Rimoldi, John M.2014-03-142014-03-141993etd-10102005-131622http://hdl.handle.net/10919/39739Several 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.xi, 250 leavesBTDapplication/pdfenIn CopyrightLD5655.V856 1993.R576Dissertationhttp://scholar.lib.vt.edu/theses/available/etd-10102005-131622/