| Natural products chemistry is a vital field in the search for new pharmaceutical and agrochemical lead compounds. Numerous therapeutic agents have been discovered from natural sources, and the study of secondary metabolites has also led to the recognition of new pharmacophores. Fungi are renowned for their ability to produce bioactive molecules including important drug classes such as the penicillins, cyclosporins, and statins, yet many types of fungi remain relatively unexplored as sources of new biologically active natural products. In an effort to search for bioactive fungal metabolites in an efficient manner, the research described in this thesis employed an ecology-based approach to identify fungal isolates deemed likely to produce active compounds. Two niche groups were identified as targets for chemical investigation based on their unique ecology. Compounds were isolated from targeted fungi using various chromatographic techniques, and structures were characterized through analysis of 1D and 2D NMR spectroscopic data combined with information provided by mass spectrometry, chemical derivatization, physical and optical measurements, and/or X-ray crystallography.; Endophytic fungi live asymptomatically within plant tissues and have been shown in some instances to confer benefits to their host plants via production of bioactive secondary metabolites. Investigations of chemically unexplored corn endophytes led to the isolation and identification of six compounds, including four pyrrocidines (two of which were new). The pyrrocidines, which were obtained from multiple isolates of the common corn endophyte Acremonium zeae, displayed antifungal, antibacterial, and cytotoxic activities. These findings spurred the development of assays for their detection in corn kernels, in what is undoubtedly the first step of many in characterizing the role that A. zeae and the pyrrocidines may play in corn.; Fungicolous fungi colonize other fungal species. This ecological niche group includes fungi called mycoparasites which cause damage to and obtain their nutrients from the host fungus, as well as other fungal colonists whose roles are less well known. The damage often caused upon colonization of host fungi suggests that fungicolous fungi may commonly produce antifungal compounds. Chemical investigations of fungicolous fungi described in this thesis afforded 35 compounds of various structural types, 15 of which were new. |
