Abstract
dc:description.abstractSeveral C-7 and C-13 diazirinyl taxol analogs have been synthesized as potential photoaffinity-labeled derivatives for studying the nature of the binding site of taxol on polymerized tubulin. One analog has been prepared in both deuterium- and tritium-labeled versions. Methods were developed to selectively hydrolyze the C-2 benzoate of taxol which have allowed for the preparation of a variety of C-2 modified taxol derivatives. The C-2 taxol analogs were tested in several cell culture assays, and substantial increases in potency were observed with many of these derivatives, suggesting that the C-2 benzoate may play a crucial role in taxol's activity. Reaction of 2'-tert-butyldimethylsilyl-7-triethylsilyl taxol with Triton B™ selectively hydrolyzed the C-2 benzoate and the C-4 acetate respectively. This is the first disclosure of the C-4 deacetylation of taxol carrying an intact C-13 side chain. Several oxetane ring opened taxol analogs were synthesized via reaction of taxol with electrophilic reagents. The reaction of these oxetane ring-opened analogs have revealed some interesting rearrangements and functional group transfer reactions.
Degree
thesis:*- 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
- 1993
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Rimoldi, John M.
- Chair dc:contributor.committeechair
-
- Kingston, David G. I.
- Committee members dc:contributor.committeemember
-
- Castagnoli, Neal Jr.
- Merola, Joseph S.
- Mason, R.W.
- Hudlicky, Tomas
Rights
dc:rights- Statement dc:rights
-
- In Copyright
- Licence dc:rights.uri
- Language dc:language.iso
- en
Identifiers
dc:identifier.*- Dc Identifier Other
- etd-10102005-131622
- OAI identifier oai:identifier
- oai:vtechworks.lib.vt.edu:10919/39739