California Sea Grant College Program

The following thesis presents results from several investigations of marine natural products. It is divided into 5 chapters consisting of an introduction, three chapters examining the metabolites of tropical sponges. and a final chapter which discusses the chemical profile of a marine derived fungal culture. Chapter 1 is a brief survey of some of the most promising bioactive marine metabolites discovered to date. Furthermore, the first chapter includes some history and perspective pertaining to the field of marine natural products and natural products in general. Chapter 2 is an analysis of sponge metabolites derived from several Indo-Pacific collections of Diacarnus cf spinopoculum. A series of new terpenes of the nuapapuin class (norditerpene peroxides) and muqubilin class (norsesterterpene peroxides) were isolated, along with the new dinorditerpenone muquketone. When these and other related isolates were screened for in vitro cytotoxicity, the diterpenes nuapapuin A methyl ester and nuapapuin 8 displayed selective behavior and thus were selected for in vivo evaluation. Chapter 3 is divided into two parts both involving the processing of organisms which contained small alkaloids. Part I details the study of Clathria basilana from which no chemistry was previously published. Five specimens were examined, but only one was found to contain the unique quinolizine, clathryimine A. When heated, this compound gave rise to the degradation product clathryimine B. Part 2 describes the isolation of phenethylguanidine analogs, the dihydrotubastrines, from a zoanthid-infested specimen of Petrosia cf. comignata. The dihydrotubastrines are the first examples from this compound class with a saturated acyclic C2 unit. Chapter 4 recounts the isolation of the new C 15-ketosterol haliclostanone sulfate along with the fairly common sterol metabolite halistanol sulfate from a Haliclona sp. Interesting and rare features of the new sterol include the cis-C/D ring junction and the sidechain. Chapter 5 is a discussion of two vertinoid polyketides isolated from a saltwater culture of Trichoderma longihrachiatum procured from a marine sponge. The new metabolite epoxysorbicillinol is described, and its absolute stereochemistry is determined from CD exciton coupling. Furthermore, biosynthetic analysis is used to infer the absolute stereochemistry of the known vertinoid bislongiquinolide.