Synthesis of phakellistatin 11: A Micronesia (Chuuk) marine sponge cyclooctapeptide

The cyclic octapeptide phakellistatin 11 (1), a constituent of The Federate d States of Micronesia (Chunk) marine sponge Phakellia sp., was synthesized using solid-phase techniques. An initial solution-phase synthesis proved t o be inadequate owing to spontaneous deprotection of the Fmoc group at the heptapeptide stage. Using the PAL resin attachment and proceeding from Fmoc -Glu-alpha -allyl ester, linear elongation of the octapeptide was performed until the final unit Pro was added. The allyl ester was removed using Pd-o [P(C6H5)(3)](4). Cleavage of the final Fmoc group and cyclization with PyA OP provided phakellistatin 11 (1) in 17% overall yield. The synthetic speci men of phakellistatin 11 (1) was found to be chemically but not biologicall y cancer cell lines) identical to the natural product. The result suggested a conformational difference or more likely the presence of a trace amount of a highly active antineoplastic agent that binds noncovalently to the nat ural cyclic octapeptide 1.