Structural and Synthetic Studies of Potential Antitumor Natural Products

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.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemistry

Department dc:contributor.department

Chemistry

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

1998

Author dc:creator

• Wu, Chongming

Chair dc:contributor.committeechair

• Kingston, David G. I.

Committee members dc:contributor.committeemember

• Gandour, Richard D.
• Dorn, Harry C.
• Calter, Michael A.
• Castagnoli, Neal Jr.

• natural products
• antitumor
• sesquiterpenoid
• furanonaphthoquinone

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

etd-72198-18137

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/30682