UC San Diego

This dissertation describes the structure determination and biological activity of four groups of sponge derived secondary metabolites by integrated approaches using synthesis and circular dichroism. Chapter 2 describes the isolation and structure determination of brominated ene- yne tetrahydrofuran fatty acids, mutafurans A-G from the marine sponge Xestospongia muta. Two optically active ene- yne tetrahydrofuran model compounds were synthesized for chiroptical comparison to the natural product. Ene-yne and diyne alcohols and their corresponding naphthoate derivatives were synthesized for chiroptical studies. The antifungal activity of mutafurans A-G is reportedChapter 3 describes the identification of the feeding deterrent chemotype in the marine sponge Phorbas amaranthus against the common bluehead wrasse, Thalassoma bifasciatum. Two types of sulfated sterols were isolated from the highly deterrent polar extracts: amaranzoles A-F and amaroxocanes A and B. The structure determination of amaranzoles A and B was assisted by synthesis of optically active hydroxy- phenyl imidazole model compounds for comparison of NMR and CD to the natural products. Amaraoxocane B showed feeding deterrent activity against Thalassoma bifasciatum at higher than natural concentrations. Chapter 4 describes the identification of bis-piperidine alkaloids, xestoproxamines A-C from the marine sponge Neopetrosia proxima. The stereochemistry of the C23 methyl group in xestoproxamine C was elucidated by a Hoffman degradation/ cross metathesis protocol and comparison to an optically active model. A method was established to assign the absolute configuration of the bis-piperidine core in xestoproxamines A-C by chemical conversion to bis-p- bromophenacyl quaternary ammonium salts, and interpretation of the resulting ECCD spectra. The cytotoxic activity for xestoproxamines A-C is reported. Chapter 5 describes the isolation and structure determination of mollenyne A from Spirastrella mollis. The complete stereostructure was determined by a combination of NMR, CD, and chemical conversion. The biological activity for mollenyne A is reported