Rapid, traceless, Ag(I)‐promoted macrocyclization of peptides possessing an N‐terminal thioamide

Peptide macrocyclization is often a slow process, plagued by epimerization and cyclodimerization. Herein we describe a new method for peptide macrocyclization employing the Ag(I)‐promoted transformation of peptide thioamides. The Ag(I) has a dual function: chemselectively activating the thioamide and tethering the N‐terminal thioamide to the C‐terminal carboxylate. Extrusion of Ag2S generates an isoimide intermediate, which undergoes acyl transfer to generate the native cyclic peptide, resulting in a rapid, traceless macrocylization process. Cyclic peptides are furnished in high yields within 1 hour, free of epimerization and cyclodimerization.

from A via a.sfakia on Inoreader http://bit.ly/2GQW4yP