Marine natural products from sponges and deep water, marine-derived fungi

The following dissertation describes several investigations of marine natural products obtained from shallow water sponges and deep water fungi. Five chapters are presented, including an introductory chapter, two chapters relating sponge-derived compounds, and two chapters recounting deep water fungal-derived compounds. Chapter 1 begins with a detailed account of marine-derived, and marine-inspired, compounds currently in anti-cancer clinical trials. It describes the need for further discoveries of novel, bioactive marine natural products and offers some historical perspectives regarding this field of study. Bioassay/LCMS guided fractionation and dereplication concepts are introduced and an investigation of psammaplins from the sponge Pseudoceratina purpurea provides an example of their utility. Finally, an introduction to marine-derived fungi, with an emphasis on deep water collections, is offered. Chapter 2 is an analysis of phakellin alkaloids, and describes two novel N-methylated bromophakellins isolated from an Agelas sp. sponge from Papua New Guinea. Absolute stereochemistry was accomplished via 2D NOE NMR studies. Chapter 3 describes the chemical analysis of two Dysidea herbacea sponges as part of a larger study to examine the biosynthetic origins of the polychlorinated compounds identified. Bioactivity in a lipoxygenase assay showed that (-)-herbasterol is an activator, while (-)-neodysidenin is a moderately selective inhibitor. Chapter 4 represents results from the first account of novel marine natural products from deep water, marine-derived fungi cultured in saltwater. The structures of five new anserinone analogs are presented from a mixed culture of Penicillium fungi obtained from sediment collected at -4,380 feet in Fiji. These include the functionally dense epoxyserinones, which show low cytotoxicity against various human and murine cell lines. Chapter 5 discusses the status of deep water, marine-derived research, and supplies details regarding the UCSC deep water fungal libraries. The identification of several peptaibols from deep water Trichoderma sp. fungi is conferred. The identification of a novel tyrosol carbamate from an Arthrinium sp. fungus collected at -1800 feet using a portable, deep water collecting device is also illustrated.