Highly Efficient Synthesis of Covalently Cross-Linked Peptide Helices by Ring-Closing Metathesis

Olefin metathesis has been successfully applied to the synthesis of macrocyclic helical peptides [Eq. (a)]. Carbon-carbon bond tethers between amino acid side chains were introduced by ring-closing metathesis. This macrocyclization protocol is a novel and mild procedure for introducing nonnative covalent cross-links into peptide helices.