Novel C2-C3' N-peptide linked macrocyclic taxoids. Part 1: Synthesis and biological activities of docetaxel analogues with a peptide side chain at C3'.

A series of novel docetaxel analogues possessing a peptide side chain at the C3'-N position was synthesized. These compounds were designed to mimic a region of the alpha-tubulin loop that is equivalent to the paclitaxel binding pocket in beta-tubulin. Eight new peptidic taxoids were obtained and evaluated as inhibitors of microtubule disassembly, as well as for their cytotoxicity.