1287199-75-0Relevant academic research and scientific papers
New para-para stilbenophanes: Synthesis by mcmurry coupling, conformational analysis and inhibition of tubulin polymerisation
Alvarez, Raquel,Lopez, Vilmari,Mateo, Carmen,Medarde, Manuel,Pelaez, Rafael
, p. 3406 - 3419 (2011/05/02)
The synthesis of a new family of methoxy-substituted [2.7]- and [2.8]paracyclophanes linked by 3-oxapentamethylene-1,5-dioxy and hexamethylene-1,6-dioxy bridges has been carried out by using the McMurry methodology. Related indole compounds were also synthesised. Olefin-to-diol ratios depended on the bridge length, the structure of the aromatic ring and the reaction conditions. Macrocyclisation, the methoxy substituents and the presence of a rigid indole moiety restricted the conformational equilibria, as observed by NMR spectroscopy and according to theoretical calculations. The synthesised compounds display micromolar tubulin polymerisation inhibitory activity. The conformational implications on the tubulin polymerisation inhibitory activity derived from the macrocyclisation when compared with combretastatins, closely related stilbenes, are also discussed. Flip-flop: McMurry coupling of dialdehydes was successfully used to complete the synthesis of macrocyclic stilbene analogues of combretastatins in variable yields (an example of which is depicted). These molecules have several exchanging conformations, as studied by NMR spectroscopy and theoretical calculations, and are the first macrocyclic inhibitors of tubulin polymerisation of their class. Copyright
