| The chemistry of some marine sponges is discussed in this thesis. The sponge Halichondria sp. contains halichondramide, which is a highly effective antifungal and cytotoxic agent, and a potent inhibitor of feeding by the fish Thallasoma lutescens. Five related constituents were isolated from a large collection of Halichondria. The dorid nudibranch Hexabranchus sanguineus includes the sponge Halichondria sp. in its diet, and converts halichondramide into two related macrolides and concentrates these macrolides in their dorsal mantle, digestive gland, and egg masses. A Palauan sponge of the genus Cacospongia contained the sesterterpene suvanine, which is an inhibitor of the enzyme chlorinesterase. Suvanine is the first enol sulfate to be isolated and also contains a furan ring. A sponge of the family Halichondriidae collected from Scripps Canyon in La Jolla, California, contained halisulfate 1, a novel sulfated hydroquinone that showed in vitro antiviral and anti-inflammatory activity, and five new sulfated furans, halisulfates 2-6, that were related to suvanine. Some specimens of Luffariella variabilis contained the sesterterpenes luffariellin A and luffariellin B, which are potent inhibitors of the enzyme phospholipase A{dollar}sb2{dollar} (PLA{dollar}sb2{dollar}) and effective anti-inflammatory agents. Certain specimens of the nudibranch Chromodoris funerea contained the butenolides luffariellin C and luffariellin D. A Luffariella sp. sponge contained luffariellolide and luffolide, both of which are anti-inflammatory and are inhibitors of PLA{dollar}sb2{dollar}.; Oxidation of the furanoid metabolites of the sponge Dysidea sp. with singlet oxygen gave a suite of products that was identical to those isolated from some specimens of the nudibranch Chromodoris funerea that were feeding on the sponge. Treatment of a 3-substituted furan with singlet oxygen in the presence of a hindered amine base gave high yields of 3-alkyl-4-hydroxybutenolides. The 3-alkyl-4-hydroxybutenolides had in vivo anti-inflammatory activity. The structure activity relationships within this series of metabolites and the Luffariella metabolites, and the mechanism of inhibition of bee venom PLA{dollar}sb2{dollar}, are discussed in the final chapter. |
