This thesis describes investigations of marine algal secondary metabolites, with particular interest in their biomedical and agrichemical potential. Invaluable in such pursuits have been the access and application of advanced spectroscopic techniques, such as NMR, and the ability to assess the biological activity of the algal samples in a variety of diverse protocols, through in-house evaluation and industrial collaborations. As an in-house bioassay, a survey of algal extracts for molluscicidal activity has led to the isolation of the previously reported chondrocole C (Portieria hornemanni), tanikolide (Lyngbya majuscula), and debromoaplysiatoxin (L majuscula). Debromoaplysiatoxin is 100 times more potent than niclosamide, the commercially utilized molluscicide. Such activity may make debromoaplysiatoxin an attractive agent for molluscan biological control to prevent the spread of schistosomiasis in artificial waterways such as irrigation channels and rice paddies. The isolation of chondrocole C led to further chemical investigations of P. hornemanni. A total of six related polyhalogenated monoterpenes were isolated from this collection. While four of these compounds were previously reported, taviochtodene represents the newest member of this class of secondary metabolites. Previously, this alga has yielded compounds with great potential anticancer utility, but naturally and synthetically elusive. The discovery of this class of chemistry potentially locates new geographic territory to search for such anticancer metabolites. While there has been little reported biological activity attributed to the malyngamides, they form the most prevalent class of secondary metabolites isolated from Lyngbya majuscula. To this list we have added malyngamides L, Q, and R. Of particular note, malyngamides Q and R were the first malyngamides to have been reported with altered stereochemistry at the vinyl chloride carbon. Subsequently, and in part stimulated by this finding, this alternate stereochemistry has been defined for some newly reported malyngamides. Also from L majuscula, tortugin and lyngbyabellin B were isolated as toxic cyclic depsipeptides. Both of these compounds displayed relatively potent biological activity (brine shrimp and antifungal). Each possessing particular structural motifs previously seen in invertebrate secondary metabolites, they lend further evidence for cyanobacteria as the producer of many of the polyhalogenated compounds often attributed to de novo invertebrate biosynthesis. / Graduation date: 2002

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2006. / Includes blibliographical references.

This thesis is an account of my explorations into the field of natural products chemistry. These investigations led to the discovery of several novel secondary metabolites isolated from the marine cyanobacterium Lyngbya majuscula. In addition, biosynthetic investigations were undertaken using stable isotope-labeled precursors. The dominant role that NMR spectroscopy plays in the field of natural products chemistry has led to the development of several novel pulse sequences. Hectochlorin was discovered during a phytochemical investigation of a cultured L. majuscula originally collected off the coast of the Caribbean Island, Jamaica. The absolute stereochemistry was determined by X-ray crystallography. Through a series of biological evaluations, this compound was found to stimulate actin polymerization. The jamaicamide class of compound was isolated from the same organism that yielded hectochlorin. The structures were elucidated utilizing a variety of NMR methods, including a newly developed pulse sequence. Because the producing organism was in culture, a biosynthetic pathway investigation ensued to elucidate the carbon framework in jamaicamide A. The marine natural product barbamide is intriguing due to the incorporation of a trichloromethyl group into its molecular constitution. Further investigation into the timing of the chlorination reaction has been pursued. In addition, the isolation of dechlorobarbamide and the determination of the absolute stereochemistry assignment of barbamide was accomplished. A reevaluation of the stereochemistry of antillatoxin necessitated a correction in the original assignment. Four antillatoxin stereoisomers were obtained from a collaborator and found to possess differing levels of biological activity. The three dimensional solution structures of these isomers were evaluated in an effort to understand the role these stereochemical features play in the observed bioactivity. The structures were determined utilizing NMR-derived constraints applied to molecular modeling calculations. The development of two new pulse sequences for the determination of long-range heteronuclear coupling constants was also accomplished. The 1,1 ADEQUATE experiment was modified to yield an ACCORDIAN experiment which can be optimized to observe of a wide range of ��J[subscript cc] couplings. This new experiment is demonstrated for a model compound as well as for the new marine natural product jamaicamide A. / Graduation date: 2002

My investigations of the natural products of marine algae have resulted in the discovery of several new secondary metabolites. Bioassay-guided fractionation led to the isolation of these new compounds and spectroscopic analysis was utilized in their structural characterization. Two new and potent antimitotic metabolites, curacins B and C, were isolated from a Curacao collection of Lyngbya majuscula. In addition, four curacin A analogs were prepared by semisynthetic methods. The structures of the new curacins and the curacin A analogs were determined by spectroscopic analysis in comparison with curacin A. The biological properties of the new natural products and synthetic derivatives of curacin A were examined. Investigations of another Curacao collection of L. majuscula revealed a new cytotoxic lipopeptide, microcolin C. Microcolin C was found to have an interesting profile of cytotoxicity to human cancer-derived cell lines. A new metabolite, vidalenolone, was isolated from an Indonesian red alga Vidalia sp. The structure of this new cyclopentenolone-containing compound was determined by a combination of spectroscopic methods. Filamentous cells isolated from female gametophytes of the brown alga Laminaria saccharina were cultured in flasks or bioreactors. These cultures produced a variety of w6-lipoxygenase metabolites: 13-hydroxy-9,11-octadecadienoic acid (13-HODE), 13-hydroxy-6,9,11,15-octadecatetraenoic acid (13-HODTA), and 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE). Five oxidized anandamide derivatives were prepared from anandamide through autoxidation in an exploration of ligand binding to the cannabinoid receptor. Their structures were determined by a combination of NMR spectroscopy and GC-MS. The cannabinoid receptor binding affinity of these derivatives was evaluated. This study revealed the following trend in activity: anandamide > 15- > 9- > 8- > 11- > 5-hydroxyanandamide. / Graduation date: 1998

Marine algae have been recognized as a rich resource of new and unusual organic molecules with diverse biological properties. The current need to develop new antifungal, anticancer, antibiotic and antiviral drugs has led to an intense research effort into the discovery, isolation and structure determination of potential medicinal agents from marine algae. In the past two years, I have participated in a drug discovery program designed for antitumor, antifungal and other agents of potential pharmaceutical utility from the marine cyanobacterium Lyngbya majuscula. This research utilized modern chromatographic and spectrochemical techniques including 2D NMR spectroscopy. Brine shrimp toxicity guided the fractionation that led to the discovery of the biologically active compound kalkitoxin from a Curacao Lyngbya majuscula extract. The structure of this new thiazoline ring-containing lipid was determined spectroscopically by interpretation of 2D-NMR experiments, including heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple-bond coherence spectroscopy (HMBC) and ��H-��H COSY at room temperature and elevated temperature. Kalkitoxin shows modest molluscicidal toxicity, good brine shrimp toxicity and extremely potent ichthyotoxicity. From the same extract of Lyngbya majuscula, I also isolated two other secondary metabolites, malyngamide J and malyngamide L. The structures of these new compounds, including stereochemistry, were determined by spectroscopic techniques including 2D-NMR experiments and by comparison with other known malyngamides. / Graduation date: 1997

Thesis (Ph.D.) - James Cook University, 2007. / Typescript (photocopy) Bibliography: leaves 183-195.

Graduation date: 2003

Graduation date: 1998

Thesis (Ph. D.)--University of Canterbury, 2007. / Typescript (photocopy). Includes bibliographical references. Also available via the World Wide Web.

Thesis (M.Sc.). / Written for the Dept. of Plant Science. Title from title page of PDF (viewed 2008/07/29). Includes bibliographical references.