Topliss Approach to the Synthesis of Biologically Active Substituted N- Benzoyl Taxol Analogues.

Abstract 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.