Synthesis and biological evaluation of novel paclitaxel (Taxol) D-ring modified analogues

The semisynthesis and biological activity of paclitaxel (Taxol) analogues i n which the oxygen atom in ring D is substituted by a sulfur or a selenium atom is presented. These derivatives were synthesized and tested in order t o make more transparent the role of the oxetane ring in the biological acti vity of paclitaxel. The sulfur derivatives were found to be less active tha n paclitaxel in biological assays, while the selenium derivative could not be converted to its 4-acyl analogue. The results with the sulfur analogues suggest that the oxygen atom in the oxetane ring plays an important role in the mechanism by which paclitaxel exhibits its anticancer activity.