The semisynthesis and biological activity of paclitaxel (Taxol) analogues in which the oxygen atomin ring D is substituted by a sulfur or a selenium atom is presented. These derivatives weresynthesized and tested in order to make more transparent the role of the oxetane ring in thebiological activity of paclitaxel. The sulfur derivatives were found to be less active than paclitaxelin 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 animportant role in the mechanism by which paclitaxel exhibits its anticancer activity.