Synthesis and biological evaluation of 10,11-dihydrodictyostatin, a potent analogue of the marine anticancer agent dictyostatin.

By employing a diverted total synthesis strategy with late-stage intermediates, 10,11-dihydrodictyostatin ( 5) was prepared and evaluated in vitro for growth inhibition against a range of human cancer cell lines, including the NCI/ADR Taxol-resistant cell line. This novel dictyostatin analogue was found to retain potent antimitotic activity, with a comparable profile to discodermolide and Taxol, functioning by microtubule stabilization and G2/M arrest. These SAR studies provide further insight into the interaction between dictyostatin ( 1) and its tubulin target.