title: New para-para stilbenophanes: synthesis by McMurry coupling, conformational analysis and inhibition of tubulin polymerisation.
abstract: 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.
authors.affiliation: Laboratorio de Química Orgánica y Farmacéutica, Facultad de Farmacia. Universidad de Salamanca, Campus Miguel de Unamuno, 37007, Salamanca, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Álvarez
authors.forename: Vilmarí
authors.initials: V
authors.lastname: López
authors.forename: Carmen
authors.initials: C
authors.lastname: Mateo
authors.forename: Manuel
authors.initials: M
authors.lastname: Medarde
authors.forename: Rafael
authors.initials: R
authors.lastname: Peláez
mesh_terms: D000075202:Contraindications; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D058105:Polymerization; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000737:chemistry*
chemical_list: D013267:Stilbenes; D050257:Tubulin Modulators; C504774:stilbenophane