Preparation of 'side-chain-to-side-chain' cyclic peptides by Allyl and Alloc strategy: Potential for library synthesis

Automated and manual deprotection methods for allyl/allyloxycarbonyl (Allyl/Alloc) were evaluated for the prepn. of side-chain-to-side-chain cyclic peptides. Using a std. Allyl/Alloc deprotection method, a small library of cyclic peptides with lactam bridges (with seven amino acids) was prepd. on an automatic peptide synthesizer. We demonstrate that the Guibe method for removing Allyl/Alloc protecting groups under specific neutral conditions [Pd(PPh3)4/PhSiH3/DCM] can be a useful, efficient and reliable method for prepg. long cyclic peptides on a resin. We have also manually synthesized a cyclic glucagon analog contg. 24 amino acid residues. These results demonstrated that properly controlled palladium-mediated deprotection of Allyl/Alloc protecting groups can be used to prep. cyclic peptides on the resin using an automated peptide synthesizer and cyclic peptides with a long chain