Practical Two‐Step Synthesis of an Enantiopure Aliphatic Terminal (S)‐Epoxide Based on Reduction of Haloalkanones with “Designer Cells”

A practical biocatalytic method for the synthesis of aliphatic β‐halogenated (S)‐alcohols as epoxide precursors by means of an enantioselective reduction of the corresponding ketones with recombinant whole cells, bearing an alcohol dehydrogenase and a glucose dehydrogenase, was developed. The biotransformations operate at high substrate concentrations of up to 208 g/L, and afford the (S)‐β‐halohydrins with both high conversions of >95 % and enantioselectivities of >99 % ee. Base‐induced cyclization of the β‐halohydrin intermediates gave the desired (S)‐epoxides in high yield and enantiomeric purity (>99 % ee).