Synthesis of 7β-Sulfur Analogues of Paclitaxel Utilizing a Novel Epimerization of the 7α-Thiol Group

Paclitaxel analogues with a sulfur group at the 7β position were required for SAR studies. Attempts to generate these compounds by displacing a 7α leaving group with sulfur nucleophiles were unsuccessful. Instead, these compounds were successfully prepared from a 7β-thiol intermediate that was obtained by a base-catalyzed epimerization of the 7α-thiol derivative. The epimerization presumably proceeds through a thioaldehyde intermediate and exhibits the opposite stereochemical preference of its oxygen counterpart.