Gr. Pettit et al., Antineoplastic agents. 400. Synthesis of the Indian ocean marine sponge cyclic heptapeptide phakellistatin 2, J NAT PROD, 62(3), 1999, pp. 409-414
Solution-phase synthesis of the marine sponge constituent phakellistatin 2
(1), cyclo(Tyr-Pro-Phe-Prone-Ile-Pro), was completed using a combination of
stepwise coupling and (4 + 3) segment condensation. Use of diethyl phospho
rocyanidate 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 phakellist
atin 2 (1) depending on the method employed. The synthetic cyclic peptide w
as chemically but not biologically identical with the natural product.