UC San Diego

The partnership between natural products and synthetic organic chemistry date back to the origin of organic chemistry itself. While natural products became a major driving force for the development of novel organic reactions and synthetic strategies, organic synthesis has contributed in many ways to the elucidation and confirmation of structure, pharmaceutical development, and biosynthetic studies of natural products. Due to the recent advances in both of these two disciplines, there are new opportunities and issues surrounding natural products that organic synthesis can be applied to, and such studies comprise this dissertation. Chapter I introduces the background information and rationale for the dissertation research, which is based on the history of organic chemistry and newly emerging research topics in natural products chemistry. Chapter II describes the isolation, characterization, and toxicological evaluation of polybrominated diphenyl ethers from a mixed assemblage of a marine red alga and cyanobacteria. Chapter III describes the isolation, characterization, and biological evaluation of a novel vinylchloride-containing fatty acid, credneric acid, from a Lyngbya sp. Chapter IV describes the conception of a method for determining the absolute stereochemistry of natural products lacking proper functional groups for derivatization. This methodology was applied to a cyclopropane-containing fatty acid and resulted in a conflict with newly published literature, which is discussed in detail. Chapter V describes the development of an expedient and efficient total synthesis of a novel alkaloid, epiquinamide, isolated from the skin of a rainforest frog, Epipedobates tricolor. This work contributed to clarifying the identity of a potent and selective nicotinic receptor agonistic activity observed in the extract of E. tricolor. Chapter VI describes the development of a total synthesis of a marine cyanobacterial metabolite, somocystinamide A, which has been shown to be a potent inhibitor of endothelial cell proliferation and angiogenesis. The synthesis was later modified for scalability to meet the need for further pharmaceutical investigations of this important natural product. Chapter VII describes the synthetic investigations on scytonemin, a cyanobacterial metabolite possessing UV-blocking properties. Through this work, many intriguing insights into the biosynthesis of the natural product were obtained. Finally, Chapter VIII provides the conclusions drawn from this dissertation research.