Asymmetric biomimetic transamination of α-keto amides to peptides

• Published in: Nature communications Vol. 12; no. 1; pp. 5174 - 9
• Main Authors: Cai, Weiqi, Qiao, Xuelong, Zhang, Hao, Li, Bo, Guo, Jianhua, Zhang, Liangliang, Chen, Wen-Wen, Zhao, Baoguo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.08.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/77/883; 639/638/77/889; Amides; Amino acids; Asymmetry; Biological activity; Biomimetic materials; Biomimetics; Catalysts; Enantiomers; Humanities and Social Sciences; multidisciplinary; Peptides; Science; Science (multidisciplinary); Transaminases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25449-y

Peptides are important compounds with broad applications in many areas. Asymmetric transamination of α-keto amides can provide an efficient strategy to synthesize peptides, however, the process has not been well developed yet and still remains a great challenge in both enzymatic and catalytic chemistry. For biological transamination, the high activity is attributed to manifold structural and electronic factors of transaminases. Based on the concept of multiple imitation of transaminases, here we report N-quaternized axially chiral pyridoxamines 1 for enantioselective transamination of α-keto amides, to produce various peptides in good yields with excellent enantio- and diastereoselectivities. The reaction is especially attractive for the synthesis of peptides made of unnatural amino acids since it doesn’t need great efforts to make chiral unnatural amino acids before amide bond formation. Asymmetric transamination of α-keto amides could provide an efficient strategy to synthesise peptides, but has not been well developed yet. Here, the authors design chiral pyridoxamine catalyst and realize the asymmetric biomimetic transamination of α-keto amides, providing access to various peptides with excellent enantiopurities.