| abstract |
Substituted diphenylethylenes such as the compound known as Combretastatin A4 (cis-1-(3-Hydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene) and analogues or derivatives thereof are synthesised in a convergent process wherein the ylide form of a triphenyl phosphonium salt of a trialkoxy benzyl halide is reacted in a Wittig coupling reaction with a benzaldehyde compound having a protected hydroxyl or O-phosphate group in the 3-position and an alkoxy group in the 4-position. Combretastatin A4 analogues and derivatives having improved or enhanced aqueous solubility and photostability characteristics are disclosed suitable for use as biodegradable pro-drugs in pharmaceutical formulations for clinical use. |