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Synthesis and anticancer activity of fluorinated analogues of combretastatin A-4 |
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| Authors: | Nicholas J. Lawrence Lucy A. Hepworth Alan T. McGown John A. Hadfield |
| Affiliation: | a Department of Chemistry, Cardiff University, P.O. Box 912, Cardiff CF10 3TB, UK b Department of Chemistry, UMIST, P.O. Box 88, Sackville Street, Manchester M60 1QD, UK c Department of Chemistry, Centre for Molecular Drug Design, University of Salford, Manchester M5 4WT, UK d CRC Drug Development Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK |
| Abstract: | The synthesis of a series of fluorinated benzaldehydes and their use in the Wittig synthesis of fluoro-substituted stilbenes is described. 3,5-Difluoro-4-hydroxybenzaldehyde (6) and 3-fluoro-4-methoxybenzaldehyde (11) are prepared by Duff formylation of 3,5-difluorophenol and 2-fluoroanisole, respectively. 2-Methoxy-3,4-difluorobenzaldehyde was obtained by Friedel-Crafts formylation of 2,3-difluoroanisole with α,α-dichloromethyl methyl ether. The aldehydes were used to make a series of fluorinated analogues of the anticancer combretastatins A-1, A-2 and A-4. The in vitro anticancer properties of the fluoro combretastatins are reported. The most active fluoro analogue 3-deoxy-3-fluoro-combretastatin A-4 (Z-2) retains the potent cell growth inhibitory properties of CA-4. |
| Keywords: | Combretastatin A-4 Combretum caffrum Stilbenes Wittig Benzaldehydes |
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