School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria, 3010, Australia.
Angew Chem Int Ed Engl. 2019 Apr 1;58(15):4998-5002. doi: 10.1002/anie.201900243. Epub 2019 Mar 8.
Peptide macrocyclization is often a slow process, plagued by epimerization and cyclodimerization. Herein, we describe a new method for peptide macrocyclization employing the Ag -promoted transformation of peptide thioamides. The Ag has a dual function: chemoselectively activating the thioamide and tethering the N-terminal thioamide to the C-terminal carboxylate. Extrusion of Ag 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.
肽大环化通常是一个缓慢的过程，受到外消旋化和环二聚化的困扰。在此，我们描述了一种利用 Ag 促进肽硫酰胺转化的新的肽大环化方法。Ag 具有双重功能：选择性地激活硫酰胺并将 N 端硫酰胺键接到 C 端羧酸盐上。AgS 的挤出生成异亚胺中间体，该中间体发生酰基转移以生成天然环状肽，从而实现快速、无痕的大环化过程。在 1 小时内以高产率提供环状肽，无外消旋化和环二聚化。
