Synthesis and conformational analysis of macrocyclic dihydroxystilbenes linked between the para-para positions.
A new family of diphenylethanes has been synthesized as conformationally restricted analogues of antimitotic combretastatins. The two phenyl rings are linked between the para-phenolic positions through a 3-oxapentamethylene or hexamethylene chain. The key macrocyclization step was achieved in moderate yields by using an intramolecular McMurry pinacol coupling of linked aromatic dialdehydes, except for the nitro-substituted compounds. The relative stereochemistry of the isomeric pinacols was determined by a combination of spectroscopic, chemical derivatization, and molecular-modeling approaches. The NMR spectra of these compounds (with a polyoxygenated crownophane skeleton) indicate severe conformational restrictions relative to their parent combretastatins; the rotation of the phenyl rings is hampered by interactions of their substituents and the linker and the conformational restrictions imposed by the substituted bridge.
Mateo
Carmen
C
Laboratorio de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
López
Vilmarí
V
Medarde
Manuel
M
Peláez
Rafael
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D001632:Bibenzyls; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001632:Bibenzyls; D013267:Stilbenes; C040105:combretastatin