SYNTHESIS AND BIOLOGICAL-ACTIVITY OF 3'-ALKYL-3'-DEPHENYLDOCETAXEL AND 3'-ALKENYL-3'-DEPHENYLDOCETAXEL

3'-Alkyl- and 3'-alkenyl-3'-dephenyldocetaxels are synthesized from 10 -deacetylbaccatin III based on the beta-lactam synthon method in good yields. The cytotoxicity of the new taxoids are evaluated against diff erent human tumor cell lines and their ability to inhibit the microtub ules disassembly examined. The 3'-isobutenyl, 3'-crotyl, and 3'-isobut yl analogs possess very strong cytotoxicity as well as antitumor activ ity in vivo. 3'-Isobutenyl- as well as 3'-crotyl-3'-dephenyl-10-acetyl docetaxel shows ca. 20 times stronger activity against an adriamycin-r esistant human breast cancer cell line (MCF7-R) than those of docetaxe l and paclitaxel.