Enzymatic Synthesis of Unprotected α,β-Diamino Acids via Direct Asymmetric Mannich Reactions.

ABSTRACT: α,β-Diamino acids are important structural motifs and building blocks for numerous bioactive natural products, peptidomimetics, and pharmaceuticals, yet efficient asymmetric synthesis to access these stereoarrays remains a challenge. Herein, we report the development of a pyridoxal 5'-phosphate (PLP)-dependent enzyme that is engineered to catalyze stereoselective Mannich-type reactions between free α-amino acids and enolizable cyclic imines. This biocatalyst enabled one-step asymmetric enzymatic synthesis of the unusual pyrrolidine-containing amino acid L-tambroline at gram-scale with high enantio- and diastereocontrol. Furthermore, this enzymatic platform is capable of utilizing a diverse range of α-amino acids as the Mannich donor and various cyclic imines as the acceptor. By coupling wi

SUBMITTER: Liu S 

PROVIDER: S-EPMC11369767 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature