Synthesis and antiproliferative activities of ottelione a analogues.

Through the syntheses of its C-1 desvinyl, C-7 methylene, C-7 exocyclic ethylidene, and various C-3 phenylmethyl analogues, the structure-activity relationship of antimitotic ottelione A (4) against tubulin and various cancer cells was established. The results indicated that compound 4 was a colchicine-competitive inhibitor and that the C-1 vinyl group is unnecessary for its potency, whereas the C-7 exocyclic double bond is essential, possibly because of its irreversible interaction with tubulin. Further optimization of the substituents on the phenylmethyl group at the C-3 position generated compound 10g with a 3'-fluoro-4'-methoxyphenylmethyl substituent, which was 6-38-fold more active against MCF-7, NCI-H460, and COLO205 cancer cells relative to 4. Results from in vitro tubulin polymerization assay confirmed the potency of compounds 4, 10g, and 11a.

Novel ambiphilic dichlorocarbenoid equivalent in alkene cyclopropanation and carbonyl olefination.

The Ti-Mg-dichloromethylene complexes derived from the oxidative addition of CCl4 to the Mg-TiCl4 bimetallic species serve as a novel class of ambiphilic dichlorocarbenoid equivalents. Not only is Ti-Mg-dichlorocarbenoid highly selective but also it seems highly reactive in both alkene cyclopropanations and carbonyl dichloromethylenations.