2,2′-Dihydroxy-3,3′-dimethoxy-5,5′-dimethyl-6,6′-dibromo-1,1′-biphenyl: preparation,resolution, structure and biological activity

The preparation and resolution of the titled conformationally stable biphenyl 1 has been performed in high chemical yield starting from creosol 2. Enantiopure biphenyls (aR)-(+)-1 and (aS)-(?)-1 were obtained by the corresponding menthylcarbonate diastereomer and successive reduction. The absolute configuration and specific rotation were correlated by X-ray analysis of the crystal structure of diastereopure menthylcarbonate (aS,1R,1′R,2S,2′S,5R,5′R)-(+)-16. Preliminary biological evaluation of both racemic enantiomers of 1 has been carried out on melanoma cell lines and significant and selective anticancer activity has been observed for the enantiomer (aS)-(?)-1.