Stereoselective diversification of α-amino acids enabled by N-heterocyclic carbene catalysis.

ABSTRACT: Chiral α-amino acids (AAs), essential to biological systems and drug design, drive demand for precise synthetic methods to access unnatural variants (UAAs) and stereochemically defined peptides. We report an N-heterocyclic carbene (NHC)-catalyzed strategy enabling enantioselective synthesis of α-(U)AA esters and peptides. Leveraging NHC-generated acyl azolium intermediates, this approach achieves dynamic kinetic resolution of racemic or chiral α-(U)AAs with broad substrate scope, including sterically hindered and unsaturated derivatives. Stereodivergent synthesis is accomplished via NHC-mediated proton shuttling, which usually furnishes enantio-complementary α-(U)AAs and peptides with >90% ee (de). Mechanistic studies establish that N,N'-diisopropylcarbodiimide activates α-(U)AAs to form o

SUBMITTER: Zhang H 

PROVIDER: S-EPMC12511568 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature