Heteroaromatic Taxol Analogues: The Chemistry and Biological Activities of 3′-Furyl and 3′-Pyridyl Substituted Taxanes

Abstract

A series of novel heterocyclic taxol analogues has been synthesized utilizing 2-azetidinones derived from the ester enolate-imine cyclocondensation. 2-Azetidinones possessing stereochemistry complementary to that of taxol's phenylisoserine side chain were synthesized in fair to high enantiomeric purity utilizing the chiral glycolate derived from Oppolzer's chiral auxiliary and the appropriate N-trimethylsilylaldimines. These novel analogues were evaluated in the microtubule assembly assay as well as tested for cytotoxicity against B16 melanoma cells. The 2-furyl analoug e 29 proved to be more active than the parent, taxol.