Chemical investigations of endophytic and fungicolous fungi

Fungi continue to serve as valuable sources of a diverse variety of bioactive secondary metabolites, some of which have found applications as important pharmaceuticals and agrochemicals. Our research group employs an ecology-based strategy for the selection of fungi for chemical studies. The research described here involves chemical investigation of fungicolous and endophytic fungi that resulted in the isolation and identification of many new natural products, as well as some previously known metabolites. Mycoparasitic and fungicolous fungi are those that colonize other fungi, and are viewed as potential sources of antifungal agents because of the negative effects exerted on their hosts due to this colonization. Many antifungal compounds have been isolated by members of our research group from such fungi. Fractionation of the ethyl acetate extracts of cultures of thirteen fungal isolates, followed by characterization using various NMR and MS techniques, afforded fifteen new and twenty-six known compounds representing diverse structural classes. Some of these compounds showed antifungal and antiinsectan effects accounting for bioactivities originally observed for the crude extracts.

Endophytic fungi are those that inhabit host plants asymptomatically and may or may not cause disease after some time. Studies show that in some cases they may be beneficial to the host plant by providing protection against various pathogens or by improving the resistance of the host in some way. Such advantages may be due, at least in part, to the production of bioactive secondary metabolites by these fungi. Chemical investigations of seven crop endophytes led to the isolation and characterization of eleven new and twenty-eight known compounds. Some of these fungal known fungal metabolites exhibited antifungal, antimicrobial, and/or antiinsectan effects, and may therefore provide insight into the potential protective roles of the corresponding crop endophytes against plant pathogens or insect pests.

The fungal secondary metabolites isolated during the course of these studies represent a variety of biosynthetic classes, including peptides, polyketides, terpenoids, and compounds with mixed biogenetic origins. Details of the isolation, structure elucidation, and biological activity of these new compounds are presented in this thesis.

Structure elucidation was performed mainly by analysis of various MS and NMR data, although chemical derivatization reactions and/or X-ray diffraction analysis data were employed in some instances. Absolute configuration assignments were made using Mosher's method, X-ray crystallography, and/or by ECD spectral analysis in combination with computational analysis. Details of the isolation, structure elucidation, and biological activity of these new compounds are presented in this thesis.