One-Pot Cyclization and Cleavage of Peptides with -Terminal Cysteine via the -Acyl Shift of the -2-[Thioethyl]glycine Residue.

We developed a one-pot method for peptide cleavage from a solid support the -acyl shift of -2-[thioethyl]glycine and transthioesterification using external thiols to produce cyclic peptides through native chemical self-ligation with the -terminal cysteine. The feasibility of this methodology is validated by the syntheses of model short peptides, including a tetrapeptide, the bicyclic sunflower trypsin inhibitor SFTI-1, and rhesus Θ-defensin RTD-1. Synthesis of the whole peptide precursor can be fully automated and proceeds without epimerization or dimerization.