Chemical investigations of bioactive secondary metabolites from coprophilous and ascostroma-producing fungi

Interspecies competition (antagonism) has often been observed among fungal species that compete with each other in nature. One of the mechanisms involved in this competition is the production of antifungal agents. Based on these precedents, we have undertaken studies of antagonistic coprophilous (dung-colonizing) fungi as sources of new natural products with potentially valuable antifungal activity. These studies are guided by bioassays against early-successional competitor fungi, as well as the medically important yeast Candida albicans. In the present study, several new compounds were isolated from Coniochaeta spp. These results constitute the first reported chemical investigations of any member of the genus Coniochaeta. Two new benzoquinone derivatives were isolated from Podospora anserina. In addition, a number of known bioactive compounds, including three different types of peptides, were isolated from several other coprophilous fungal species. All of these compounds displayed significant antifungal and/or antibacterial activity.; Sclerotia and ascostromata are important physiological structures produced by certain fungi for propagation and survival. The observation that these fungal bodies resist insect predation suggests that they may have evolved chemical defenses. As an extension of our ongoing investigation of fungal sclerotia as sources of antiinsectan metabolites, ascostromata from members of the genus Eupenicillium were examined chemically. Two aflavinine analogs were isolated from E. crustaceum ascostromata. This compound-type was previously known only from sclerotia of Aspergillus spp. The major aflavinine analog was found to be present in the ascostromata at a level that causes significant feeding reduction by the fungivorous beetle Carpophilus hemipterus. Additional studies clearly indicated that these aflavinine analogs are concentrated in the ascostromata. Other isolates of E. crustaceum were also investigated. During these studies, several novel bioactive compounds of peptide and terpenoid/polyketide origin were isolated from E. molle. Structures of the isolated compounds were determined by spectroscopic techniques, especially high field 2D-NMR methods. Details of the isolation, structure elucidation, and bioactivity of these compounds are presented in this thesis. These results support the strategy of using ecological evidence as a guide to the discovery of new, potentially valuable bioactive fungal metabolites.