Durynes G-I, antiproliferative polyacetylenes from Cribrochalina vasculum and their chlorinated decomposition products.

Bioassay-guided fractionation of the organic solvent extract of sponge Cribrochalina vasculum yielded three new linear asymmetric polyacetylenes, namely durynes G-I (3-5). Their structures were elucidated by combined spectroscopic and spectrometric techniques and the absolute configuration of the C-3 stereogenic center was determined via modified Mosher's ester methodology. The compounds were found to be unstable upon prolonged exposure to deuterated chloroform and gradually converted to multi-chlorinated analogues, whose structures were fully elucidated, and the mechanism of formation was proposed. In the NCI-60 cancer cell cytotoxicity panel, the new natural products showed potent antiproliferative activity with GI50 values in low micromolar ranges. Analogues with the addition of chlorine to the central olefin showed reduced cytotoxic activity, while the chlorination of the olefin of the alkenyl carbinol group was shown to diminish the activity of the scaffold.