Complex cyclic peptide synthesis via serine/threonine ligation chemistry.

Non-ribosomal cyclic peptides are abundant in natural sources, exhibiting attractive bioactivities and favorable pharmacological properties. Furthermore, their structural complexity renders them as attractive synthetic targets. A general task for cyclic peptide synthesis is the peptide cyclization. Compared to the traditional dehydration-based peptide macrolactamization, chemoselective peptide ligation provides an alternative, sometimes advantageous, strategy to cyclize peptides. Herein, we provide a series of structurally complex cyclic peptide examples whose total syntheses were achieved via peptide ligation-mediated peptide cyclization. The special features of these strategies for achieving the total synthesis are highlighted.