Method for preparing (S)-6-hydroxy-8-chlorine ethyl caprylate through reductase

Abstract

The invention discloses a method for preparing (S)-6-hydroxy-8-chlorine ethyl caprylate through reductase and belongs to the technical field of biological catalysis. The method comprises the steps that mixed spinning 6-carbonyl-8-chlorine ethyl caprylate, ethanol, a buffer agent and glucose are sequentially added into a reaction container provided with a stirring device, the stirring device is turned on to conduct stirring until the glucose is dissolved fully, lactic dehydrogenase and coenzyme are added into the reaction container to conduct a reaction, the reaction temperature, the reaction time and the pH value of the buffer agent of a reaction system in the reaction process are controlled, extraction is conducted after the reaction is finished, vacuum concentration is conducted, and then the (S)-6-hydroxy-8-chlorine ethyl caprylate is obtained. The conversion rate of the target product of the (S)-6-hydroxy-8-chlorine ethyl caprylate obtained through reduction reaches 100 percent, the yield is 94 percent or more, the ee value is 99 percent or more, the value of industrially amplifying production is achieved, and an economical basis capable of meeting the requirement for environment protection is laid for preparation of (R)-lipoic acid.

Description

technical field [0001] The invention belongs to the technical field of biological catalysis, and in particular relates to a method for preparing (S)-6-hydroxy-8-chlorooctanoic acid ethyl ester by a reductase, and a carbonyl reductase asymmetric reduction gyration 6-carbonyl-8-chlorooctanoic acid ethyl ester A method for the preparation of (R)-lipoic acid chiral intermediate (S)-6-hydroxy-8-chlorooctanoic acid ethyl ester. Background technique [0002] The English name of 6-hydroxy-8-chlorooctylic acid ethyl ester is: 6-hydroxy-8-chlorine octylic acid ethyl ester, the molecular formula is: C 10 H 19 O 3 Cl; molecular weight: 222.71, its structure is shown in the following formula, it is a chemical reaction intermediate, used for the synthesis of 6,8-dichlorooctanoic acid ethyl ester, and 6,8-dichlorooctanoic acid ethyl ester is the synthesis of lipoic acid important intermediate. [0003] [0004] R-lipoic acid (Lipoic acid) is a vitamin B compound and is a coenzyme th...

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Problems solved by technology

Due to the complex process of this method, multiple crystallizations are required, the yield is low, the cost is high, and the resolution yield is not more than 50%. At the same time, (S)-lipoic acid cannot be effectively utilized, resulting in waste of resources and environmental pollution.

[0007] Chinese Patent Authorization Announcement No. CN100558905C and papers published by Yang Qian (bioprocessing, 6 (4), 13-18; 2008) are all in the research of enzymatic resolution and preparation of (R)-6-hydroxyl-8-chlorooctanoic acid ethyl ester method, its total yield is at 46.7%, ee value is 93.8%, all are not very ideal, can not improve yield, simultaneously (S)-6-hydroxyl-8-chlorooctanoic acid ethyl ester fails to utilize effectively

[0009] Invention Patent Publication No. CN103451124.A recommends "a strain of Rhodococcus and its use for preparing optically pure (R)-6-hydroxy-8-chlorooctanoate and other optically active chiral alcohols", just as the aforementioned CN100558905C only studies The preparation of R-6-hydroxyl-8-chlorooctanoic acid ethyl ester, because R-6-hydroxyl-8-chlorooctanoic acid ethyl ester is difficult to obtain high-purity R-lipoic acid, it is easier to obtain S-lipoic acid, so it does not have The basis of industrialized mass production

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