Structure elucidation of novel natural products: Oppositines, eudistomides, spheciosterol sulfates, and fibrosterol sulfates

The studies presented in this dissertation are concerned with the isolation, structure elucidation, and biological evaluation of novel natural products from both marine and terrestrial sources. Under-explored regions of the natural environment represent an infinite source for the discovery of biologically validated, diverse natural products with therapeutic potential. Chapter 1 begins with a historical background of natural products and presents the rationale for studying their unique properties. The challenges of natural product discovery are continually being surmounted by advances in technologies. The latter part of Chapter 1 focuses on technological developments that facilitate structure elucidation, with a particular emphasis on advances in nuclear magnetic resonance (NMR).;A detailed investigation of the chemical constituents present in the plant Pleurostylia opposita, collected in Sri Lanka, resulted in the isolation of oppositines A and B; two new sesquiterpene pyridine alkaloids. The isolation, structural characterization, and biological activities of the oppositines are described in Chapter 2.;Eudistomides A and B, two new cyclic lipopeptides, were isolated from the ascidian Eudistoma sp., collected in the Fijian islands. These five-residue cystine-linked cyclic peptides are flanked by a C-terminal methyl ester and a 12-oxo- or 12-hydroxytetradecanoyl moiety. Chapter 3 details the isolation, complete structural characterization, and synthesis of the eudistomides.;The chemical composition of the sponge Spheciospongia sp., collected in the Philippines, was evaluated for the presence of PKCzeta inhibitors. This evaluation led to the isolation of three new sulfated sterols, spheciosterol sulfates A-C, as well as the known compound, topsentiasterol sulfate E. The isolation, structure elucidation, biosynthesis, and biological activity of the spheciosterol sulfates and topsentiasterol sulfate E are presented in Chapter 4.;As part of a continuing search for PKCzeta inhibitors, the unexplored sponge Lissodendoryx (Acanthodoryx) fibrosa, collected in the Philippines, was investigated. Consequently, two new sulfated sterol dimers, fibrosterols A and B, were isolated. Chapter 5 highlights the isolation, structure elucidation, and biological activity of the fibrosterols.;Chapter 6 presents a summary of the works presented in this dissertation, and highlights the two different approaches that were utilized to discover new compounds from both terrestrial and marine sources.