Method for preparing (S)-(4-chlorphenyl)-(pyridine-2-yl)-methanol by utilizing microbial catalysis

Abstract

The invention relates to a method for preparing (S)-(4-chlorphenyl)-(pyridine-2-yl)-methanol by utilizing microbial catalysis, and belongs to the technical field of biological catalysis. According to the method, 4-chlorphenyl-(pyridine-2-yl)-ketone is subjected to asymmetrical reduction by utilizing kluyveromycessp (CCTCCM 2011385) whole cells to synthesize the (S)-(4-chlorphenyl)-(pyridine-2-yl)-methanol. The method comprises the following steps of: sieving a microbe which has high-stereoselectivity carbonyl reductase activity on a prochiral ketone substrate, determining a series of conditions of asymmetrical reduction reaction, such as reaction temperature, pH, the concentration of cells, the concentration of the substrate and reaction time and additives (including various secondary solvents, polyethyleneglycol (PEG), phosphates and the like), wherein the enantiomer excess value and yield of the (S)-(4-chlorphenyl)-(pyridine-2-yl)-methanol serving as a product can reach 86.7 percent e.e and 92.1. The product is separated and extracted initially by silicagel column chromatography, so that the purity of the separated product is 99.2 percent, and the extraction yield is 56.7 percent.

Description

technical field

[0001] A method for preparing (S)-(4-chlorophenyl)-(pyridin-2-yl)-methanol by catalytic asymmetric reduction of whole cells of microorganisms, that is, using whole cells of microorganisms to asymmetrically reduce 4-chlorophenyl-( Pyridin-2-yl)-methanone is an important chiral intermediate for the synthesis of betahistines ( S )-(4-chlorophenyl)-(pyridin-2-yl)-methanol belongs to the technical field of biocatalysis. Background technique

[0002] Betahistine drugs are a class of second-generation antihistamine drugs with high efficiency and low toxicity and side effects. They can be used to treat allergic rhinitis and other allergic diseases. They have the advantages of rapid action, high selectivity, low side effects, and significant curative effect. . Due to the rapid increase in the incidence of allergic diseases in recent decades, the demand for betahistines, which play an important role in the treatment of allergic diseases, is increasing. The same seco...

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