Synthesis of cyclic peptides through direct aminolysis of peptide thioesters catalyzed by imidazole in aqueous organic solutions

A promising method for the synthesis of cyclic peptides through the direct aminolysis of peptide thioesters is presented. The cyclization step was carried out in a mixture of acetonitrile and 1.5 M aqueous imidazole solution with no observable oligomers. Studies on the N- and C-terminal residues show that the choice of C-terminal residue has a more significant effect on the success rate of cyclization than the choice at the N-terminal residue.