Structural and Synthetic Studies of Bioactive Natural Products

As part of an ongoing investigation for anticancer agents from natural resources, four plant extracts were determined to contain interesting bioactivity. These extracts were separated by chromatography to afford a number of bioactive compounds that were characterized by spectral analysis. Fractionation of the fruit extract of Cryptocarya crassifolia led to the isolation of two known flavonoids and two known cryptocaryalactones. Fractionation of the bark extract of the same plant also gave the same two cryptocaryalactones. All these compounds were weakly active in a cytotoxicity assay. Two new isoflavones were isolated from the roots of an Egyptian lotus plant, Lotus polyphyllos. Both compounds were characterized by UV, NMR, and mass spectroscopic analysis The methanol extract from the leaves and bark of a Brexiella sp. were found to display significant cytotoxic activity versus the A2780 mammalian cell line. Two highly active cardenolides, glucodigimetholide and xysmalogenin glucoside, were isolated and found to be responsible for the bioactivities. Both compounds were characterized by spectroscopic analysis and comparison to the known literature data. Two marine extracts were also investigated. The pyridoacridine alkaloids, amphimedine and neoampimedine, were isolated from the marine sponge Petrosia sp., and three bromo-tyrosine alkaloids were isolated from the marine sponge Porphyria flintae. The structures of these known compounds were all elucidated by comparison to literature data. Two 6-amino-glycoglycerolipids had been previously isolated from a marine algae species and shown to inhibit the activity of the enzyme Myt-1 kinase. These compounds and some related compounds were synthesized and their bioactivities against Myt1 kinase were determined. Two isotopically labeled paclitaxel analogs (2D, 19F) were prepared in preparation for studies of the tubulin-binding conformation of paclitaxel by REDOR NMR. A new macrocyclic A-nor-paclitaxel was also synthesized, and was found to have good cytotoxicity and improved tubulin-binding activity as compared with paclitaxel.

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

2005

Author dc:creator

• Tang, Shoubin

Chair dc:contributor.committeechair

• Kingston, David G. I.

Committee members dc:contributor.committeemember

• Gandour, Richard D.
• Etzkorn, Felicia A.
• Carlier, Paul R.
• Dorn, Harry C.

• glycolipids
• synthesis
• isolation
• anticancer
• Natural Product
• paclitaxel

Statement dc:rights

• In Copyright

Licence dc:rights.uri

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

Dc Identifier Other

etd-02032006-160906

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/26104