The chemical synthesis of C-ring aryl taxoids

We designed and targeted for synthesis the C-ring aryl taxoids 2a-c in order to develop methods for the construction of the taxoid skeleton and to test their cytotoxicity against tumor cells. Compound 2a was synthesized by a convergent route from hydrazone 5 and aldehyde 4. Key steps included a Shapiro reaction to join 5 and 4, a McMurry coupling to construct the 8-membered ring, a carbonate opening to introduce the 2-benzoate group, and an allylic oxidation followed by side-chain attachment. A similar sequence led to compound 2c, whereas attempts to attain 2b were thwarted by the lability of the benzyl group during the carbonate opening. The biological activity of 2a and 2c against tumor cells was considerably less than that of taxol.