Our group has developed a new method for peptide synthesis through the Ag(I)-promoted reaction of thioamides with peptide C-terminal carboxylic acids, which has been exploited in the epimerisation-free synthesis of peptide in the N→C direction.1 More recently, we described a facile peptide macrocyclisation method that exploits the selective reactivity of peptide thioamides to generate isoimide intermediates, which undergo spontaneous intramolecular acyl transfer to furnish native cyclic peptides.2
Herein, we describe the elaboration of our Ag(I)-promoted transformation of peptide thioamides to the macrolactonisation of peptides. This new method enables the preparation of depsipeptides and overcomes the common drawbacks of standard macrolactonisation methods such as cyclisation yields and limited reactivity of the Thr/Ser hydroxyl group.