N‐Formylation of Amino Acid Esters and Peptides via Peroxide–Mediated Decarboxylative Coupling with α‐Keto Acids

An environmentally benign approach for the synthesis of N-formyl amino acid derivatives and peptides via decarboxylative C─N coupling of alpha ketoacids, where carbon dioxide and water/tertiary butanol were formed as by-product. Here, f-Met, a peptide biosynthesis initiator, and f-MLP, an antibacterial tripeptide, and several ferrocenyl amino acid bioconjugates were synthesized.

Abstract

N-formyl amino acids and peptides play a crucial role in protein biosynthesis and in the design and development of antimicrobial peptides. In this study, we report an efficient N-formylation of amino acid esters and peptides with α-keto acids via peroxide-mediated decarboxylative coupling, where only water/tertiary butanol and carbon dioxide were formed as by-products. H₂O₂ was found to be ideal for the N-formylation of substituted amino acids, while TBHP was successful for unprotected amino acid esters and oligopeptides. The methodology was extended for the synthesis of bioactive N-formyl methionine and f-MLP. The synthesized library includes N-ferrocenyl-N-formyl amino acid and peptide derivatives, which might serve as a hybrid material for medicinal and electrochemical applications.

Zum Volltext