Synthesis and biological activity of 3′-alkyl- and 3′-alkenyl-3′-dephenyldocetaxels

Abstract

3-Alkyl- and 3′-alkenyl-3′-dephenyldocetaxels are synthesized from 10-deacetylbaccatin III based on the β-lactam synthon method in good yields. The cytotoxicity of the new taxoids are evaluated against different human tumor cell lines and their ability to inhibit the microtubules disassembly examined. The 3′-isobutenyl, 3′-crotyl, and 3′-isobutyl analogs possess very strong cytotoxicity as well as antitumor activity in vivo. 3′-Isobutenyl- as well as 3′-crotyl-3′-dephenyl-10-acetyldocetaxel shows ca. 20 times stronger activity against an adriamycin-resistant human breast cancer cell line (MCF7-R) than those o docetaxel and paclitaxel.