Efficient synthesis of cysteine-rich cyclic peptides through intramolecular native chemical ligation of N-Hnb-Cys peptide crypto-thioesters

We herein introduce a straightforward synthetic route to cysteine-containing cyclic peptides based on the intramolecular native chemical ligation of in situ generated thioesters. Key precursors are N-Hnb-Cys crypto-thioesters, easily synthesized by Fmoc-based SPPS. The strategy is applied to a representative range of naturally occurring cyclic disulfide-rich peptide sequences.