| Natural products have traditionally been a source of novel therapeutic agents. Clinically useful natural products such as penicillin, amphotericin, and taxol were derived from different organisms, and since their discovery, these organisms have been thoroughly examined. Our search for new, biologically active compounds is focused on the investigation of underexplored natural sources. Endophytic fungi--fungi that live in the intercellular spaces of plants--and insect-associated fungi are two such classes.;Through active collaboration with chemical ecologists and pharmaceutical companies, we have been able to study the bioactive constituents of a variety of fungi. Immunosuppressive compounds subglutinol A and B, cytochalasin E, and the T-2 toxin were obtained from the endophytic fungi of the Chinese plant Tripterygium wilfordii; a cholesteryl ester transfer protein inhibitor was isolated from an insect-associated fungus of the ant Pogonomyrmex badius; and, three phytotoxic compounds--pestalopyrone, hydroxypestalopyrone, and pestaloside--and two antimicrobial compounds trivially named torreyanic acid and taxifolic acid were obtained from an endophytic fungus of the rapidly declining tree Torreya taxifolia. Several of these structures are novel, and suggest that these fungal sources have potential value. This dissertation will discuss pharmaceutically-interesting compounds in chapters two and three, and in chapter four, describe fungal metabolites that play a role in the chemical interaction between a plant and microbe. |
