On the synthesis and biological properties of isocombretastatins: a case of ketone homologation during Wittig reaction attempts

Abstract

New isocombretastatins were synthesized by reacting the corresponding phenstatin analogs with CH₃PPh₃Br in presence of tBuOK. These new derivatives showed significant activities against cellular proliferation and tubulin polymerization. In particular, monomethoxylated derivatives of phenstatin and isoCA-4 exhibit similar activities to those of parent phenstatin. Attempts of the Wittig reaction on 2- (or 4-) methoxy-4′-nitrobenzophenones in the same conditions do not lead to the expected isocombretastatins but to methyleneketones with the exclusion of triphenylphosphine. A mechanism for this new ketone homologation was proposed.