Biosynthesis preparation method of (R)-3-hydroxyalkanoate

A hydroxyalkanoate and biosynthesis technology, applied in fermentation and other directions, can solve problems such as poor stability, affecting the yield and purity of chiral alcohol, and the existence of monomer forms, so as to reduce dosage, reduce metabolic burden, and increase curative effect Effect

Inactive Publication Date: 2013-06-12
曾方 +2
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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

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  • Biosynthesis preparation method of (R)-3-hydroxyalkanoate

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Embodiment Construction

[0018] The present invention is further described below in conjunction with specific embodiment, but protection scope of the present invention is not limited thereto:

[0019] Enzyme extraction method was used to obtain β-ketothiolase (phbA), acetoacetyl-CoA reductase (phbB) and PHA synthase (phbC) necessary for the biosynthesis of poly(R)-3-hydroxyalkanoic acid; Technology Construct the above enzymes into the E. Coli gene to obtain a stable strain suitable for industrial production;

[0020] Bacterial growth medium: yeast powder 3g / L, peptone 8g / L, sodium chloride 10g / L, PH7.0

[0021] The obtained gene recombinant bacteria are fermented and cultured for 72 hours, centrifuged for solid-liquid separation, the organic phase is extracted from the solid phase, concentrated, and dried to obtain poly(R)-3-hydroxybutyric acid.

[0022] Fermentation medium: Na 2 HPO 4 .12H 2 O 3g / L, KH 2 PO 4 0.5g / L, (NH 4 ) 2 SO 4 1.0g / L, MgSO 4 0.5g / L NaCl 0.5g, glucose 60g / L;

[0023...

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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...

Claims

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Application Information

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IPC IPC(8): C12P7/62
Inventor 曾方黄璐曾媛
Owner 曾方
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