Solid-Phase Synthesis of Cyclic Octapeptide Phakellistatin 15

The total synthesis of a naturally occurring cyclic proline-enriched octapeptide phakellistatin 15, from a marine sponge, where all the amino acids are in L-configuration, was reported. The phakellistatin 15 was synthesized by applying a two-step solid-phase/solution synthesis strategy. The linear octapeptide was assembled by standard Fmoc chemistry on 2-chlorotrityl chloride resin, cleaved off-resin with acetic acid/trifluoroethanol/dichloromethane to keep the side-chain protecting groups intact, and subsequently cyclization was achieved by a solution method. The final product was purified by a preparative RP-HPLC system, and its structure was identified by HR-QTOF-MS, H-1 NMR, and C-13 NMR.