Antineoplastic agents. 400. Synthesis of the Indian Ocean marine sponge cyclic heptapeptide phakellistatin 2.
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.
Pettit
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GR
Cancer Research Institute and Department of Chemistry, Arizona State University, Tempe, Arizona 85287-2404, USA. bpettit@asu.edu
Rhodes
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MR
Tan
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D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000302:isolation & purification; D011161:Porifera / Q000737:chemistry*
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C119157:phakellistatin 2