Chemoenzymatic Synthesis of Optically Pure <scp>l</scp>- and <scp>d</scp>-Biarylalanines through Biocatalytic Asymmetric Amination and Palladium-Catalyzed Arylation

Abstract

A chemoenzymatic approach was developed and optimized for the synthesis of a range of N-protected nonnatural l- and d-biarylalanine derivatives. Starting from 4-bromocinnamic acid and 4-bromophenylpyruvic acid using a phenylalanine ammonia lyase (PAL) and an evolved d-amino acid dehydrogenase (DAADH), respectively, both enantiomers of 4-bromophenylalanine were obtained and subsequently coupled with a panel of arylboronic acids to give the target compounds in high yield and optical purity under mild aqueous conditions.