| Microbial secondary metabolites continue to serve important roles as pharmaceuticals, agrochemicals, and leads thereto. Although most studies in search of new microbial metabolites involve random screening of uncharacterized isolates, it is possible to employ an alternative approach involving ecological considerations. In many cases, interactions among fungi in natural ecosystems involve the production of a chemical agent by one species that exerts negative effects on another. The research described here involves ecology-based investigations of mycoparasitic, and coprophilous fungi as potential producers of novel metabolites with practical value.; Mycoparasitic fungi act as parasites of others, and the host species often suffers negative effects from this interaction. In some cases, these effects are caused at least in part by antifungal agents produced by the mycoparasite. Based on this observation, we have initiated studies of fungi that attack and/or colonize sclerotia and other long-lived fungal bodies as sources of new antifungal natural products. Our initial work in this area has focused on colonists of Aspergillus sclerotia as potential sources of anti-Aspergillus agents. Several colonist species afforded bioactive metabolites representing a variety of compound classes. For example, bioassay-guided fractionation of organic extracts from cultures of Podospora curvicolla and Phialophora bubakii led to the isolation of three new gamma-lactones, five novel cyclic depsipeptides, and four unprecedented metabolites of mixed biogenetic origin.; Reports of interspecies antagonism among coprophilous fungi led us to investigate such species as potential sources of antifungal agents. Chemical studies of coprophilous fungi have been limited, primarily because they are not commonly encountered in soil samples typically used as sources of microorganisms for screening programs. Our previous work in this area has resulted in the isolation of a variety of new, structurally interesting natural products. During these ongoing studies, a variety of new bioactive secondary metabolites were isolated from Nigrosabulum globosum, Podospora decipiens, Podopsora pleiospora, and Podospora communis.; The structures of these secondary metabolites were established by analysis of MS, NMR, and/or X-ray diffraction data. Details of the isolation, structure elucidation, and biological activity of these compounds are presented in this thesis. |
