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Stereoselective Synthesis of β‐Branched Aromatic α‐Amino Acids by Biocatalytic Dynamic Kinetic Resolution **
Author(s) -
Li Fuzhuo,
Yang LiCheng,
Zhang Jingyang,
Chen Jason S.,
Renata Hans
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202105656
Subject(s) - kinetic resolution , transamination , stereocenter , enantioselective synthesis , stereoselectivity , chemistry , amino acid , combinatorial chemistry , biocatalysis , catalysis , stereochemistry , organic chemistry , enzyme , reaction mechanism , biochemistry
Abstract β‐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 β‐branched α‐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.