Synthesis of α-Alkyl-β-Hydroxy Amides through Biocatalytic Dynamic Kinetic Resolution Employing Alcohol Dehydrogenases

Abstract

Chiral (α-substituted) β-hydroxy amides are interesting derivatives as they are useful building blocks of many biologically active compounds. Herein, the biocatalytic stereocontrolled synthesis of various acyclic syn-α-alkyl-β-hydroxy amides through a dynamic kinetic resolution is shown. Hence, a series of overexpressed alcohol dehydrogenases (ADHs) in Escherichia coli was used to reduce the corresponding racemic β-keto amides. Among them, ADH-A from Rhodococcus ruber and commercial evo-1.1.200 afforded the best activities and selectivities, giving access to the opposite enantiomers with high diastereomeric excess and excellent enantiomeric excess. Some of these compounds were obtained at semipreparative scale. (Figure presented.).