Design, synthesis and cytotoxicity of novel 3′-N-alkoxycarbonyl docetaxel analogs

An interesting by-product 9a was identified with very potent cytotoxicity. The structure of 9a was carefully characterized by 1D and 2D NMR and further confirmed by means of synthesis. The preliminary SAR study demonstrated that analogs with (R)-configuration were slightly more potent than analogs with (S)-configuration, and α,α-gem-dimethyl analogs 16g-i exhibited more potent cytotoxicity.