A practical Piv2O-mediated method for N-methylated peptide synthesis via in situ generation of pivaloyl mixed anhydrides is developed under mild, base-free conditions. It features high yields, good substrate compatibility, and excellent racemization suppression, outperforming conventional coupling reagents. The method is successfully applied to synthesize cyclosporin A fragments and ciliatamide B.
Liu et al. (Wed,) studied this question.