抄録
Linear acetylenes are prominent constituents of marine sponge of the order Haplosclerida. This class of metabolites was reported to exhibit potent cytotoxicity. During our search of bioactive compounds from marine invertebrates, the extract of a marine sponge Petrosia sp. collected at Miyako sea-knoll exhibited cytotoxicity against HeLa cells. Bioassay-guided fractionation of the extract afforded (-)-duryne (1), (-)-durynes B-F (2-6), and miyakosynes A-F (1-6). The structures of (-)-durynes were elucidated by NMR and tandem FABMS analyses. The positions of the olefinic bonds were confirmed by ozonolysis experiments, and the absolute configurations were determined by the modified Mosher's method. Compound 1 was found to be the enantiomer of duryne, a previously reported sponge metabolite. Miyakosynes A-F (7-12) were methyl branched linear acetylenes. Their structures were elucidated by a combination of spectroscopic analyses and chemical methods. The positions of the branched methyls were assigned by tandem FABMS analyses applying the simulations of the intensities of the fragment ions. The absolute configurations of the secondary alcohols at both termini were determined by the modified Mosher's method. (-)-Durynes exhibited cytotoxicity against HeLa cells with IC^<50> values between 0.08 and 0.50μM. (-)-Duryne (1) was equipotent to duryne, indicating that the cellular targets of these metabolites do not recognize the configuration of the secondary alcohols. Miyakosynes exhibited cytotoxicity against HeLa cells with IC^<50> values between 0.04 and 0.30μM. From these data, we reasoned that neither central olefin nor methyl branch is indispensable for the cytotoxicity of this class of metabolites.
