Rapid,Traceless, AgI‐Promoted Macrocyclization of Peptides Possessing an N‐Terminal Thioamide |
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Authors: | Varsha J. Thombare Craig A. Hutton |
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Abstract: | Peptide macrocyclization is often a slow process, plagued by epimerization and cyclodimerization. Herein, we describe a new method for peptide macrocyclization employing the AgI‐promoted transformation of peptide thioamides. The AgI has a dual function: chemoselectively 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. |
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Keywords: | cyclic peptide macrocyclization thioamide |
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