Stereoselective Synthesis of β-Branched Aromatic α-Amino Acids by Biocatalytic Dynamic Kinetic Resolution**

beta-Branched noncanonical amino acids are valuable molecules in modern drug development efforts. However, they are still challenging to prepare due to the need to set multiple stereocenters in a stereoselective fashion, and contemporary methods for the synthesis of such compounds often rely on the use of rare-transition-metal catalysts with designer ligands. Herein, we report a highly diastereo- and enantioselective biocatalytic transamination method to prepare a broad range of aromatic beta-branched alpha-amino acids. Mechanistic studies show that the transformation proceeds through dynamic kinetic resolution that is unique to the optimal enzyme. To highlight its utility and practicality, the biocatalytic reaction was applied to the synthesis of several sp(3)-rich cyclic fragments and the first total synthesis of jomthonic acid A.

Automated summary

A highly diastereo- and enantioselective biocatalytic transamination method was developed for the preparation of a broad range of aromatic beta-branched alpha-amino acids. The transformation proceeds through dynamic kinetic resolution unique to the optimal enzyme, showcasing its utility for the synthesis of sp(3)-rich cyclic fragments and total synthesis of jomthonic acid A.