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

Enzyme-catalyzed dynamic kinetic resolution was applied to the one-pot regio- and enantioselective synthesis of 2,5-disubstituted 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.

Enzyme-Catalyzed Dynamic Kinetic Resolution of 2-Formylbenzoic Acids for the Asymmetric Synthesis of Phthalidyl Esters and Related Prodrugs.

An enzyme-catalyzed dynamic kinetic resolution strategy was applied for the asymmetric synthesis of phthalidyl esters in high yields (up to 95%) and enantiomeric purities (up to 99% ee) through a direct one-pot procedure. Preparation of phthalidyl ester prodrugs and a scale-up reaction demonstrated the potential of this method for practical applications.

Multivalent butyrylcholinesterase inhibitor discovered by exploiting dynamic combinatorial chemistry.

In this study, we report the generation of a polymer-based dynamic combinatorial library (DCL) incorporating exchangeable side chains using acylhydrazone formation reaction. In combination with tetrameric butyrylcholinesterase (BChE), the most potent binding side chain was identified, and the information obtained was further used for the synthesis of a multivalent BChE inhibitor. In the in vitro biological evaluation, this multivalent inhibitor exhibited not only better inhibitory effect than the commercial reference but also high selectivity on BChE over acetylcholinesterase (AChE).