A series of heterocyclic taxanes were synthesized and evaluated to investigate structure activity relationships at the 2-position of paclitaxel. The compounds were prepared through a regioselective deacylation, reacylation sequence of suitably protected paclitaxel. The heterocyclic substituted diterpenes were synthesized from paclitaxel in four steps in high overall yields. Evaluation of these analogues in a microtubule assembly assay and for their cytotoxicity against B16 melanoma cells illustrated that these compounds had diminished activity compared to paclitaxel.
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ACKNOWLEDGEMENTS: We gratefully acknowledge the financial support from the National Institutes of Health (CA55141 and CA55160). Support is also acknowledged from the Kansas Health Foundation for postdoctoral fellowships awarded to G.C.B. Harriman and S. M. Ali and a predoctoral fellowship awarded to M. Hepperle. We acknowledge the excellent technical assistance of Ms. Christine Houston and Ms. Jeanne Ellermeier.
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