Facile Synthesis of AM-Toxin II

In a search for a more effective synthetic route for AM-toxins (cyclic tetradepsipeptides), the syntheses of [l-Phe3]AM-toxin II as a preliminary peptide and AM-toxin II as a target were attempted. The cyclization of H–l-Ser(Bzl)-l-Ala–l-Hmb–l-Phe–ONSu (Hmb, 2-hydroxy-3-methylbutanoic acid) in pyridine gave a cyclic monomer in high yield (59%). The removal of O-Bzl in the cyclopeptide and a subsequent dehydration of Ser with carbodiimide–CuCl afforded [l-Phe3]AM-toxin II in 24% yield. AM-Toxin II was synthesized in similar yield as in the case of the analog. The characteristic features of synthetic AM-toxin II were identical to those of the natural one.