SYNTHESIS AND BIOLOGICAL EVALUATION OF PACLITAXEL ANALOGS MODIFIED INRING-C

Both 7-deoxy-7 alpha-azidopaclitaxel (6) and 7-deoxy-Delta(6,7)-paclit axel (4) can be prepared from paclitaxel-7-0-triflate (2b). Oxidation of 7-deoxy-Delta(6,7)-paclitaxel with dioxirane yields the epoxide 7, while oxidation with osmium tetroxide yields 6 alpha-hydroxy-7-epipacl itaxel (9), and acylation of this gives the 6 alpha-acyloxy-7-epipacli taxel derivatives 11a-d. No compound was as effective at promoting tub ulin assembly as paclitaxel, but most stabilized polymer as well as or better than paclitaxel. Compounds 4, 6, 7, 9, and 11d differed little from paclitaxel in their cytotoxicity for human Burkitt lymphoma CA46 cells.