Asymmetric Reduction of Aryl Ketones by Enzymatic Catalysis with Engineered Ketoreductases.

Chiral benzylic alcohols serve as key intermediates in the pharmaceutical industry. Through structure-guided semirational engineering, a mutant library of ketoreductase KR8 was developed that catalyzes the stereoselective reduction of aryl ketones to chiral benzylic alcohols with high enantioselectivity. In combination with KR14, these ketoreductases form a stereocomplementary biocatalytic tool box featuring a broad substrate scope. For 12 aryl ketone substrates, the corresponding enantiomers of benzylic alcohols were all obtained with high stereoselectivity and conversion efficiency. This work provides an efficient biocatalytic strategy for the synthesis of chiral pharmaceutical intermediates.