Recent progress on total synthesis of cyclic peptides

Cyclic peptides are composed of canonical and non-canonical amino acids in a rigid conformation, which endow them high binding affinity and specificity, proteolytic stability, and enhanced membrane permeation compared to linear analogs, thereby making them as promising therapeutics of the future. To date, more than 40 cyclic peptides from nature or derivatives are used as therapeutics, with an average of around one cyclic peptide drug approved per year. This review aims to highlight the past 5 years’ advances in total synthesis of cyclic peptides including monocyclic peptides, bicyclic peptides, and tricyclic peptides, laying a solidly synthetic foundation for drug discovery.