Rapid, Traceless, AgI‐Promoted Macrocyclization of Peptides Possessing an N‐Terminal Thioamide. Issue 15 (8th March 2019)

• Record Type: Journal Article
• Authors: Thombare, Varsha J.; Hutton, Craig A.
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 15(2019)
• Page Start: 4998
• Page End: 5002
• Publication Date: 2019-03-08
• Subjects: cyclic peptide -- macrocyclization -- thioamide; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201900243
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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: chemoselectively activating the thioamide and tethering the N‐terminal thioamide to the C‐terminal carboxylate. Extrusion of Ag2 S 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. Abstract : Silver lining : A new method for peptide macrocyclization is described, which employs the Ag I ‐promoted transformation of peptide thioamides. The Ag I chemoselectively activates the thioamide and tethers the N‐terminal thioamide to the C‐terminal carboxylate. Using this method, cyclic peptides are produced in high yields within 1 hour, free of epimerization and cyclodimerization.