Chemistry: molecular biology and microbiology – Process of utilizing an enzyme or micro-organism to destroy... – Resolution of optical isomers or purification of organic...
Reexamination Certificate
2000-10-26
2002-06-18
Saucier, Sandra E. (Department: 1651)
Chemistry: molecular biology and microbiology
Process of utilizing an enzyme or micro-organism to destroy...
Resolution of optical isomers or purification of organic...
C435S158000, C435S126000
Reexamination Certificate
active
06406904
ABSTRACT:
TECHNICAL FIELD
The present invention relates to biochemically preparing methods of a C4 optically active compound, namely an optically active 4-halogeno-1,3-butanediol, and its derivatives, namely an optically active 1,2,4-butanetriol and an optically active 3-hydroxy-&ggr;-butyrolactone, which are very important as intermediates in making optically active compounds, such as pharmaceuticals, agrochemicals or physiologically active compounds.
PRIOR ART
1) As to a process for preparing an optically active 4-halogeno-1,3-butanediol, there is known a process for preparing it by reducing an optically active 4-halogeno-3-hydroxybutanoic acid ester with sodium boron hydrate or calcium boron hydrate (Japanese Patent Publication A 2-174733, Japanese Patent Publication A 9-77759 and Japanese Patent Publication B 7-76209).
2) As to a biochemically preparing method of an optically active 1,2,4-butanetriol, Nikaido et al. reported a process of it by reacting racemic 1,2,4-butanetriol with a microorganism belonging to the genus Pseudomonas to degrade (S)-1,2,4-butanetriol and by recovering (R)-1,2,4-butanetriol from the residual (Japanese Patent Publication A 6-209781). However, according to this method only (R)-1,2,4-butanetriol is obtainable, but (S)-1,2,4-butanetriol is not obtainable.
3) As to a biologically preparing method of an optically active 3-hydroxy-&ggr;-butyrolactone, there is a known process for preparing it by reacting resting cells of a microorganism with a racemic 4-chloro-3-hydroxybutanoic acid ester (Japanese Patent Publication A 9-47296, and Enzyme Microb. Technol., 24, 13-20(1999)).
4) A biochemical resolution of chlorohydrin and its derivatives was disclosed in Japanese Patent Publication A 9-47296, but there is no concrete description on the use of a 4-halogeno-1,3-butanediol as a substrate. Furthermore, there is neither description on the biochmical conversion from an optically active 4-halogeno-1,3-butanediol to an optically active 1,2,4-butanetriol or an optically active 3-hydroxy-&ggr;-butyrolactone.
5) There has been no report on the conversion into an optically active 1,2,4-butanetriol or an optically active 3-hydroxy-&ggr;-butyrolactone by using an optically active 4-chloro-1,3-butanediol as a substrate. As a matter of course, any example using biological catalyst such as a microorganism in that conversion has not been reported.
DETAILED DESCRIPTION OF THE INVENTION
An optically active 4-halogeno-1,3-butanediol, an optically active 1,2,4-butanetriol and an optically active 3-hydroxy-&ggr;-butyrolactone are very important as intermediates in making pharmaceuticals, agrochemicals or physiologically active compounds and therefore, more economical and more convenient processes for preparing them have been desired.
The present inventors extensively engaged in study for solving the above problems and completed the present invention.
The present invention relates to a process for preparing an optically active 4-halogeno-1,3-butanediol represented by the formula [1]
and (R)-1,2,4-butanetriol represented by the formula [2]
or (S)-3-hydroxy-&ggr;-butyrolactone represented by the formula [3]
which comprises reacting a racemic 4-halogeno-1,3-butanediol represented by the formula [1] with a microorganism, its culture broth or an enzyme(s) derived from said microorganism to prepare the optically active compound[1] and the compound[2] in (R)-form or the compound[3] in (S)-form.
That is, the method of the present invention comprises reacting a racemic 4-halogeno-1,3-butanediol[1] with a specific microorganism belonging to the genus Pseudomonas, its culture broth or an enzyme(s) derived from said microorganism to cause to stereoselective dehalogenation of a (R)-4-halogeno-1,3-butanediol[l], and by kinetic resolution obtaining a (S)-4-halogeno-1,3-butanediol[1] remained in the reaction solution and (R)-1,2,4-butanetriol[2] formed (abbreviated as (R)-form[2]), or reacting a racemic 4-halogeno-1,3-butanediol[1] (abbreviated as racemate[1]) with a specific microorganism belonging to the genus Pseudomonas, its culture broth or an enzyme(s) derived from said microorganism to cause to stereoselective dehalogenation of a (S)-4-halogeno-1,3-butanediol[1] (abbreviated as (S)-form[1]), and by kinetic resolution obtaining a (R)-4-halogeno-1,3-butanediol[1] (abbreviated as (R)-form[1]) remained in the reaction solution and (S)-3-hydroxy-&ggr;-butyrolactone[3] (abbreviated as (R)-form[3]) produced.
More in detail, the present invention relates to (i) a process for preparing (S)-form [1] and/or (R)-form [2] by reacting racemate [1] with Pseudomonas sp. DS-K-436-1, its culture broth or an enzyme(s) derived from said strain to prepare (S)-form [1] and (R)-form [2] and then isolating the resulting (S)-form [1] and/or (R)-form [2], and (ii) a process for preparing (R)-form [1] and/or (S)-form [3] by reacting racemate [1] with Pseudomonas sp. DS-SI-5, its culture broth or an enzyme(s) derived from said strain to prepare (R)-form [1] and (S)-form [3] and then isolating the resulting (R)-form [1] and/or (S)-form [3].
The present invention relates to, also a process for converting an optically active compound[1] into an optically active compound[2] or an optically active compound[3] with a microorganism belonging to the genus Pseudomonas or its culture broth or an enzyme(s) derived from said microorganism without any substantial racemization.
More in detail, the present invention relates to a process for an optically active compound[2] by reacting an optically active compound[1] with Psedomonas sp. DS-K-436-1, Psedomonas sp. OS-K-29, its culture broth, or an enzyme(s) derived from the strain,
and a process for preparing an optically active compound[3] by reacting an optically active [1] with Psedomonas sp. DS-SI-5, its culture broth, or an enzyme(s) derived from the strain.
As mentioned above, according to the present invention, there can be economically and conveniently obtainable a C4 optically active compound, that is an optically active 4-halogeno-1,3-butanediol [1], an optically active 1,2,4-butanetriol [2] and an optically active 3-hydroxy-&ggr;-butyrolactone [3] in highly optical purity, which are very important as intermediates in making pharmaceuticals, agrochemicals or physiologically active compounds.
Racemate[1] which is used as the starting material in the present invention, can be easily obtained by reducing a racemic 4-halogeno-3-hydroxybutanoic acid ester such as racemic 4-chloro-3-hydroxybutanoic acid methyl ester with sodium boron hydrate or lithium aluminum hydride etc. [Comprehensive Organic Transformation, pp. 548-552(1989). by Richard C. Larock, VCH Publishers, Inc.; J. Am. Chem. Soc., 158-163(1950); Tetrahedron Lett., 2709-2712 (1987); Tetrahedron Lett., 6069-6072 (1987).
The present invention is in detail explained below.
In order to obtain (S)-form[1] and (R)-form[2], or (R)-form[1] and (S)-form[3] from racemate[1] as a substrate, a microorganism belonging to the genus Pseudomonas having stereoselective dehalogenating activity, namely Psedomonas sp. DS-K-436-1, or Psedomonas sp. DS-SI-5 is cultivated and thereto a substrate, racemate[1] is added to react the microorganism.
The reaction is preferably carried out within optimum pH of the strain used herein and optimum temperature.
When pH gradually becomes lower by halogen ion released from the substrate[1] with progress of the reaction, it is necessary to adjust pH of the reaction solution to optimum pH by addition of an alkali. The solution is preferably controlled in the range of optimum pH by using an acid
Idogaki Hideaki
Kasai Naoya
Nakagawa Atsushi
Suzuki Toshio
Daiso Co. Ltd.
Saucier Sandra E.
Wenderoth , Lind & Ponack, L.L.P.
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