SYNTHESIS OF 2-O-HETEROAROYL TAXANES - EVALUATION OF MICROTUBULE ASSEMBLY PROMOTION AND CYTOTOXICITY

A series of heterocyclic taxanes were synthesized and evaluated to inv estigate structure activity relationships at the 2-position of paclita xel. The compounds were prepared through a regioselective deacylation, reacylation sequence of suitably protected paclitaxel. The heterocycl ic substituted diterpenes were synthesized from paclitaxel in four ste ps in high overall yields. Evaluation of these analogues in a microtub ule assembly assay and for their cytotoxicity against B16 melanoma cel ls illustrated that these compounds had diminished activity compared t o paclitaxel.