Synthesis of 7 beta-sulfur analogues of paclitaxel utilizing a novel epimerization of the 7 alpha-thiol group

[GRAPHICS] 90 degreesC Paclitaxel analogues with a sulfur group at the 7 beta position were requir ed for SAR studies, Attempts to generate these compounds by displacing a 7 alpha leaving group with sulfur nucleophiles were unsuccessful. Instead, th ese compounds were successfully prepared from a 7 beta -thiol intermediate that was obtained by a base-catalyzed epimerization of the 7 alpha -thiol d erivative. The epimerization presumably proceeds through a thioaldehyde int ermediate and exhibits the opposite stereochemical preference of its oxygen counterpart.