Synthesis of cyclic peptides via O–N-acyl migration

We describe here a novel and convenient synthesis of head-to-tail cyclic peptide avoiding racemization. Linear depsipeptides including a serine residue as the key element for ester bond formation and acyl transfer were synthesized on 2-chlorotrityl chloride resin. After cleavage from the resin, intramolecular head-to-tail cyclization was performed in solution by C-terminal activation of urethane protected O-acyl serine residue. After removal of the Nα-serine protecting group, the final step consisted in O–N-acyl migration reaction on the ‘switch’ or ‘click’ element to restore native cyclic peptides.