Biosynthesis preparation method of (R)-3-hydroxyalkanoate

Abstract

The invention discloses a biosynthesis preparation method of (R)-3-hydroxyalkanoate as a chiral pharmaceutical intermediate. The (R)-3-hydroxyalkanoate has a general formula shown in the patent specification. The biosynthesis preparation method comprises preparing poly(R)-3-hydroxyalkanoate by a microbial fermentation method, synthesizing a homopolymer or a co-polymer of the poly(R)-3-hydroxyalkanoate from different matrixes by a change of a carbon source, and directly preparing the (R)-3-hydroxyalkanoate from the poly(R)-3-hydroxyalkanoate by an alcoholysis-esterification method. The biosynthesis preparation method solves the problem that the traditional chemical method and the chiral separation method for producing the (R)-3-hydroxyalkanoate have defects of high costs, low purity and low chirality and cannot be industrialized, and provides a high-efficiency and low-cost production approach.

Description

technical field [0001] The invention relates to a chiral pharmaceutical intermediate, in particular to a biosynthetic preparation method of the chiral pharmaceutical intermediate (R)-3-hydroxyalkanoate. Background technique [0002] The general formula of (R)-3-hydroxyalkanoate involved in the present invention is: where R 1 It is a saturated or unsaturated, straight chain or alkyl group containing side chains and substituents (such as methyl, ethyl, propyl, butyl, etc.), R 2 is alkyl, cycloalkyl, aryl or aralkyl (such as propyl, tert-butyl, phenyl, benzyl, etc.). There are functional groups of hydroxyl and carboxyl in the 3-hydroxyalkanoate molecule, and the hydroxyl and carbonyl are active groups, which can be used as important intermediates in organic synthesis and have a wide range of uses, especially the monochiral isomer (R)- 3-hydroxyalkanoate and (S)-3-hydroxyalkanoate can be used as pharmaceutical intermediates and have broad prospects in the synthesis of chiral...

AI Technical Summary

Problems solved by technology

[0008] Chinese patents CN101864457A and CN101864458A use recombinant strains for fermentation to obtain (R)-3-hydroxybutyric acid, and then use methanol or ethanol as a substrate to obtain (R)-3-hydroxybutyrate methyl or ethyl Ester, since (R)-3-hydroxybutyric acid molecule has carboxyl and hydroxyl groups at the same time, it is easy to undergo self-polymerization or decompose into crotonic acid and water, which has poor stability and is difficult to exist in the form of monomers, which affects the next step of esterification Yield and Purity of Produced Chiral Alcohols

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