Total syntheses of (+)- and (-)-cacospongionolide B, cacospongionolide e, and related analogues. Preliminary study of structural features required for phospholipase a2 inhibition.

The total syntheses of the antiinflammatory marine sponge metabolites (+)-cacospongionolide B and E are described. The pivotal steps in the synthetic route include a three-step sequence that couples the two main regions of the natural product, as well as generates the side chain dihydropyran ring. The activity of the synthetic analogues against bee venom phospholipase A2 suggests that the cacospongionolides have enantiospecific interactions with the enzyme that may be independent of the gamma-hydroxybutenolide moiety. Copyright 2004 American Chemical Society