Topliss approach to the synthesis of biologically active substituted N-benzoyl taxol analogues

A series of compounds, directed by the Topliss Operational Scheme, were synthesized and evaluated to investigate structure activity relationships of the N-benzoyl moiety of taxol. Evaluation of the newly prepared derivatives in the microtubule assembly assay and for cytotoxicity revealed that they possessed biological properties similar to taxol. Nine novel substituted N-benzoyl analogues of taxol were prepared, using the Topliss approach to drug design. The taxanes were prepared from N-acyl-3-hydroxy-4-phenyl-2-azetidinones and baccatin III or by acylation of N-debenzoyltaxol. In vitro biological evaluation revealed that these analogues had activity similar to taxol.