Antineoplastic Agents. 400. Synthesis of the Indian Ocean Marine Sponge Cyclic Heptapeptide Phakellistatin 2^,1a

Abstract

Solution-phase synthesis of the marine sponge constituent phakellistatin 2 (1), cyclo(Tyr-Pro-Phe-Pro-Ile-Ile-Pro), was completed using a combination of stepwise coupling and (4 + 3) segment condensation. Use of diethyl phosphorocyanidate for the peptide bond formations gave the linear heptapeptide in 54% yield. Cyclization was achieved in high yields utilizing TBTU (2), BOP-C1 (3), PyBroP (4), and HOAt (5), resulting in 50-65% yields of phakellistatin 2 (1) depending on the method employed. The synthetic cyclic peptide was chemically but not biologically identical with the natural product.