Efficient Biocatalytic Synthesis of Chiral Intermediate of Pregabalin Using Immobilized Lipase.

Biomed Res Int

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.

Published: March 2019


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Article Abstract

A mutant L206F/P207F/L259F of lipase (TTL) exhibited high hydrolytic activity towards 2-carboxyethyl-3-cyano-5-methylhexanoic acid ethyl ester (CNDE) for synthesis of ()-2-carboxyethyl-3-cyano-5-methylhexanoic acid (-CCMA), a key chiral intermediate of pregabalin. However, low conversion at high CNDE concentration and unreusability of the free TTL mutant restricted its industrial applications. In this study, the TTL mutant was immobilized onto epoxy resin and its catalytic properties for kinetic resolution of CNDE were investigated. Under the optimized conditions, the immobilized lipase exhibited an increased catalytic efficiency even at a CNDE concentration of 3 M with 49.7% conversion and 95% . The conversion retained higher than 46.3% even after 10 times repeated use of the immobilized lipase in -heptane-water biphasic system. These results demonstrated great potential of the immobilized TTL mutant for industrial production of the chiral intermediate of pregabalin.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236560PMC
http://dx.doi.org/10.1155/2018/6192059DOI Listing

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