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WO1995033845A1 - Procede de production d'un compose d'alcool propargylique optiquement actif - Google Patents

Procede de production d'un compose d'alcool propargylique optiquement actif Download PDF

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Publication number
WO1995033845A1
WO1995033845A1 PCT/JP1995/001064 JP9501064W WO9533845A1 WO 1995033845 A1 WO1995033845 A1 WO 1995033845A1 JP 9501064 W JP9501064 W JP 9501064W WO 9533845 A1 WO9533845 A1 WO 9533845A1
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WO
WIPO (PCT)
Prior art keywords
group
carbon atoms
formula
optically active
alkyl group
Prior art date
Application number
PCT/JP1995/001064
Other languages
English (en)
Japanese (ja)
Inventor
Kazuya Kameo
Tohru Tanami
Hideo Tanaka
Yohichi Shimazaki
Masaru Mutoh
Mie Tsuboi
Naoya Ono
Katsuo Hatayama
Original Assignee
Taisho Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Taisho Pharmaceutical Co., Ltd. filed Critical Taisho Pharmaceutical Co., Ltd.
Priority to AU25752/95A priority Critical patent/AU2575295A/en
Publication of WO1995033845A1 publication Critical patent/WO1995033845A1/fr

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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
    • C12P41/004—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 alcohol- or thiol 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
    • C12P7/62—Carboxylic acid esters

Definitions

  • the present invention relates to an optically active propargyl alcohol compound and a method for producing an acylated product thereof.
  • optically active propargyl alcohol compounds and their acylated compounds are important as synthetic intermediates for various biologically active substances.
  • methods for producing optically active propargyl alcohol include (1) a method of optically reducing ketones (Gooding OW et al., J. Org. Chem., Vol. 58, p. 368, page 1). (2) Method for synthesis from 2,3-0-isopropylidene-slate (Niidas P. et al., Eesti NSV Tead Akad. Toim., Keem., Vol. 38 ( 4), pp. 285-6, 1989).
  • An object of the present invention is to provide a simpler method for producing an optically active propargyl alcohol compound having excellent optical purity and an acylated product thereof. Disclosure of the invention
  • the present inventors have conducted intensive studies for the purpose of solving the above-mentioned problems, and as a result, by stereoselectively acylating a racemic propargyl alcohol compound using an enzyme, a high purity and a high yield of the optically active compound are obtained.
  • the present inventors have found that a propargyl alcohol compound can be produced, and have completed the present invention.
  • R 1 and R 2 each represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms
  • R 3 represents a phenyl group, a ⁇ alkynol group having 1 to 5 carbon atoms, a halogen atom, a trifluoromethyl group
  • R 4 represents an alkyl group having 1 to 10 carbon atoms
  • the * symbol indicates that the compound is optically active.
  • a Lugyl alcohol compound is reacted in the presence of an enzyme with an acylating agent represented by the formula R 4 COOR (where R 4 has the same meaning as described above, and R represents any alkynole or alkenyl group).
  • R 4 has the same meaning as described above, and R represents any alkynole or alkenyl group.
  • a method for producing an optically active 0-acylpropargyl alcohol compound represented by the formula (1) characterized by comprising:
  • Another aspect of the present invention provides a method of formula (3), comprising separating an optically active 0-acylpropargyl alcohol compound of the formula (1) from the reaction solution after the above reaction, and hydrolyzing the compound.
  • Another aspect of the present invention is to provide an optically active compound, comprising separating an optically active pergyl alcohol compound having a steric configuration different from that of the compound of the formula (3) from the reaction solution after the reaction. This is a method for producing a propargyl alcohol compound.
  • the halogen atom is a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
  • the alkyl group having 1 to 3 carbon atoms is a chain or branched alkyl group, for example, a methyl group, an ethyl group, and an isopropyl group. Of these, a methyl group or an ethyl group is preferred.
  • the alkyl group having 1 to 5 carbon atoms is a chain or branched alkyl group, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a pentyl group, and an isopentyl group. .
  • An alkyl group having 1 to 8 carbon atoms is a chain or branched alkyl group, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, and the like.
  • An alkyl group having 1 to 10 carbon atoms is a chain or branched alkyl group, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a pentyl group, a Examples include a sopentyl group, a hexyl group, an isohexyl group, a heptyl group, and an isoheptyl group. Among them, preferred are a methyl group, an ethyl group, a propyl group, an isopropyl group and a butyl group.
  • Examples of the cycloalkyl group having 5 to 8 carbon atoms include a cyclopentyl group, a cyclohexyl group, a cycloheptyl group and the like.
  • the arbitrary alkyl group or alkenyl group represented by R may be any group which does not affect the reaction at all, for example, a methyl group, an ethyl group, a propynole group, an isopropyl group, a butyl group Group, isobutyl group, pentyl group, isopentyl group, hexyl group, isohexyl group, heptyl group, isoheptyl group, vinyl group, aryl group, 1-propenyl group, 2-buteninole group, isopropyl group And so on.
  • the enzyme used in the present invention refers to an optically active 0-acylpropargyl alcohol compound of the formula (1) formed from a (RS) -proparginole alcohol compound of the formula (2)
  • An enzyme having the activity of causing Preferred is an enzyme produced by a microorganism belonging to the genus Pseudomonas, and more preferred is lipase PS (Amano Pharmaceutical).
  • vinyl acetate, isopropenylpropionate, or isopropenylbenzoate can be used as the acylating agent, and is preferably isoprobenyl acetate.
  • Prono of the above formula (2) which is a raw material.
  • the racemic form of lugyl alcohol can be easily obtained, for example, by reacting the corresponding aldehyde form (4) with the acetylene Grignard reagent (5) as shown below (in the reaction formula, RR 2 and R 3 are as defined above, and X represents a bromo or chloro atom.
  • reaction with isopropenyl acetate is carried out by adding 0.1 to 50 times by weight of the enzyme and 1 to 50 parts by weight of the racemic propargyl alcohol of the formula (2).
  • the reaction is carried out in an inert solvent at 0 to 50 ° C. using 100 equivalents.
  • the inert solvent include methylene chloride, toluene, ether, t-butyl methyl ether and the like.
  • the reaction time varies considerably depending on the substrate, the reaction temperature and the amount of the enzyme, and varies from as little as one hour to several days, and is it possible to obtain the preferred isomer as an acetyl form? It is desirable to adjust as appropriate depending on whether the alcohol is obtained as unreacted alcohol. In the former case, it is preferable to keep the reaction rate at 50% or less, and in the latter case, conversely, when the reaction rate is raised to 50% or more, a compound with good optical purity can be obtained.
  • the obtained alcohol form was prepared according to the method of Niidas P. et al. (Eesti NSV Tead Akad. Toim., Keem., Volume 38 (4 ), Pp. 285-6, 1989), and confirmed to be S-form.
  • Example 2 The same operation as in (1) of Example 2 was performed using (3RS) —3-hydroxy-4,4-dimethyl-4-pentoxy-1-butyne obtained by the same method as in Example 1.
  • the present invention is useful as a simpler method for producing an optically active propargyl alcohol compound having a higher optical purity and an acylated product thereof.
  • optically active propargyl alcohol compounds and their acylated compounds are important as intermediates for the synthesis of various physiologically active substances, but are particularly important as intermediates for the synthesis of the ⁇ side chain of prostaglandin derivatives useful as pharmaceuticals. is there.

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  • 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)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un procédé permettant d'obtenir, de façon stéréosélective, un composé d'alcool O-acylpropargylique optiquement actif, représenté par la formule générale (2) (dans laquelle R1 et R2 représentent chacun hydrogène ou alkyle C¿1?-C3; R?3¿ représente phényle pouvant être substitué par alkyle C¿1?-C5, halogéno ou trifluorométhyle en une position arbitraire du noyau, alkyle C1-C8 ou cycloalkyle C5-C8; R?4¿ représente alkyle C¿1?-C10 ou phényle pouvant être substitué par phényle ou halogéno en une position arbitraire du noyau; et l'astérisque représente l'activité optique), ledit procédé consistant à faire réagir un composé d'alcool (RS)-propargylique représenté par la formule générale (1) (dans laquelle R?1, R2 et R3¿ correspondent à la définition donnée ci-dessus) avec un agent d'acylation correspondant à la formule R4COOR (où R4 correspond à la définition donnée ci-dessus et R représente un alkyle ou un alcényle arbitraire) en présence d'une enzyme. L'invention concerne également un procédé permettant d'obtenir un composé d'alcool propargylique optiquement actif soit par hydrolyse du composé O-acylique mentionné ci-dessus ou à partir de la solution résultant de la réaction d'acylation susmentionnée.
PCT/JP1995/001064 1994-06-02 1995-05-31 Procede de production d'un compose d'alcool propargylique optiquement actif WO1995033845A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU25752/95A AU2575295A (en) 1994-06-02 1995-05-31 Process for producing optically active propargyl alcohol compound

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP12145994 1994-06-02
JP6/121459 1994-06-02

Publications (1)

Publication Number Publication Date
WO1995033845A1 true WO1995033845A1 (fr) 1995-12-14

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Application Number Title Priority Date Filing Date
PCT/JP1995/001064 WO1995033845A1 (fr) 1994-06-02 1995-05-31 Procede de production d'un compose d'alcool propargylique optiquement actif

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AU (1) AU2575295A (fr)
WO (1) WO1995033845A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000061777A1 (fr) * 1999-04-12 2000-10-19 Chirotech Technology Limited Procede de preparation de precurseurs de la prostaglandine
US6214611B1 (en) 1999-04-12 2001-04-10 Chirotech Technology Limited Process for the preparation of prostaglandin precursors
WO2006076565A3 (fr) * 2005-01-14 2006-12-07 Schering Corp Preparation d'alcool propargylique chiral et d'intermediaires d'ester d'analogues d'himbacine
US7897795B2 (en) 2008-04-09 2011-03-01 Scinopharm Taiwan Ltd. Process for the preparation of prostaglandin analogues and intermediates thereof
CN103917665A (zh) * 2011-11-09 2014-07-09 纳幕尔杜邦公司 用于沙门氏菌检测的序列和它们的用法
WO2020255164A1 (fr) * 2019-06-21 2020-12-24 Council Of Scientific And Industrial Research Procédé chimio-enzymatique pour la préparation d'alcool homopropargylique

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH01171497A (ja) * 1987-12-26 1989-07-06 Lion Corp ラセミアルコールの光学分割法
JPH02262536A (ja) * 1989-04-01 1990-10-25 Arakawa Chem Ind Co Ltd 光学活性化合物およびその製法
JPH03210194A (ja) * 1990-01-11 1991-09-13 Konica Corp 多層分析素子

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH01171497A (ja) * 1987-12-26 1989-07-06 Lion Corp ラセミアルコールの光学分割法
JPH02262536A (ja) * 1989-04-01 1990-10-25 Arakawa Chem Ind Co Ltd 光学活性化合物およびその製法
JPH03210194A (ja) * 1990-01-11 1991-09-13 Konica Corp 多層分析素子

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000061777A1 (fr) * 1999-04-12 2000-10-19 Chirotech Technology Limited Procede de preparation de precurseurs de la prostaglandine
US6214611B1 (en) 1999-04-12 2001-04-10 Chirotech Technology Limited Process for the preparation of prostaglandin precursors
JP2002541816A (ja) * 1999-04-12 2002-12-10 カイロテック・テクノロジー・リミテッド プロスタグランジンプレカーサーの調製のための方法
WO2006076565A3 (fr) * 2005-01-14 2006-12-07 Schering Corp Preparation d'alcool propargylique chiral et d'intermediaires d'ester d'analogues d'himbacine
US7897795B2 (en) 2008-04-09 2011-03-01 Scinopharm Taiwan Ltd. Process for the preparation of prostaglandin analogues and intermediates thereof
US8436194B2 (en) 2008-04-09 2013-05-07 Scinopharm Taiwan, Ltd. Process for the preparation of prostaglandin analogues and intermediates thereof
US8742143B2 (en) 2008-04-09 2014-06-03 Scinopharm Taiwan, Ltd. Process for the preparation of prostaglandin analogues
CN103917665A (zh) * 2011-11-09 2014-07-09 纳幕尔杜邦公司 用于沙门氏菌检测的序列和它们的用法
CN103917665B (zh) * 2011-11-09 2016-11-16 纳幕尔杜邦公司 用于沙门氏菌检测的序列和它们的用法
WO2020255164A1 (fr) * 2019-06-21 2020-12-24 Council Of Scientific And Industrial Research Procédé chimio-enzymatique pour la préparation d'alcool homopropargylique
US12247239B2 (en) 2019-06-21 2025-03-11 Council Of Scientific & Industrial Research Chemo-enzymatic process for the preparation of homopropargylic alcohol

Also Published As

Publication number Publication date
AU2575295A (en) 1996-01-04

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