WO2007078176A1 - The method of making optically active 2-chloromandelic acid esters and 2-chloromandelic acids by enzymatic method - Google Patents
The method of making optically active 2-chloromandelic acid esters and 2-chloromandelic acids by enzymatic method Download PDFInfo
- Publication number
- WO2007078176A1 WO2007078176A1 PCT/KR2007/000085 KR2007000085W WO2007078176A1 WO 2007078176 A1 WO2007078176 A1 WO 2007078176A1 KR 2007000085 W KR2007000085 W KR 2007000085W WO 2007078176 A1 WO2007078176 A1 WO 2007078176A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- optically active
- chloromandelic
- chloromandelic acid
- acid esters
- acids
- Prior art date
Links
Classifications
-
- 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
-
- 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
- C12P7/02—Preparation of oxygen-containing organic compounds containing a hydroxy group
- C12P7/22—Preparation of oxygen-containing organic compounds containing a hydroxy group aromatic
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/822—Microorganisms using bacteria or actinomycetales
- Y10S435/832—Bacillus
- Y10S435/839—Bacillus subtilis
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/911—Microorganisms using fungi
- Y10S435/913—Aspergillus
- Y10S435/918—Aspergillus oryzae
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/911—Microorganisms using fungi
- Y10S435/921—Candida
Definitions
- the present invention relates to process for the preparation of optically active
- optically active 2-chloromandelic acid ester represented by the general formula 2 and optically active 2-chloromandelic acid represented by the general formula 3 are prepared from racemic 2-chloromandelic acid ester represented by the general formula 1 in scheme 1 by hydrolases or hydrolase-producing microorganisms.
- R is selected from substituted or unsubstituted alkyl groups or alkenyl groups wherein the alkyl contains from C i to C , benzyl groups, cycloalkyl groups comprising from C 3 to C 6 , substituted or unsubstituted arylalkyl groups, and substituted or unsubstituted heteroarylalkyl groups.
- Optically active 2-chloromandelic acid esters are valuable chiral intermediates for synthesizing (S)-clopidogrel bisulfate with platelet aggregation inhibiting activity.
- Tosylated or mesylated compounds can be converted to optically active 2-chlorostyrene oxide which is used for important pharmaceutical intermediates by epoxydation (Korea Patent 10-2005-0035057).
- Noda Hirobumi et al.(JP-0072644) prepared a diastereomer salt by reacting racemic 2-chloromandelic acid with an optically active N-benzyl-1-phenylethylamine as an optical resolution agent and obtained (R)-2-chloromandelic acid by acidification of a diastereomer salt.
- this method needs recrystallization process.
- Hyoda Toshiharu et al.(JP-0114737) obtained (R)-2-choloromandelic acid using optically active alanine as an optical resolution agent.
- the present invention provides the new method of preparing of optically active 2-chloromandelic acid esters and their acids by hydrolases or hydrolase-producing microorganisms. And this method can be used in practical process because seperation and recovery of 2-chloromandelic acid esters and their acids produced by this invention are easier.
- this invention includes the process for preparing optically active 2-chloromandelic acid ester and optically active 2-chloromandelic acid by stereospecific hydrolysis of racemic 2-chloromandelic acid ester using hydrolases or hydrolase-producing mi- croorganisms. And optically active 2-chloromandelic acid ester is converted to optically active 2-chloromandelic acid by hydrolysis using agents such as sodium hydroxide.
- hydrolases such as CAL A(Novozym
- CAL B(Novozym 435), alcalase, and protease A or hydrolase-producing microorganisms are used as biocatalysts.
- Racemic 2-chloromandelic acid ester was determined using gas chromatography (Donam Instrument Inc., Model 6200) equipped with HP-FFAP column(Agilent, Inc., 3O m X 0.53 mm). The oven temperature was maintained initially at 100 0 C for 5 min and then raised at the rate of 20 °C/min to 220 0 C, and maintained for 10 min. Helium gas was used as carrier and column head pressure was maintained at 6 psi, and compounds were detected using FID at 220 0 C. In this condition, the typical retention time of methyl 2-chloromandelate, ethyl 2-chloromandelate and butyl 2-chloromandelic acid was 15.31 min, 14.89 min and 17.28 min, respectively.
- racemic 2-chloromandelic acid was added to 40ml of methanol and 35 % HCl solution. The reaction was carried out at 75 0 C for 3 hours. The reaction mixture was neutralized and racemic methyl 2-chloromandelate was gained by solvent extraction and distillation under reduced pressure. Racemic ethyl 2-chloromandelate and butyl 2-chloromandelate were synthesized using ethanol or buthanol, respectively instead of methanol. And the products were confirmed by nuclear magnetic resonance(Burker, Model DRS300).
- Example 2-3 Preparing of optically active methyl 2-chloromandelate by hydrolysis
- Racemic methyl 2-chloromandelate(l %(v/v)) prepared in Example 1 was added to 5 ml of 0.1 M potassium phosphate buffer(pH 7.0) and the reaction was carried out at 30 0 C using enzymes (1 %(w/v)). The reaction mixture was extracted with ethyl acetate and analyzed by above-mentioned method. The results are shown in Table 1.
- Example 4-7 Preparing of optically active ethyl 2-chloromandelate by hydrolysis [46] [47] Instead of racemic methyl 2-chloromandelate used in Example 2, ethyl 2-chloromandelate was used as a reactant and the results are shown in Table 2.
- Example 8 Preparing of optically active butyl 2-chloromandelate by hydrolysis [51] [52] Instead of racemic methyl 2-chloromandelate used in Example 2, butyl 2-chloromandelate was used as a reactant and CAL B was used as a biocatalyst. The reaction was carried out for 48 hours and butyl (R)-2-chloromandelate was obtained with 76 e.e% (conversion 93.1%).
- optically active 2-chloromandelic acid ester can be produced easily by this invention, and the product with high optical purity was obtained. Also, it is easy to recover optically active esters and optically active 2-chlromandelic acids after reaction. Therefore, this method is an useful process on the industrial scale.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Analytical Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020060001422A KR100722155B1 (ko) | 2006-01-05 | 2006-01-05 | 효소적 방법에 의한 광학활성 2-클로로만델릭산 에스테르와 2-클로로만델릭산의 제조 방법 |
KR10-2006-0001422 | 2006-01-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2007078176A1 true WO2007078176A1 (en) | 2007-07-12 |
Family
ID=38228460
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2007/000085 WO2007078176A1 (en) | 2006-01-05 | 2007-01-05 | The method of making optically active 2-chloromandelic acid esters and 2-chloromandelic acids by enzymatic method |
Country Status (2)
Country | Link |
---|---|
KR (1) | KR100722155B1 (ko) |
WO (1) | WO2007078176A1 (ko) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102206686A (zh) * | 2011-04-19 | 2011-10-05 | 华东理工大学 | 生物催化不对称还原制备(r)-邻氯扁桃酸甲酯的方法 |
CN108192932A (zh) * | 2017-12-26 | 2018-06-22 | 上海皓元生物医药科技有限公司 | 一种手性醇的酶催化制备方法 |
CN111118073A (zh) * | 2019-12-27 | 2020-05-08 | 东莞市东阳光生物合成药有限公司 | 酶法合成依米他韦中间体的方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5580765A (en) * | 1993-02-03 | 1996-12-03 | Nitto Chemical Industry Co., Ltd. | Process for producing optically active a-hydroxycarboxylic acid having phenyl group using gordona terrae |
JP2001072644A (ja) * | 1999-09-06 | 2001-03-21 | Yamakawa Yakuhin Kogyo Kk | 光学活性な2−クロロマンデル酸の製造方法および製造の中間体 |
JP2002114737A (ja) * | 2000-10-11 | 2002-04-16 | Japan Hydrazine Co Inc | 光学活性o−クロロマンデル酸の製造法 |
EP1382674A2 (en) * | 2002-07-16 | 2004-01-21 | Daicel Chemical Industries, Ltd. | Alpha-keto acid reductase, method for producing the same, and method for producing optically active alpha-hydroxy acids using the same |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100651338B1 (ko) * | 2003-01-06 | 2006-11-28 | 에스케이 주식회사 | 효모를 이용한 광학활성 (r)-2-클로로만델릭산 및 그에스테르 유도체의 제조방법 |
KR100752282B1 (ko) * | 2003-10-11 | 2007-08-29 | 주식회사 이큐스팜 | 효소를 이용한(r)-또는 (s)-폼의 2-클로로스틸렌옥사이드의 제조방법 |
-
2006
- 2006-01-05 KR KR1020060001422A patent/KR100722155B1/ko not_active IP Right Cessation
-
2007
- 2007-01-05 WO PCT/KR2007/000085 patent/WO2007078176A1/en active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5580765A (en) * | 1993-02-03 | 1996-12-03 | Nitto Chemical Industry Co., Ltd. | Process for producing optically active a-hydroxycarboxylic acid having phenyl group using gordona terrae |
JP2001072644A (ja) * | 1999-09-06 | 2001-03-21 | Yamakawa Yakuhin Kogyo Kk | 光学活性な2−クロロマンデル酸の製造方法および製造の中間体 |
JP2002114737A (ja) * | 2000-10-11 | 2002-04-16 | Japan Hydrazine Co Inc | 光学活性o−クロロマンデル酸の製造法 |
EP1382674A2 (en) * | 2002-07-16 | 2004-01-21 | Daicel Chemical Industries, Ltd. | Alpha-keto acid reductase, method for producing the same, and method for producing optically active alpha-hydroxy acids using the same |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102206686A (zh) * | 2011-04-19 | 2011-10-05 | 华东理工大学 | 生物催化不对称还原制备(r)-邻氯扁桃酸甲酯的方法 |
CN102206686B (zh) * | 2011-04-19 | 2013-06-26 | 华东理工大学 | 生物催化不对称还原制备(r)-邻氯扁桃酸甲酯的方法 |
CN108192932A (zh) * | 2017-12-26 | 2018-06-22 | 上海皓元生物医药科技有限公司 | 一种手性醇的酶催化制备方法 |
CN111118073A (zh) * | 2019-12-27 | 2020-05-08 | 东莞市东阳光生物合成药有限公司 | 酶法合成依米他韦中间体的方法 |
CN111118073B (zh) * | 2019-12-27 | 2022-02-15 | 宜昌东阳光生化制药有限公司 | 酶法合成依米他韦中间体的方法 |
Also Published As
Publication number | Publication date |
---|---|
KR100722155B1 (ko) | 2007-05-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPH0436195A (ja) | 光学活性α―ヒドロキシエステル類の製造方法 | |
WO2007078176A1 (en) | The method of making optically active 2-chloromandelic acid esters and 2-chloromandelic acids by enzymatic method | |
JP6169812B2 (ja) | リパーゼを利用してベータ−ラクトンからl−カルニチンを生産する方法 | |
EP2725012A1 (en) | 1-amino-2-vinyl cyclopropane carboxylic acid amide, salt of same, and method for producing same | |
JP4843812B2 (ja) | 酵素を使用するラセミα−置換ヘテロ環式カルボン酸の光学分割方法 | |
WO2007126258A1 (en) | The method of making optically active 2-halo-2-(n-substituted phenyl)acetic acid esters and 2-halo-2-(n-substituted phenyl)acetic acids by enzymatic method | |
US20020006644A1 (en) | Method for preparing an R- or S-form of alpha-substituted heterocyclic carboxylic acid and a counter enantiomeric form of alpha-substituted heterocyclic carboxylic acid ester thereto using enzyme | |
JP2002171994A (ja) | 光学活性なテトラヒドロフラン−2−カルボン酸またはその対掌体エステルの製造方法 | |
JP3704731B2 (ja) | 光学活性3−ヒドロキシヘキサン酸類の製造方法 | |
JP5506658B2 (ja) | 好熱性古細菌由来エステラーゼを用いた光学活性カルボン酸の製造方法 | |
KR100651338B1 (ko) | 효모를 이용한 광학활성 (r)-2-클로로만델릭산 및 그에스테르 유도체의 제조방법 | |
KR100758512B1 (ko) | 효소적 방법에 의한 광학활성3-히드록시-3-페닐프로피온산과 광학활성3-아실옥시-3-페닐프로피온산의 제조 방법 | |
JP3583798B2 (ja) | 光学活性2−メチルブタン酸およびその誘導体の製造方法 | |
KR100650798B1 (ko) | 광학활성 카복실산의 제조방법 | |
JPH1175889A (ja) | 光学活性α−トリフルオロメチル乳酸及びその対掌体エステルの製造方法及び精製方法 | |
EP2069516B1 (en) | Specific hydrolysis of the n-unprotected (r) -ester of (3 ) -amin0-3-arylpr0pi0nic acid esters | |
KR100545472B1 (ko) | 효소적 방법에 의한 광학활성 시스-1-r아미노-2-인다놀 및 그의 에스테르 제조방법 | |
JP2007117034A (ja) | 光学活性ニペコチン酸化合物の製造方法 | |
WO2007035066A1 (en) | The method of making optically active 3-acyloxy-gamma-butyrolactone and optically active 3-hydroxy-gamma-butyrolactone by enzymatic method | |
KR100650546B1 (ko) | 효소적 방법에 의한 광학활성 트랜스-1-알아미노-2-인다놀및 그의 에스테르 제조방법 | |
JPWO2004092113A1 (ja) | 光学活性2−アリルカルボン酸誘導体およびその製造法 | |
JP2007202563A (ja) | 光学活性α−トリフルオロメチル乳酸及びその対掌体エステルの製造方法及び精製方法 | |
KR20040071452A (ko) | 효소적 방법에 의한 광학활성 에틸 3-히드록시-3-페닐프로피오네이트 및 이의 에스테르 제조 방법 | |
JPH10248592A (ja) | 光学活性2−ベンジルコハク酸およびその誘導体の製法 | |
JP2008295302A (ja) | 光学活性エステル誘導体および/または光学活性カルボン酸の製造方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 07708437 Country of ref document: EP Kind code of ref document: A1 |