Investigations of the chemistry of taxol

Abstract

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.