Regio- and Enantioselective Construction of Tetrazole Hemiaminal Esters and Related Prodrugs via Biocatalytic Dynamic Kinetic Resolution

Abstract

Enzyme-catalyzed dynamic kinetic resolution was applied to the one-pot regio-and enantioselective synthesis of 2,5disubstituted tetrazole hemiaminal esters, among which 72% of the products were obtained in excellent enantiopurities (99% ees). Tunable stereoselectivity was achieved by using different types of enzymes during the synthesis of a key intermediate for a clinic drug candidate. Successful preparation of tetrazole ester prodrugs and high catalyst recyclability further demonstrated the potential practical application of this protocol.