초록
<P>(<I>S</I>)-2-Chloro-1-(2,4-dichlorophenyl) ethanol (<B>3</B>) is a chiral intermediate in the synthesis of luliconazole (<B>(<I>R</I>)-<I>E</I>-1</B>). Here, we report a novel biopreparation of <B>3</B> by bioreduction of 2-chloro-1-(2,4-dichlorophenyl) ethanone (<B>2</B>) using recombinant <I>Escherichia coli</I> expressing LK08, a ketoreductase mutant from <I>Lactobacillus kefiri</I>, as a biocatalyst. The reaction conditions for the biotransformation including pH, temperature, and concentration of isopropanol and NADP<SUP>+</SUP>, as well as the amount of recombinant <I>E. coli</I> 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 <B>2</B> was fully converted to chiral alcohol <B>3</B> with a product ee value of >99%. Furthermore, <B>3</B> 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 <B>(<I>R</I>)-<I>E</I>-1</B>.</P><BR>[FIG OMISSION]</BR>