Tengyun Wei, Jiawei Tang, Guowei Ni
Aug 30, 2019
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Influential Citations
13
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Journal
Organic Process Research & Development
Abstract
(S)-2-Chloro-1-(2,4-dichlorophenyl) ethanol (3) is a chiral intermediate in the synthesis of luliconazole ((R)-E-1). Here, we report a novel biopreparation of 3 by bioreduction of 2-chloro-1-(2,4-dichlorophenyl) ethanone (2) using recombinant Escherichia coli expressing LK08, a ketoreductase mutant from Lactobacillus kefiri, as a biocatalyst. The reaction conditions for the biotransformation including pH, temperature, and concentration of isopropanol and NADP+, as well as the amount of recombinant E. coli cells, were optimized to improve the process productivity. When the enzymatic process was carried out on a 300 g scale under the optimized conditions, the ketone 2 was fully converted to chiral alcohol 3 with a product ee value of >99%. Furthermore, 3 was isolated and used to chemically synthesize luliconazole with 38% yield and 99% ee. This study presents an efficient and cost-effective chemoenzymatic process for the production of (R)-E-1.