Chemical investigations of freshwater and fungicolous fungi

Fungi are well-known to produce a tremendous variety of bioactive secondary metabolites which play important roles as pharmaceuticals and agrochemicals. In contrast to random-screening approaches utilized in industry, our research applies ecology-based strategy to the selection of fungi for chemical studies. The research described here involves the chemical investigation of freshwater and fungicolous fungi as producers of novel metabolites with potential practical value.

Freshwater fungi, as a distinctive ecological group, have only recently been studied in any depth, and remain underexplored in comparison with other fungal niche groups. Chemical studies of freshwater fungal isolates in our research group have led to the discovery of a variety of new bioactive metabolites, suggesting significant untapped potential among these organisms. Studies in this area described in this thesis led to the discovery of twenty-two new metabolites, many of which display significant antibacterial and/or antifungal activities. Some of these compounds possess novel structural features, such as new ring systems.

Mycoparasitic and fungicolous fungi are those that colonize other fungi and could be viewed as potential producers of antifungal agents because of the negative effects they often exert on their hosts. Bioassay-guided fractionation of extracts from cultures of selected mycoparasitic and fungicolous fungal isolates afforded twenty-five new compounds representing diverse structural types. Most of these compounds display biological activity, with some showing antifungal and/or antiinsectan effects.

The new secondary metabolites isolated during these studies represent a variety of different biosynthetic classes, including cyclic depsipeptides, nucleosides, polyketides, macrolides, terpenoids, and compounds with mixed biogenetic origin. Their structures were established by analysis of MS and NMR data, chemical degradation or derivatization reactions, and/or X-ray diffraction analysis data. Absolute configuration assignments were achieved by application of different strategies, such as Mosher's method, Marfey's method, or CD spectral analysis. Details of the isolation, structure elucidation, and biological activity of these new compounds are presented in this thesis.