West, Lyndon M.

Throughout history, natural products have produced a plethora of biologically active compounds that have established applications in medicine, biology, and pharmacy. The exploration for improved cytotoxic agents has continued to be a crucial path in natural products drug discovery. The focal point of this thesis sheds light on the biosynthetic relationship between the two distinct classes of briarane diterpenoids, the γ-lactone briarane and the briareolate esters. Additionally, this study elaborates on the discovery and elucidation of structurally unique secondary metabolites from the gorgonian coral Briareum asbestinum.
The first chapter of this thesis provides a review of the development and discovery of diverse
secondary metabolites. In addition, this chapter describes the role of natural products in drug discovery and summarizes the research progress in marine natural product chemistry in conjunction with a detailed overview of the current marine-derived pharmaceuticals.

The projects described in this dissertation concentrated on investigating Caribbean species for qualitative and quantitative chemical differences. Chapter one includes a brief update on the status of natural products as drugs, a discussion of the biodiversity of Caribbean marine organisms as well as a discussion about the chemistry of algae and sponges. In chapter two, an experiment to test for possible effects of warmer, more acidic water and how that will impact coral reef organisms was conducted. Six common Caribbean coral reef sponge species were grown in seawater for 24 days ranging from values experienced at summer-maxima (temperature = 28 ºC; pH = 8.1) to those predicted for the year 2100 (T = 31 ºC; pH = 7.8). For each species, attachment rates, growth, and survival were similar between temperature and pH levels. Only two metabolite concentrations varied significantly between treatments but were similar to baseline levels. In chapter three, a chemical survey of Florida Keys algae was performed using MeOH extraction and HP-20 SPE with varying Me2CO:H2O solutions. 1H NMR spectra were collected for each fraction and analyzed for interesting signals. A Laurencia sp. was extracted and found to contain the known compound isodactylyne (61) with the structure determined using spectroscopic analyses. In chapter four, a Laurencia obtusa specimen was investigated to determine the compound causing oxygenated signals between 4.50 – 4.80 ppm in the 1H NMR spectra observed in chapter three. A large scale extraction and fractionation was performed and the compound was determined to be 1-O-palmitoyl-2-O-myristoyl-3-O-(6-sulfo-α- D-quinovo-pyranosyl)-glycerol (63). In chapter five, the isolation and structural elucidation of a new compound, furocaespitanenone (64) and two known compounds (10R)- and (10S)-10-O-methylfurocaespitanelactol 65 and 66, from a Laurencia sp. collected off of the Florida Keys using MeOH extraction and HP-20 column chromatography is described. A potential biosynthesis of 64 from furocaepsitane (68) is proposed.