Investigations of the chemistry of taxol
| Autor: | Rimoldi, John M. |
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| Jazyk: | angličtina |
| Rok vydání: | 1993 |
| Předmět: | |
| Druh dokumentu: | Dissertation |
| Popis: | Several 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. Ph. D. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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