Efficient Method for Cyclic Peptide Synthesis Mediated by Acylammonium Species

Key words

cyclization - specialty peptides - natural products - continuous flow - acylammonium

Significance

Cyclic peptides are one of the most useful compounds as drugs. Although these compounds are generally synthesized by head-to-tail cyclization, the use of an excess amount of expensive coupling reagents and long reaction times are problematic. The authors have revealed that the acyl­ammonium species generated from inexpensive tertiary amine and alkylchloroformate is an efficient coupling reagent for this approach.

Comment

Acylammonium species selectively ­react with C-terminal carboxylate by ionic interaction to give the active anhydride. Subsequently, head-to-tail cyclization occurs smoothly at the C-terminal anhydride with N-terminal amine. This method dramatically improved the efficiency of reactivity compared with traditional pathways to synthesize penta- and tetra-peptides.

Publikationsverlauf

Artikel online veröffentlicht:
14. Juli 2023