I can be prepared by reacting the compound of Formula II
  • Formula II with ammonium acetate or ammonium formate and one or more reducing agent, to form a compound of Formula I.
  • the compound of Formula II can be formed by dehalogenating a compound of Formula III,
  • the compound of Formula II can be formed by dehalogenating a compound of Formula III,
  • R can be a hydrogen atom or hydroxyl protecting group and X can be halogen.
  • the one or more reducing agent can be one or more of an alkali metal borohydride, an alkali metal aluminum hydride, an alkali metal cyanoborohydride, a metal catalyst in the presence of hydrogen, a dialkyl amine borane or mixtures thereof.
  • the reaction of compound of Formula II with 2-amino-l,3-propanediol can be carried out in the presence of an acid to maintain a pH in the range of from about 7 to about 7.5.
  • the deprotection can be carried out by hydrogenation in the presence of metal catalyst and an acid to maintain a pH below 3. Also provided are processes for preparing voglibose comprising deprotecting a compound of Formula I
  • R when R is a hydroxyl protecting group to obtain valiolamine followed by reaction of valiolamine with dihydroxy acetone and one or more reducing agent, wherein R can be a hydrogen atom or a hydroxyl protecting group.
  • the one or more reducing agent can be one or more of an alkali metal borohydride, an alkali metal aluminum hydride, an alkali metal cyanoborohydride, a metal catalyst in the presence of hydrogen, a dialkyl amine borane or mixtures thereof.
  • the compound of Formula I can be prepared by reacting the compound of Formula II
  • the compound of Formula II can be formed by dehalogenating a compound of Formula III, Formula
  • R can be a hydrogen atom or hydroxyl protecting group and X can be halogen.
  • R can be a hydrogen atom or hydroxyl protecting group and X can be halogen.
  • R is a protecting group to obtain valiolamine followed by reaction of valiolamine with dihydroxy acetone and one or more reducing agent, wherein R can be a hydrogen atom or a hydroxyl protecting group.
  • R can be a hydroxyl protecting group and X can be a halogen.
  • the halogen can be, for example, F, Cl, Br or I.
  • the compounds provided herein can be further converted to its pharmaceutically acceptable salt, such as alkali, alkali earth or ammonium salt, by treating with suitable salt forming agent.
  • hydroxyl protecting groups include acyl-type protecting groups, acetal- or ketal-type protecting groups and ether-type protecting groups.
  • acyl-type protecting groups include optionally substituted alkanoyl, benzoyl, alkoxycarbonyl, alkenyloxycarbonyl, benzyloxycarbonyl or phenyloxycarbonyl group.
  • ether-type protecting groups include alkyl, alkenyl or benzyl groups.
  • acetal- or ketal-type protecting groups include methylene, ethylene, isopropylidene or butylidene groups.
  • the compound of Formula II can also be obtained by the process above or a conventional process, for example, a process disclosed in U.S. Patent Nos. 4,824,943 and 4,898,986; and J. Org.
  • the compound of Formula II can be prepared by dehalogenation of the compound of Formula III.
  • reducing agents include alkali metal borohydride, alkali metal aluminum hydride, alkali metal cyanoborohydride, dialkyl amine boranes, metal catalyst in the presence of hydrogen or mixtures thereof.
  • alkali metal borohydride include sodium borohydride, potassium borohydride, lithium borohydride, sodium trimethoxy borohydride or mixtures thereof.
  • An example of an alkali metal cyanoborohydride includes sodium cyanoborohydride.
  • metal catalysts include palladium-carbon, palladium black, Raney-nickel, platinum black, platinum dioxide, rhodium-carbon or mixtures thereof.
  • alkali metal aluminum hydrides include lithium aluminum hydride, sodium aluminum hydride or mixtures thereof.
  • An example of dialkyl amine borane includes dimethylamine borane.
  • the reducing agent can also be added after the reaction of compound of Formula II with ammonium acetate or ammonium formate, for example, when the reducing agent is a metal catalyst in the presence of hydrogen.
  • the reaction can be carried out in the presence of suitable solvents.
  • suitable solvents include, for example, organic solvents that are inert under reaction conditions.
  • solvents examples include water; alcohols, for example, methanol, ethanol, isopropanol or butanol; ketones, for example, acetone or methyl isobutyl ketone; ethers, for example, diethylether, diisopropylether or dimethoxyethane; nitriles, for example, acetonitrile; chlorinated hydrocarbons, for example, methylene chloride, ethylenedichloride or carbon tetrachloride; esters, for example, ethylacetate or isopropylacetate; dipolar aprotic solvents, for example, dimethylsulfoxide or dimethylformamide; cyclic ethers, for example, dioxane or tetrahydrofuran; or mixtures thereof.
  • alcohols for example, methanol, ethanol, isopropanol or butanol
  • ketones for example, acetone or methyl isobutyl ketone
  • ethers
  • the compound of Formula III can be prepared by processes disclosed in U.S. Patent No. 4,898,986 and J. Org. Chem., 57: 3642 (1992).
  • the dehalogenation reaction can be carried out in the presence of a reductive dehalogenating agent.
  • dehalogenating agents include one or more metal catalysts in the presence of hydrogen, the metal catalysts being, for example, palladium- carbon, palladium black, Raney-nickel, platinum black or platinum dioxide; metal hydride complexes, for example, sodium borohydride, potassium borohydride, lithium borohydride or sodium trimethoxy borohydride; organic tin hydrides, for example, tributyltin hydride, dibutyltin hydride, diethyltin hydride or triphenyl tin hydride in the presence of radical initiator (e.g., azobisisobutyronitrile or benzoylperoxide); or alkali metal aluminum hydrides, for example, lithium aluminum hydride or sodium aluminum hydride.
  • metal catalysts being, for example, palladium- carbon, palladium black, Raney-nickel, platinum black or platinum dioxide
  • metal hydride complexes for example, sodium borohydride, potassium borohydride,
  • Suitable solvents include, for example, organic solvents that are inert under reaction conditions.
  • solvents include water; alcohols, for example, methanol, ethanol, isopropanol or butanol; ketones, for example, acetone or methyl isobutyl ketone; ethers, for example, diethylether, diisopropylether or dimethoxyethane; nitriles, for example, acetonitrile; chlorinated hydrocarbons, for example, methylene chloride, ethylenedichloride or carbon tetrachloride; esters, for example, ethylacetate or isopropylacetate; dipolar aprotic solvents, for example, dimethylsulfoxide or dimethylformamide; cyclic ethers, for example, dioxane or tetrahydrofuran; or mixtures thereof.
  • the temperatures at which the reactions of the processes provided herein may be carried out are not critical. For example, such reactions can be performed at temperatures from about 20 °C to about 120 °C. In other embodiments, the reactions can be performed at temperatures from about 25 °C to 50 °C. Pressure significantly affects the dehalogenation reaction carried out in the presence of metal catalyst in the presence of hydrogen. Catalytic hydrogenation at pressures less than 4.0 kg/cm 2 lead to the formation of the corresponding mono halogenated product and/or mixture of deprotected products.
  • catalytic hydrogenation carried out at pressures of about 2.5 or 3.5 kg/cm typically gives an HPLC output purity of between about 60-75 % for (lS)-(l(OH),2,4/l,3)-2,3,4-tri-O-benzyl-5- oxo-l-C-[benzyloxymethyl]-l,2,3,4-cyclohexanetetrol; 15-19 % for debenzylated side products and between about 1-7 % monochloro product.
  • catalytic hydrogenation carried out at a pressure of 4.50 kg/cm 2 typically gives an HPLC output purity of between about 94 % for (lS)-(l(OH),2,4/l,3)-2,3,4-tri-O-benzyl-5-oxo-l-C- [benzyloxymethyl]-l,2,3,4-cyclohexanetetrol; less than 1 % for debenzylated side products and less than about 2 % monochloro product.
  • the mixture of deprotected compounds formed as a side product carries forward in the next step where the compound of Formula II is reacted with ammonium acetate to form compound of Formula I and tends to form a dimmer impurity which affects the isolation of the product, yield and purity of the final product.
  • the reaction may be carried out at about 4.0 to about 6.0 kg / cm in some particular embodiments.
  • the compound of Formula II may be converted to voglibose by reacting the compound of Formula II with 2-amino-l,3-propanediol in the presence of a reducing agent followed by deprotection in the event that R is a protecting group.
  • reaction with 2-amino-l,3-propanediol can be carried out in the presence of an acid.
  • the pH can be maintained in the range of from about 7.5 to about 8 in some particular embodiments.
  • compound of Formula II may be converted to compound of Formula I, for example, by methods disclosed in U.S. Patent No. 4,898,986; and J Org. Chem., 57:3642 (1992) which are incorporated herein by reference.
  • U.S. Patent No. 4,898,986 and J Org. Chem., 57:3642 (1992) disclose the conversion of the n-oxime of valiolone to valiolamine by reaction using Raney-nickel.
  • 4,824,943 discloses the conversion of valeinamine to valiolamine using a multistep synthetic route.
  • the compound of Formula I can be converted to voglibose by a process comprising the steps of reacting the compound of Formula I with dihydroxy acetone and a reducing agent, followed by deprotection in the event that R is a hydroxyl-protecting group. This reaction can be carried out in the presence of an acid, and in particular to maintain a pH in the range of from about 6 to about 6.5.
  • the compound of Formula I can be converted to voglibose by a process comprising deprotecting the compound of Formula I (in the event that R is a protecting group) to obtain valiolamine, followed by reaction of valiolamine with dihydroxy acetone and a reducing agent.
  • the above processes of converting a compound of Formula I to voglibose can be carried out in the same solvents as those listed above for reacting a compound of Formula II with ammonium acetate or ammonium formate.
  • the product obtained by the reaction of a protected compound of Formula I with dihydroxyacetone and by the reaction of a compound of Formula II with 2-amino-l,3- propanediol, wherein R is hydroxyl protecting group can be deprotected by conventional means or methods known in the art, include those described in U.S. Patent Nos. 4,824,943, 4,898,986; and J. Org. Chem., 57:3642 (1992), which are incorporated herein by reference.
  • the acetal- or ketal-type protecting groups can be removed by acid hydrolysis.
  • the acyl-type protecting group can be removed by alkali hydrolysis.
  • the hydrogenation can be carried out in the presence of an acid to maintain a pH below 3 in some particular embodiments. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are included within the scope of the present invention. In the following section embodiments are described by way of examples to illustrate the process of invention. However, these are not intended in any way to limit the scope of the present invention. Several variants of these examples would be evident to persons ordinarily skilled in the art.
  • Example 1 Synthesis of (lS)-(l(Off). 2.4 /1.3V2.3,4-tri-O-benzyl-5-oxo-l-C- benzyloxymethyll- 1 ,2,3,4-cyclohexanetetrol
  • (lS)-(l(OH),2,4/l,3)-2,3,4-tri-O-benzyl-6,6-dichloro-5-oxo-l-C- [benzyloxymethyl]-l,2,3,4-cyclohexanetetrol 7.0 kg, HPLC purity: 92.11%) in tetrahydrofuran (28 L) and methanol (70 L) was added sodium acetate (4.66 kg) and 10% Pd/C (4.2 kg) at room temperature.
  • the suspension was stirred for 8 - 10 hours at 23 - 25 °C at a hydrogen pressure of 4.5 ⁇ 0.2 kg/cm 2 .
  • the reaction mixture was filtered through HYFLOTM (celite) and the celite bed was washed with methanol and tetrahydrofuran mixture (1 :1, 5 L). The combined filtrate was concentrated under reduced pressure at 40 - 45 °C. Water (25 L) was then added to the concentrated residue and was extracted with ethyl acetate twice (20 L each). The ethyl acetate layer was concentrated under reduced pressure. Diisopropyl ether (7 L) was then added and the mixture was cooled to 10 - 15 °C, and stirred for 30 minutes. The product was filtered at 10 °C, washed with diisopropyl ether (2 L) and dried under reduced pressure at 30 - 35 °C.
  • Example 2 Synthesis of ( ⁇ S)-( OH). 2,4/l,3V2.3.4-tri-O-benzyl-5-oxo-l-C- [benzyloxymethyl '
  • (lS)-(l(OH),2,4/l,3)-2,3,4-tri-O-benzyl-6,6-dichloro-5-oxo-l-C- [benzyloxymethyl]-l,2,3,4-cyclohexanetetrol 7.0 kg, HPLC purity: 92.11%) in tetrahydrofuran (28 L) and methanol (70 L) was added sodium acetate (4.66 kg) and 10% Pd/C (4.2 kg) at room temperature.
  • the suspension was stirred for 8 - 10 hours at 23 - 25 °C at a hydrogen pressure of 4.5 ⁇ 0.2 kg/cm 2 .
  • the reaction mixture was filtered through HYFLOTM (celite) and the celite bed was washed with methanol and tetrahydrofuran mixture (1 : 1, 5 L). The combined filtrate was concentrated under reduced pressure at 40 - 45 °C. Water (25 L) was then added to the concentrated residue and extracted with ethyl acetate twice (20 L each). The ethyl acetate layer was concentrated under reduced pressure.
  • Example 3 Synthesis of flSV(l(OH),2,4/1.3V2.3,4-tri-O-benzyl-5-oxo-l-C- [benzyloxymethyl " j-l,2,3,4-cvclohexanetetrol
  • (lS)-(l(OH),2,4/l,3)-2,3,4-tri-O-benzyl-6,6-dichloro-5-oxo-l-C- [benzyloxymethyl]-l,2,3,4-cyclohexanetetrol (15 g, 24.15 mmol) in methanol and tetrahydrofuran (2.5 : 1, 190 mL) were added 10% palladium carbon (7 g), sodium acetate (7.0 g, 85.33 mmol) and water (4 mL), and the mixture was hydrogenated with shaking for 6 hours at 3.5 to 4.0 kg/cm 2 pressure at room temperature.
  • Example 6 Synthesis of ( lS ) - ( l ( OH ⁇ 2A5/1.3V5amino-l-C-hvdroxymethyl-1.2,3A cyclohexanetetrol
  • (lS)-(l(OH),2,4,5/l,3)-2,3,4-tri-O-benzyl-5-amino-l-C- [benzyloxymethyl]-l,2,3,4-cyclohexanetetrol (2.26 g, 4.1 mmol) in mixtures of methanol and tetrahydrofuran (1:1, 50 mL) were added 10% palladium carbon (1.4 g) and 4% hydrochloric acid solution (16.5 mL).
  • the mixture was hydrogenated with shaking for 4.5 hours at 2.5-3.0 kg/cm 2 at 40 °C.
  • the reaction mixture was filtered and washed with methanol.
  • the combined filtrate was concentrated and the resulted residue was chromatographed using ion exchange resin (Indion 225 H+) to give the title compound.
  • Example 7 Synthesis of ⁇ sy(l(OH A5/ -2 Atri-O-benzyl-5-IT2-hvdroxy-l- (hydroxymethyl) ethyl! amino]-l-C-rbenzylox ethyl ⁇
  • Example 9 Synthesis of (lS)-(l(OH ⁇ 2.4.5/1.3V2.3.4-tri-O-benzyl-5-rr2-hvdroxy-l- (hvdroxymethv ⁇ ethyllaminol-l-C-rbenzyloxymethyll-l,2,3,4-cvclohexanetetrol 2-amino-l,3-propanediol (20.
  • Example 10 Synthesis of (lS>n(OH),2A5/ V5-rr2-hvdroxy-l-(hvdroxymethyl) ethyl1aminol-l-C-(hvdroxymethyl)- 2,3,4-cvclohexanetetrol (Voglibose) To a solution of (lS)-(l(OH),2,4,5/l,3)-2,3,4-tri-O-benzyl-5-[[2-hydroxy-l- (hydroxymethyl)ethyl]amino]-l-C-[benzyloxymethyl]-l,2,3,4-cyclohexanetetrol (13.0 g, 20.73 mmol) in methanoktetrahydrofuran (1:1, 260 mL) were added 10 % palladium- carbon (13 g) and 4% hydrochloric acid solution (20 mL), and the mixture was hydrogenated with shaking for 3 hours at 3.0 - 3.5 kg/cm at room temperature

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Abstract

L'invention concerne des procédés pour la préparation de dérivés de 1,2,3,4-cyclohexanetétrol, lesquels sont des intermédiaires utiles pour la synthèse de voglibose; des procédés pour la préparation de 2,3,4,5-tétrahydroxycyclohexanone substituée; et des procédés pour la préparation de voglibose. Sont également décrits des composés obtenus à l'aide desdits procédés.
PCT/IB2004/003782 2003-11-21 2004-11-18 Procede pour la preparation de derives de 1,2,3,4-cyclohexanetetrol Ceased WO2005049547A1 (fr)

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Cited By (9)

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WO2008011791A1 (fr) * 2006-07-17 2008-01-31 Pharmaxyn Laboratories Ltd. Voglibose tetrabenzyle cristallin et procédé de préparation associé
CN103145650A (zh) * 2013-03-15 2013-06-12 浙江医药股份有限公司新昌制药厂 一种(-)-有效霉烯胺五乙酸酯环氧化物的制备方法
CN103254094A (zh) * 2013-03-15 2013-08-21 浙江医药股份有限公司新昌制药厂 一种(-)-有效霉醇胺五乙酸酯的合成方法
CN104098458A (zh) * 2014-08-07 2014-10-15 重庆植恩药业有限公司 一种伏格列波糖中间体的制备方法
CN105601485A (zh) * 2015-11-11 2016-05-25 重庆植恩药业有限公司 一种伏格列波糖中间体的制备方法
CN110317142A (zh) * 2019-07-18 2019-10-11 重庆植恩药业有限公司 一种伏格列波糖的制备方法
CN111748000A (zh) * 2019-03-29 2020-10-09 沈阳药科大学 3-脱氧-5-羟基-1-氨基碳糖类化合物及其用途
CN112479917A (zh) * 2020-12-10 2021-03-12 山东国邦药业有限公司 一种美他环素的制备方法
CN115340465A (zh) * 2022-10-20 2022-11-15 中孚药业股份有限公司 一种伏格列波糖的合成方法

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KR101379988B1 (ko) 2006-07-17 2014-04-01 파마신 라보라토리스 엘티디. 결정상의 테트라벤질 보글리보스 및 그의 제조방법
WO2008011791A1 (fr) * 2006-07-17 2008-01-31 Pharmaxyn Laboratories Ltd. Voglibose tetrabenzyle cristallin et procédé de préparation associé
CN103145650B (zh) * 2013-03-15 2016-03-23 浙江医药股份有限公司新昌制药厂 一种(-)-有效霉烯胺五乙酸酯环氧化物的制备方法
CN103254094A (zh) * 2013-03-15 2013-08-21 浙江医药股份有限公司新昌制药厂 一种(-)-有效霉醇胺五乙酸酯的合成方法
CN103254094B (zh) * 2013-03-15 2015-08-19 浙江医药股份有限公司新昌制药厂 一种(-)-有效霉醇胺五乙酸酯的合成方法
CN103145650A (zh) * 2013-03-15 2013-06-12 浙江医药股份有限公司新昌制药厂 一种(-)-有效霉烯胺五乙酸酯环氧化物的制备方法
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CN105601485A (zh) * 2015-11-11 2016-05-25 重庆植恩药业有限公司 一种伏格列波糖中间体的制备方法
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CN110317142A (zh) * 2019-07-18 2019-10-11 重庆植恩药业有限公司 一种伏格列波糖的制备方法
CN110317142B (zh) * 2019-07-18 2023-03-28 植恩生物技术股份有限公司 一种伏格列波糖的制备方法
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