| The studies presented in this thesis investigated the use of filamentous fungi in combination with chemistry to provide novel routes to the family of diterpenes isolated from the Chinese herbal plant, Tripterygium wilfordii. The isolated diterpene triepoxides, triptolide (2) and tripdiolide (3), which represent the first reported natural products containing the 18 (4-;The substrates 45, 86 and 12 were obtained in gram quantities via stepwise syntheses from dehydroabietic acid (42). These compounds were incubated with liquid cultures of the fungi Syncephalastrum racemosum (UBC;The major product (35%) of the oxidation of triptophenolide (12) by C. elegans resulted from the hydroxylation of the aromatic ring C which produced the 11,14-diphenolic metabolite; the latter rapidly converted to the corresponding 11,14-triptoquinone (114). Subsequent studies were performed to optimize the production of 114 by C. elegans using factorial design. The effects of medium composition and biotransformation time on triptoquinone (114) production were evaluated. Statistical analysis of the experimental data predicted 71% yield of triptoquinone (114) at optimum conditions which was verified by experiment (70% yield). |
