Chemistry: molecular biology and microbiology – Process of utilizing an enzyme or micro-organism to destroy... – Resolution of optical isomers or purification of organic...
Patent
1991-02-07
1993-08-03
Robinson, Douglas W.
Chemistry: molecular biology and microbiology
Process of utilizing an enzyme or micro-organism to destroy...
Resolution of optical isomers or purification of organic...
435146, C12P 742
Patent
active
052328538
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a process for producing optically active 3-hydroxy-2-methylbutyrates which are useful starting materials for synthesis of good ferroelectric liquid crystal compounds and the like.
Namely, when 2-methyl-3-oxobutyrates of the formula: ##STR1## wherein R is an ester forming group, is reduced according to an ordinary chemical method, for example, by using NaHB.sub.4, the following four stereomers are formed due to asymmetric carbon atoms at 2- and 3-positions. ##STR2## wherein, R is as defined above and the symbol in the parentheses represents the absolute configuration of the asymmetric carbon atoms at 2- and 3-positions. Among these four stereomers, the present invention relates to a process for the selective production of the (2R, 3S)syn 2 isomers of the formula (2) by microbial asymmetric reduction. The isomer of the formula (2) are highly applicable to synthesis of good ferroelectric liquid crystal compounds as starting materials.
BACKGROUND ART
Known processes for producing optically active 3-hydroxy-2-methylbutyrates from 2-methyl-3-oxobutyrates of the formula (1) by microbial asymmetric reduction include the processes using baker's yeast [A. Furuichi et al., Agric. Biol. Chem., 49, 9, 2563-2570 (1985); K. Nakamura et al., Tetrahedron Letters, 27, 3155 (1986); and K. Nakamura et al., Bull. Chem. Soc. Jpn., 62, 1179 (1989)] and the process using other yeast such as Candida albicans [H. Akita et al., Chem. Pharm. Bull., 31, 4376 (1983)]. However, these processes are not industrially advantageous processes in view of their low diastereomer selectivity and/or enantiomer selectivity. Further, microbial asymmetric reduction of 2-methyl-3-oxobutyrates with bacteria has not been known heretofore in the prior art.
OBJECTS OF THE INVENTION
The main object of the present invention is to provide a process for selectively and efficiently producing optically active 3-hydroxy-2-methylbutyrates of the formula (2), which are useful starting materials for synthesis of good ferroelectric liquid crystal compounds, polyoxoantibiotics, various naturally occurring physiologically active substances and the like, from the corresponding 3-oxo esters of the formula (1) by using microorganisms, particularly, bacteria.
This object as well as other objects and advantages of the present invention will become apparent to those skilled in the art from the following description.
SUMMARY OF THE INVENTION
The present inventors have found that microbial asymmetric reduction of 2-methyl-3-oxobutyrates of the formula (1) can be efficiently conducted by using bacteria to form the desired optically active 3-hydroxy isomers.
Namely, according to the present invention, there is provided a process for producing a (2R,3S)-3-hydroxy-2-methylbutyrate of the formula (2) which comprises subjecting a 2-methyl-3-oxobutyrate of the formula (1) to asymmetric reduction with a bacterial strain or its processed material.
DISCLOSURE OF THE INVENTION
In the process of the present invention, the ester forming group represented by R in the 2-methyl-3-oxobutyrate of the formula (1) used as the starting material is not specifically limited. For example, R may be lower alkyl, alkoxyalkyl or aralkyl. Examples of lower alkyl include alkyl having 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, neopentyl, hexyl and the like. Examples of alkoxyalkyl include alkoxyalkyl having 3 to 6 carbon atoms such as methoxyethyl, ethoxyethyl, butoxyethyl and the like. Examples of aralkyl include phenyl(lower)alkyl such as benzyl, phenethyl, 1-methylbenzyl, 1-ethylbenzyl, 1-methylphenethyl, 2-methylphenethyl, 2-ethylphenethyl and the like. Among them, ethyl 2-methyl-3-oxobutyrate, isobutyl 2-methyl-3-oxobutyrate, butoxyethyl 2-methyl-3-oxobutyrate and benzyl 2-methyl-3-oxobutyrate are preferred. Particularly, ethyl 2-methyl-3-oxobutyrate is preferred from a practical point of view.
Although the formula (1) represents the keto tautomer, the compounds of the formu
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Chemical Abstracts, vol. 108, No. 9, Feb. 29, 1988, (Columbus, Ohio, US), Buisson, Didier et al.: "New chiral building blocks by microbial asymmetricreduction: a direct access to functionalized 2R,3R- and 2S,3R-2-methyl-3-hydroxy butyrate synthons", see p. 341, abstract 71630q, & Tetrahedron Lett. 1987, 28(42), 5033-5036.
Chemical Abstracts, vol. 100, No. 17, Apr. 23, 1984, (Columbus, Ohio, US), Akita, Hiroyuki et al.: "The use of microorganisms in organic synthesis. I. Microbiological asymmetric reduction of 2-methyl-3-oxo.dbd.butyrates", see p. 504, abstract 137316k, & Chem.Pharm.Bull. 1983, 31(12), 4376-4383.
Chemical Abstracts, vol. 103, No. 25, Dec. 23, 1985, (Columbus, Ohio, US), Furuichi, Akiya et al.: "Enzymes producing two chiral centers. Part I. Purification and properties of an asymmetric reduction enzyme of 2-methyl-3-oxobutyrate in bakers' yeast.", see p. 401, abstract 209519r, & Agric.Biol.Chem. 1985, 49(9), 2563-2570.
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Kawada Mitsuru
Miya Hiroyuki
Sugiyama Yoshio
Robinson Douglas W.
Saucier S.
Takeda Chemical Industries Ltd.
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