Synthesis and biological evaluation of D-ring-modified taxanes: 5(20)-azadocetaxel analogs

Two 5(20)-aza analogs of docetaxel, N-20-benzyl-5(20)-azadocetaxel (5) and 5(20)-azadocetaxel (6), have been synthesized from 10-deacetylbaccatin III, The key steps of this synthesis involved the direct introduction of a C-5 leaving group while ring opening and the intramolecular nucleophilic attack of the C-20 amino group at C-5. Both compounds were inactive on the in vitro cytotoxic assay, and only the azadocetaxel 6 retains an antitubulin activity, but 16 times less than docetaxel.