WO2011106546A1 - Procédé pour la préparation d'un intermédiaire de la rosuvastatine - Google Patents

Procédé pour la préparation d'un intermédiaire de la rosuvastatine Download PDF

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Publication number
WO2011106546A1
WO2011106546A1 PCT/US2011/026104 US2011026104W WO2011106546A1 WO 2011106546 A1 WO2011106546 A1 WO 2011106546A1 US 2011026104 W US2011026104 W US 2011026104W WO 2011106546 A1 WO2011106546 A1 WO 2011106546A1
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WO
WIPO (PCT)
Prior art keywords
mono
ester compound
solvent
methyl
cal
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PCT/US2011/026104
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English (en)
Inventor
Tihamer Paal
Laszlo Toth
Valerie Niddam-Hildesheim
Brijnath P. Chaurasia
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Teva Pharmaceutical Industries Ltd.
Teva Pharmaceuticals Usa, Inc.
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Publication of WO2011106546A1 publication Critical patent/WO2011106546A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/62—Carboxylic acid esters
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
    • C12P41/005—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of carboxylic acid groups in the enantiomers or the inverse reaction

Definitions

  • the present invention encompasses a process for desymmetrization of a prochiral di- ester compound to prepare the corresponding optically enriched (S)-mono-ester, one example of which is (S)-methyl 3-hydroxyglutarate, an intermediate of rosuvastatin.
  • Rosuvastatin (7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonyl- amino) pyrimidin-5-yl]-(3R, 5S)-dihydroxy-(E)-6-heptenoic acid) calcium, having the following chemical formula:
  • Rosuvastatin calcium is an HMG-CoA reductase inhibitor.
  • the present invention provides an enzyme-catalyzed process for desymmetrization of a prochiral di-ester compound to prepare the corresponding optically enriched (S)-mono- ester.
  • the process of the invention can be applied to preparing enantio-enriched (S)-methyl 3-hydroxyglutarate, an intermediate in the synthesis of rosuvastatin, in high optical purity and yield.
  • the invention provides a process for desymmetrization of a prochiral di-ester compound of formula I:
  • R is a C1-C4 alkyl group
  • Ri is a hydrogen
  • a C1-C4 acyl preferably acetyl, propanoyl or butyryl
  • C1-C6 alkyl group preferably methyl or ethyl
  • n is 1, 2 or 3
  • R is a C1 -C4 alkyl group
  • Ri is a hydrogen
  • a C1 -C4 acyl preferably acetyl, propanoyl or butyryl
  • Ci-C 6 alkyl group preferably, methyl or ethyl
  • n is 1, 2 or 3
  • greater than 90% of the mono-ester is the (S)-mono-ester compound according to formula II, and less than 10% of the mono-ester is present as the corresponding (R)-mono-ester as assessed by HPLC
  • CAL- B at a pH from about 5 to about 8, preferably from about 5 to about 6.5, to obtain the mono- ester compound according to formula IIA, wherein greater than 99% of the mono-ester compound is the (S)-mono-ester according to formula II; and less than 1% of the mono-ester is present as the corresponding (R)-mono-est
  • the product obtained by the above described processes contains optically pure mono-ester according to formula IIA, which is greater than 99.5% (S)-mono-ester and less than 0.5% (R)-mono-ester by HPLC. According to other embodiments, the product obtained contains optically pure mono-ester according to formula IIA, which is greater than 99.85% (S)-mono-ester and less than 0.15% (R)-mono-ester by HPLC.
  • the invention provides a process for preparing optically pure (S)-methyl-hydroxyglutarate comprising: (a) combining dimethyl 3-hydroxy- glutarate and Candida Antarctica lipase B ("CAL-B") or Candida Antarctica lipase A
  • CAL-A to obtain a reaction mixture containing methyl 3-hydroxyglutarate wherein greater than 90% by HPLC of the methyl 3-hydroxyglutarate is (S)-methyl 3-hydroxyglutarate, and less than 10% by HPLC of the mono-ester is present as the corresponding (R)- methyl 3-hydroxyglutarate; and (b) further reacting the reaction mixture formed in step (a) with CAL-B at a pH from about 5 to about 8, or about 5 to about 6.5, to obtain a product that contains optically pure (S)-methyl 3-hydroxyglutarate which is greater than 99% (S)-methyl 3-hydroxyglutarate and less than 1% (R)-methyl 3-hydroxyglutarate by HPLC.
  • the product obtained contains optically pure (S)-methyl 3- hydroxyglutarate which is greater than 99.5% (S)-methyl 3-hydroxyglutarate and less than 0.5% (R)-methyl 3-hydroxyglutarate acid by HPLC. According to other embodiments, the product obtained contains optically pure (S)-methyl 3-hydroxyglutarate which is greater than 99.85% (S)-methyl 3-hydroxyglutarate and less than 0.15% (R)-methyl 3-hydroxyglutarate by HPLC.
  • the present invention provides a process for preparing rosuvastatin or a pharmaceutically acceptable salt thereof comprising prepaiing (S)-methyl 3- hydroxyglutarate by the process of the present invention; and converting it to Rosuvastatin or a pharmaceutically acceptable slat thereof, preferably Rosuvastatin Calcium.
  • Figure 1 HPLC pattern of a sample obtained after the desymmetrization process (stereoselective hydrolysis followed by a ldnetic resolution).
  • Figure 2 HPLC pattern of a sample obtained after stereo-selective hydrolysis.
  • the present invention encompasses a process for desymmetrization of a prochiral di- ester compound to prepare the corresponding optically enriched (S)-mono-ester, one example of which is (S)-methyl 3 -hydroxyglutarate, an intermediate of Rosuvastatin.
  • optically pure refers to compounds having an optical purity of above at least about 99%, as measured by HPLC.
  • the HPLC purity is determined by the area under the peaks observed after separation on an analytical chiral column, followed by detection using a UN detector at a wavelength of 220 nm or mass spectrometric (MS) detection.
  • the chiral column contains a silica support coated with a polysaccharide chiral stationary phase.
  • the column is a Chiralpack AD-H analytical column, preferably of dimensions 250 mm (length) x 4.6 mm (internal diameter), 5 microns (particle size) (Daicel Chemical Industries Ltd).
  • the eluent is methanol: water rformic acid, preferably in a ratio of 80:20:0.1.
  • the flow rate is about 0.20 ml/min.
  • Preferred HPLC and MS detection parameters conditions are set out in the examples.
  • the CAL-A used in the examples herein was purchased from Codexis.
  • the CAL-A used in the examples herein was purchased from Codexis or from Novozymes.
  • the present invention provides a process, wherein prochiral diesters of dicarboxylic acids are first hydrolyzed by an enzyme-catalyzed enantio-selective process, and then are enantiomerically emiched by a kinetic resolution enzymatic process. The hydrolysis and the kinetic resolution can be done by the same enzyme, and the process may be a one-pot process.
  • the process comprises: combining substrate prochiral diester of a dicarboxylic acid and Candida Antarctica lipase B ("CAL-B”) or Candida Antarctica lipase A (“CAL-A”) to obtain a reaction mixture, maintaining the reaction mixture for a time sufficient to produce a mono-ester according to formula IIA:
  • R is a C C alkyl group and 3 ⁇ 4 is a hydrogen; a C r C 4 acyl, preferably acetyl, propanoyl, or butyryl; or a Ci-C 6 alkyl group, preferably methyl or ethyl; and n is 1, 2 or 3; and wherein greater than 90% of the product mono-ester in the reaction mixture is the (S)-mono-ester according to formula II:
  • R is a C1-C4 alkyl group
  • 3 ⁇ 4 is a hydrogen, a C1-C4 acyl, preferably acetyl, propanoyl, or butyryl; or a Ci-C 6 alkyl group, preferably methyl or ethyl
  • n is 1, 2 or 3; and less than 10% of the mono-ester is present as the corresponding (R)-mono-ester, as assessed by HPLC;
  • step (b) further reacting the reaction mixture formed in step (a) with CAL-B at a pH from about 5 to about 8, preferably from about 5 to about 6.5; to obtain the mono-ester according to formula IIA, wherein greater than 99% of the mono-ester is the (S)-mono-ester according to formula II, and less than 1% of the mono-ester is present as the corresponding (R)-mono- ester, as assessed by HPLC.
  • the process of the invention can be used to prepare optically pure (S)-methyl 3 -hydroxyglutarate which is greater than 99% (S)-methyl 3- hydroxyglutarate and less than 1% (R)-methyl 3 -hydroxyglutarate by HPLC.
  • the (S)-methyl 3 -hydroxyglutarate product according to the claimed process contains optically pure (S)-methyl 3 -hydroxyglutarate which is greater than 99.5% or greater than 99.85% (S)-methyl 3 -hydroxyglutarate and less than 0.5%, or less than 0.15%, respectively of the corresponding (R)-methyl 3 -hydroxyglutarate by HPLC.
  • the process includes two steps: a) stereo-selective hydrolysis of a substrate prochiral diester of a dicarboxylic acid to obtain an enriched mono-ester according to formula IIA, which contains greater than 90% of the (S) enantiomer by HPLC and less than 10% of the corresponding (R)-enantiomer by HPLC; and b) kinetic resolution of (R)-enantiomer
  • step a) to obtain the mono-ester according to formula IIA, wherein greater than 99% of the mono-ester is the (S)-mono-ester according to formula II, and less than 1% of the mono-ester is present as the corresponding (R)-mono-ester by HPLC.
  • the process may be illustrated by the following scheme:
  • R is a Cj-C 4 all yl group
  • R] is a hydrogen, a C1-C4 acyl, preferably acetyl, propanoyl, or butyryl; or a C i-C 6 alkyl group, preferably methyl or ethyl; and n is 1, 2 or 3.
  • the stereo-selective hydrolysis in step (a) is typically done in the presence of water or an aqueous solvent.
  • the aqueous solvent comprises water and may further comprise one or more suitable co-solvents.
  • Suitable co-solvents include for example Cj-C 4 alcohols, such as methanol, ethanol, propanol, isopropanol and butanol; C 3 -C 7 ketones, such as acetone and methylethylketone (MEK); C 4 -C 6 ethers, such as diethyl ether, methyl-t-butyl ether, tetraliydrofuran and dioxane; C 5 -C] 0 hydrocarbons, such as pentane, hexane, and cyclohexane; Ci-C 6 halogenated hydrocarbons, such as methylene chloride, chloroform, and 1,1,1-trichloroethane; C 2 -C 6 nitriles, such as acetonitrile and propionitrile; C 2 -C 7 amides, such as dimethylformamide and dimethylacetamide, and dimethyl sulfoxide. Preferred solvents are
  • an alcoholic solvent is used, it is preferably used in amount of up to about 5% (v/v).
  • the aqueous solvent may further contain a suitable buffer.
  • suitable buffers include, for example, triethanolamine-HCl buffer, triethanolamine-H 2 S0 4 buffer and KH2PO4 E 2HPO4 buffer.
  • enzymes are used in a combination with a buffer.
  • the buffer provides a pH suitable for the enzyme activity.
  • a suitable pH for CAL-B and CAL-A activity is from about 3.5 to about 10, or from about 5 to about 8.5.
  • step (a) is done a t pH of about 6 to about 8.5, preferably about 7.5.
  • a suitable base is added to the reaction mixture during the reaction to control the pH of the reaction mixture.
  • Suitable bases include alkali metal hydroxides, such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides, such as calcium hydroxide and magnesium hydroxide; ammonium hydroxides, and alkali metal carbonates, such as such as sodium or potassium carbonate; hydrogen carbonates, such as sodium or potassium bicarbonate alkaline earth metal carbonates, such as calcium carbonate; and ammonium carbonates; or organic bases such as C]-C 6 primary amines, e.g., methyl amine or ethyl amine, C2-C 8 secondary amines, e.g., dimethyl amine, diethyl amine, piperidine, C 3 -C 10 tertiary amines, e.g., trimethyl amine, triethylamine, and diisopropylethylamine, guanidine, heterocyclic amines, e.g.
  • the substrate prochiral diester of a dicarboxylic acid e.g., dimethyl 3- hydroxyglutarate
  • the enzyme CAL-B or CAL-A
  • Suitable temperatures for this enzymatic reaction are, for example from about -5°C to about 20°C, or from about 0°C to about 15°C, or about 5°C.
  • the reaction mixture containing the substrate prochiral diester of a dicarboxylic acid (e.g., dimethyl 3 -hydroxy glutarate), the CAL-B or CAL-A and optionally the co-solvent is maintained, for example, at a temperature of about -5°C to about 20°C, or from about 0°C to about 15°C, or about 5°C, for a time from about 90 minutes to about 10 hours, or from about 4 hours to about 5 hours to obtain an enriched mono-ester according to formula IIA, which contains greater than 90% of the (S) enantiomer by HPLC and less than 10% of the corresponding (R)-enantiomer by HPLC, e.g., a mixture that is greater than 90% of (S)- methyl-hydroxyglutarate and less than 10% of (R)-methyl-hydroxyglutarate.
  • a dicarboxylic acid e.g., dimethyl 3 -hydroxy glutarate
  • CAL-B or CAL-A e.g.
  • the enriched (S)-mono-ester e.g., (S)-methyl-hydroxyglutarate can be obtained in an optical purity of about 95% to about 99% by HPLC, while the corresponding (R)-enantiomer of the product mono-ester, e.g., (R)-methyl-hydroxyglutarate can be obtained in an optical purity of about 5% to about 1% by HPLC.
  • the stereoselective hydrolysis can lead to the formation of an alcohol, e.g., methanol, ethanol, propanol or isopropanol corresponding to the C]-C 4 alkyl group on the substrate diester.
  • an alcohol e.g., methanol, ethanol, propanol or isopropanol corresponding to the C]-C 4 alkyl group on the substrate diester.
  • that alcohol can be removed prior to the kinetic resolution portion of the process.
  • the alcohol by-product R-OH formed in step (a) is removed after step (a) in any of the above embodiments of the process of the invention.
  • step (b) involves the addition of CAL-B after the removal of the alcohol by-product
  • the reaction in step b) is typically done while adjusting the pH to about 5 to about 8, preferably to about 5 to about 6.5, more preferably to about 6.5; and adding additional amount of CAL-B, or adding by CAL-A.
  • the amount of CAL-A or CAL-B added in step (b) is about 1.5 to about 2 times of the amount of CAL-B used in step (a).
  • step (b) The addition of the enzyme (CAL-B or CAL-A) and the reaction in step (b) is carried out at a suitable pH to form the reaction mixture for the second step of the process.
  • the suitable pH is from about 5 to about 8, preferably to about 5 to about 6.5, more preferably, about 6.5.
  • This reaction mixture can be maintained, for example, at a temperature of about -5°C to about 20°C, or about 5°C, for about 1 day to about
  • optically pure (S)-mono-ester e.g., (S)-methyl-hydroxyglutarate, i.e., the (S)-mono-ester having an optical purity greater than about 99%, or greater than about 99.5%, or greater than about 99.85% by HPLC.
  • the obtained optically pure (S)-mono-ester e.g., (S)-methyl-hydroxyglutarate may be recovered from the reaction mixture that also contains the corresponding symmetric diacid, e.g., 3-hydroxy glutaric acid.
  • the recovery may be done for example by extraction from ethyl acetate/ethanol at suitable pH, for example, a pH of about 2.0 to about 3.5, or a pH of about
  • Optically pure (S)-methyl-hydroxyglutarate obtained as a product of the claimed process may be used to prepare rosuvastatin.
  • Flow rate and temperature in the HPLC conditions may be slightly varied in order to achieve the required system suitability.
  • the mass spectrometric parameters may be varied in order to obtain the desired sensitivity.
  • Lipozyme CAL-B L (10.0 g, Novozymes, > 5000 U/g specific activity) was added to the mixture with vigorous stirring. The stirring was maintained with cooling to 5°C.
  • the pH was kept constant at 7.5 with KOH (4.0 M aqueous), with the aid of a pH-stat (during 4 h of desymmetrization 285 ml of KOH 4.0 M was consumed).
  • the methanol formed during the stereo-selective hydrolysis, and the water, was partially evaporated from the reaction mixture (evaporation to 50% of the initial volume) under vacuum, at 20 °C. Then the mixture was diluted back to the initial volume (1130 ml) with distilled water. The pH of the thus-formed mixture was adjusted to 6.5 with a few ml of HCl (36%) and Lipozyme CAL-B L (17.43 g) was added. The resulting reaction mixture was maintained at pH 6.5 (controlled by pH-stat) at 20°C for 36 h.
  • the volume of the reaction mixture was reduced twice (after 36 h and 60 h of enantioenrichment) during the reaction by applying vacuum (7-20mbar) at 20°C, the evaporated volume was replaced with an equivalent volume of ice-cooled distilled water.
  • the reaction mixture was stirred at 20°C between the evaporations and at 5°C after the last evaporation.
  • Triethanolamine-sulfate buffer made from 2.98 g of triethanolamine, corresponding to 0.1 M triethanolamine in the final reaction mixture.
  • Triethanolamine was dissolved in distilled water, the pH was adjusted using H 2 S0 4 , the volume was adjusted to 200 ml with H 2 0, the pH to 7.5.
  • Lipozyme CAL-B L (2.41 g, Novozymes, > 5000 U/g specific activity) was added to the mixture cooled to 5°C, in a glass reactor. The stirring was maintained under cooling, the pH was kept constant with K 2 C0 3 (3.0 M, aqueous), with the aid of a pH-stat, for 5 h. During the last hour the pH was let to drop until 6.5.

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Abstract

La présente invention a pour objet des procédés utilisant un traitement à la lipase B de Candida Antarctica (« CAL-B ») ou à la lipase A de Candida Antarctica (« CAL-A ») pour la désymétrisation d'un composé di-ester prochiral de formule (I) : dans laquelle R est un groupe alkyle en C1 à C4, R1 est un atome d'hydrogène ; un acyle en C1 à C4, de préférence un acétyle, un propanoyle ou un butyryle ; ou un groupe alkyle en C1 à C6, de préférence un méthyle ou un éthyle, et n est 1, 2 ou 3, pour préparer le (S)-mono-ester optiquement pur correspondant selon la formule (II).
PCT/US2011/026104 2010-02-25 2011-02-24 Procédé pour la préparation d'un intermédiaire de la rosuvastatine WO2011106546A1 (fr)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103834705A (zh) * 2014-03-24 2014-06-04 山东齐都药业有限公司 高纯度匹伐他汀钙的制备方法
EP2778229A1 (fr) * 2013-03-11 2014-09-17 Sandoz Ag Procédé de fabrication énantiosélective de monoesters d'acide 3-hydroxyglutarique et leur utilisation
CN105121661A (zh) * 2013-02-01 2015-12-02 加利福尼亚大学董事会 用于基因组组装及单体型定相的方法
CN106676141A (zh) * 2015-11-06 2017-05-17 浙江京新药业股份有限公司 手性中间体(s)-3-羟基戊二酸单酯的酶法制备方法
US10131889B1 (en) * 2017-07-14 2018-11-20 Jiangnan University Candida antarctica lipase B mutant, and methods for making and using the same

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003087112A1 (fr) 2002-04-09 2003-10-23 Cls Laboratories, Inc. Intermediaire chiral et son procede de production
WO2008130638A2 (fr) * 2007-04-18 2008-10-30 Teva Pharmaceutical Industries Ltd. Procédé de préparation d'intermédiaires d'inhibiteurs des hmg-coa réductases

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003087112A1 (fr) 2002-04-09 2003-10-23 Cls Laboratories, Inc. Intermediaire chiral et son procede de production
WO2008130638A2 (fr) * 2007-04-18 2008-10-30 Teva Pharmaceutical Industries Ltd. Procédé de préparation d'intermédiaires d'inhibiteurs des hmg-coa réductases

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
ANDERS RIISE MOEN ET AL: "Absolute configurations of monoesters produced by enzyme catalysed hydrolysis of diethyl 3-hydroxyglutarate", TETRAHEDRON : ASYMMETRY, vol. 15, 2004, pages 1551 - 1554, XP002648571 *
CURR. ORG. SYNTH., vol. 6, 2009, pages 362 - 379
ELISABETH EGHOLM JACOBSEN ET AL: "Enantioselective enzymatic preparation of chiral glutaric monocarboxylic acids and amides", JOURNAL OF MOLECULAR CATALYSIS B: ENZYMATIC, vol. 21, 2003, pages 55 - 58, XP002648570 *
J ORG. CHEM., vol. 49, 1984, pages 3657 - 3659
J ORG. CHEM., vol. 61, no. 17, 1996, pages 6024 - 6027
J ORG. CHEM., vol. 64, 1999, pages 1464 - 1470
SYNTHETIC COMMUNICATIONS, vol. 20, no. 3, 1990, pages 315 - 319
TETRAHEDRON ASYMMETRY, vol. 15, 2004, pages 1551 - 1554
TETRAHEDRON LETTERS, vol. 48, 2007, pages 6873 - 6876
TRODLER ET AL: "Rational design of a new one-step purification strategy for Candida antarctica lipase B by ion-exchange chromatography", JOURNAL OF CHROMATOGRAPHY, ELSEVIER SCIENCE PUBLISHERS B.V, NL, vol. 1179, no. 2, 21 December 2007 (2007-12-21), pages 161 - 167, XP022413336, ISSN: 0021-9673 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105121661A (zh) * 2013-02-01 2015-12-02 加利福尼亚大学董事会 用于基因组组装及单体型定相的方法
EP2778229A1 (fr) * 2013-03-11 2014-09-17 Sandoz Ag Procédé de fabrication énantiosélective de monoesters d'acide 3-hydroxyglutarique et leur utilisation
WO2014140006A1 (fr) * 2013-03-11 2014-09-18 Sandoz Ag Procédé de synthèse énantiosélective de monoesters de l'acide 3-hydroxy-glutarique et utilisation
CN103834705A (zh) * 2014-03-24 2014-06-04 山东齐都药业有限公司 高纯度匹伐他汀钙的制备方法
CN106676141A (zh) * 2015-11-06 2017-05-17 浙江京新药业股份有限公司 手性中间体(s)-3-羟基戊二酸单酯的酶法制备方法
CN106676141B (zh) * 2015-11-06 2020-12-08 浙江京新药业股份有限公司 手性中间体(s)-3-羟基戊二酸单酯的酶法制备方法
US10131889B1 (en) * 2017-07-14 2018-11-20 Jiangnan University Candida antarctica lipase B mutant, and methods for making and using the same

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