|Title:||Structural and Synthetic Studies of Potential Antitumor Natural Products|
|Degree:||Doctor of Philosophy|
|Committee Chair:||David G. I. Kingston|
|Committee Members:||Michael Calter|
|Harry C. Dorn|
|Keywords:||natural products, antitumor, sesquiterpenoid, furanonaphthoquinone|
|Date of defense:||August 13, 1998|
|Availability:||Release the entire work for Virginia Tech access only.
After one year release worldwide only with written permission of the student and the advisory committee chair.
Bioassay directed fractionation of the methyl ethyl ketone extract of Chiloscyphus rivularis yielded eight sesquiterpenoids, and detailed spectroscopic interpretation led to the assignment of their structures as 12-hydroxychiloscyphone, chiloscypha-2,7-dione, 12-hydroxychiloscypha-2,7-dione, chiloscypha-2,7,9-trione, rivulalactone, 4-hydroxy oppositant-7-one, chiloscyphone, and intermedeol. The structure and stereochemistry of rivulalactone, a novel trinorsesquiterpenoid, was confirmed by its synthesis starting from chiloscyphone. 12-Hydroxychiloscyphone, chiloscypha-2,7-dione, 12-hydroxychiloscypha-2,7-dione, chiloscypha-2,7,9-trione, rivulalactone are new. 12-Hydroxychiloscyphone showed selective bioactivity towards DNA repair-deficient yeast mutants and cytotoxicity to human lung carcinoma cells. In order to improve the activity of cytotoxic furanonaphthoquinones by affixing a hydroxyamino side chain, 2-methyl-2-[2'-(4',9'-dihydronaphtho[2',3'-b]furan-4',9'-dionyl methyl)amino]-1,3-propanediol and its analogs have been synthesized. Bioassay data showed they act by a different mechanism of action than their parental furanonaphthoquinone derivatives.
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