Asymmetric Synthesis of Antimitotic Combretadioxolane with Potent Antitumor Activity Against Multi-Drug Resistant Cells.

Abstract The (S,S)-enantiomer of combretadioxolane (3), designed as a chirally preorganized derivative of combretastatin A-4, exhibited quite strong tubulin polymerization-inhibitory activity (IC50: 4–6 μM). (S,S)- 3 is 20 times more potent than vincristine as an in vitro growth inhibitor (in terms of GI50) of the multi-drug-resistant (MDR) cell line PC-12, which produces P-glycoprotein.