Electro-enzymatic Cascade Stereodivergent Synthesis of β-Hydroxy Selenides via Engineered Ketoreductases.

Abstract

Chiral selenium-containing molecules have found extensive applications in organic synthesis and drug discovery. In this study, we developed a method for the stereodivergent synthesis of chiral β-hydroxy selenides in high yields and remarkable stereoselectivity through electro-enzyme cascade catalysis. Furthermore, the synthesis of two chiral configurations can be regulated by modifying keto reductases. Notable advantages of this protocol over previous methods include the use of green solvents, one-pot, and atom-economical processes under mild reaction conditions. Control experiments and molecular docking technique were employed to investigate the reaction, highlighting the significant impact of the mutation site on the catalytic stereoselectivity of KRED.