Stereoinversion of R‐Configured Secondary Alcohols Using a Single Enzymatic Approach

Abstract

AbstractHere, we achieved a single‐enzymatic stereoinversion of R‐configured alcohols to their corresponding S enantiomers in high percent conversion and high enantioselectivity. A single mutant of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH) oxidized R alcohols to their corresponding ketones under conditions that allow selectivity mistakes and then reduced them under stereoselective conditions to generate the corresponding S‐configured alcohols. The success of this stereoinversion relies on controlling the stereoselectivity of the oxidation and the reduction reactions by varying the amounts of acetone and 2‐propanol, respectively. Furthermore, the deployment of the TeSADH mutants W110A and W110G led to stereoinversion of enantiopure R alcohols to their S enantiomers in medium to high enantiomeric excess (up to >99% ee). The disclosed approach of single enzymatic stereoinversion presents a biocatalytic alternative to Mitsunobu inversion reaction.