Synthesis of a paclitaxel isomer: C-2-acetoxy-C-4-benzoate paclitaxel

A synthesis of the C-2-acetoxy-C-4-benzoate paclitaxel 2 is described. This analog has the substituents at C-2 and C-4 transposed. The key steps in the synthesis include the sequential use of Red-Al as reducing agent for the regioselective reduction of the C-2 benzoate and the C-4 acetoxy within the baccatin core. Iso-paclitaxel 2 was considerably less potent than paclitaxel in tubulin polymerization and in vitro cytotoxicity assays.