HETEROAROMATIC TAXOL ANALOGS - THE CHEMISTRY AND BIOLOGICAL-ACTIVITIES OF 3'-FURYL AND 3'-PYRIDYL SUBSTITUTED TAXANES

A series of novel heterocyclic taxol analogues has been synthesized ut ilizing 2-azetidinones derived from the ester enolate-imine cycloconde nsation. 2-Azetidinones possessing stereochemistry complementary to th at of taxol's phenylisoserine side chain were synthesized in fair to h igh enantiomeric purity utilizing the chiral glycolate derived from Op polzer's chiral auxiliary and the appropriate N-trimethylsilylaldimine s. These novel analogues were evaluated in the microtubule assembly as say as well as tested for cytotoxicity against B16 melanoma cells. The 2-furyl analogue 29 proved to be more active than the parent, taxol.