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Many years of study have revealed that fungi are excellent sources of novel bioactive secondary metabolites. Some of these secondary metabolites possess therapeutic qualities that improve the quality of life for millions of people. Such metabolites include well known classes such as the penicillins, cephalosporins, and statins, yet many fungi remain underexplored as sources of biologically active metabolites. The research described in this thesis employs an ecology-based approach to targeting fungi for chemical investigation, and describes studies of fungi from two niche groups, fungicolous/mycoparasitic and endophytic fungi, as possible sources of new secondary metabolites with biological activities. In a parallel project, the structures of bioactive compounds isolated from peanut seeds that had been subjected to fungal attack were elucidated in the pursuit of compounds with beneficial bioactivities.
Mycoparasitic fungi are those that colonize other fungi by parasitizing the host, often leading to damage to the host fungus. Fungicolous fungi are those that colonize other fungi, but have not been proven to be true mycoparasites. The damage often caused by colonization of host fungi indicates that mycoparasitic and fungicolous fungi can produce antifungal compounds. Chemical investigations of such fungi described in this thesis afforded 37 compounds of various biosynthetic types, seven of which were new. Many of these compounds show antifungal, antimicrobial, and/or cytotoxic effects. Endophytic fungi live asymptomatically within plant tissues and in some cases may provide benefits to the host plant through the production of secondary metabolites. Chemical investigations of corn, wheat, and sorghum endophytes led to the isolation and characterization of 21 compounds, seven of which were new. Many of the endophyte metabolites encountered in this work showed antifungal, antimicrobial, and/or cytotoxic effects. The compounds isolated from peanut seeds were produced in response to fungal attack by an Aspergillus caelatus strain. All of these compounds were stilbene-derived phytoalexins, which are considered to be inducible chemical defenses whose production is elicited or enhanced upon microbial attack. Further studies of these newly identified compounds and their production could lead a a better understanding of how the plant defends itself. Such knowledge could enable researchers to manipulate this mechanism to obtain greater peanut resistance to invasion by pests. Additionally, the health benefits from related stilbene-derived compounds (e.g. resveratrol) from peanuts and other plants have been widely established. Knowledge about the presence of compounds of this type could add to the importance of peanut crop production. The compounds identified in this work were isolated using multiple chromatographic techniques, and the structures were established based on analysis of 1D and 2D NMR data combined with MS, chemical derivatizations, and/or optical measurement data. Absolute configuration assignments were achieved by application of Mosher's Method, CD spectral analysis, and/or chemical derivatizations. Details of the isolation, structure elucidation, and biological activity of these compounds are presented in this thesis.