Synthesis of Constrained Head-to-Tail Cyclic Tetrapeptides by an Imine-Induced Ring-Closing/Contraction Strategy

摘要

Head-to-tail cyclic peptides exhibit remarkable biological activities with extraordinary potency and oral-bioavailability owing to their compacted structures and high stability against enzymatic degradation and physical denaturation; thus, cyclic peptides have attracted a lot of attention in the pharmaceutical industry. In particular, cyclic peptides with small-sized rings have a drug-like scaffold that is ideal for therapeutic development. A range of cyclic tetrapeptides have been shown to exhibit a wide spectrum of biological activities, including the cytotoxic agents trapoxin and hirsutide, the opioid receptor-binding CJ-15208, the antiprotozoal apicidin, and the antifungal rhodopeptins.