Studies on the chemistry of taxol

The novel diterpenoid taxol isolated from the western yew Taxus brevifolia is one of the most important lead compounds to emerge from the search for anticancer agents from plants. It shows consistent clinical activity against ovarian cancer and may also be active against other cancers. In this study, the preparation of various taxol derivatives was investigated, with the objective of better understanding the structural requirements for activity in the taxol series. The 7-hydroxyl group of taxol was derivatized with a photoaffinity label and other reagents as a beginning of the project to understand the interaction of taxol and tubulin, and the activity of all the derivatives in a tubulin assay was determined. A study of the deacylation and reacylation reactions of baccatin 111 was carried out in order to find conditions suitable for the preparation of 2-debenzoylbaccatin Ill , and thus 2-debenzoyltaxol. Finally, the reactions of taxol with various electrophilic reagents were investigated, and the structures of products with an opened oxetane ring and/or contracted ring A were determined. Biological assay results are reported on many of the compounds in this investigation.

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

1992

Author dc:creator

• Samaranayake, Gamini S.

Chair dc:contributor.committeechair

• Kingston, David G. I.

Committee members dc:contributor.committeemember

• Bell, Harold M.
• Dorn, Harry C.
• Hudlicky, Tomas
• Hanson, Brian E.

Statement dc:rights

• In Copyright

Licence dc:rights.uri

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

Language dc:language.iso

en

Dc Identifier Other

etd-10102005-131550

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/39708