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

Abstract

Here, 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.