Rapid and Green Anion-Assisted Mechanochemical Peptide Cyclization

A novel mechanochemical approach is described for chloride-templated head-to-tail macrocyclization of a pentapeptide and a hexapeptide. This straightforward method allows the solvent-free preparation of cyclopeptides with yields comparable to solution-based approaches without the need for high dilution of the reaction mixture and with significantly reduced reaction times and organic waste amount.