California Sea Grant College Program

Two areas of marine natural products were explored in this work. The young but established area of sponge natural products was investigated as a source of anticancer secondary metabolites. In addition, the newly emerging field of marine fungal natural products was studied to provide insight on the capacity of marine fungi to produce novel natural products. The possibility that marine fungi are a microbial source of sponge derived natural products was examined through chemical investigations of fungi cultured from sponges.

The chemical investigation of both the sponges and fungi was carried out with the modern techniques and methods of natural products chemistry. Sophisticated chromatographic and spectroscopic methods were employed for the isolation and characterization of all isolated natural products.

The four projects described in this thesis are presented in two parts. Chapters two and three describe the structures of plakortolide E and plakoric acid from a Plakortis species sponge and the structure of hipposulfate from a Hippospongia species sponge. The work on the Plakortis sp. sponge, chapter two. was initiated by whole cell cytotoxicity assays of slow growing melanoma tumor lines. The work on hipposulfate, chapter three, was initiated by a positive result in a matrix metalloproteinase enzyme assay. This enzymatic screening is a complimentary method to the whole cell assay method employed for the cytotoxic Plakortis sp. extracts.

Chapters four and five provide the details of the work on sponge derived marine fungal cultures. Chapter four discusses the young field of marine fungal natural products and provides a review of the sources and novelty of the compounds found to date in this new area. Chapter four also describes the first fungal project in this laboratory which yielded three new natural products, chloriolins A-C. Chapter five describes the structural elucidation of two novel compounds, asperizine and asperic acid, and the dereplication of three known secondary metabolites, malforrnin C, pyrophen, and hexylitaconic acid, from a sponge derived Aspergillus c.f. niger fungus.