Synthesis and Study of 4,4' Dihydroxy Biphenyl Derivatives with Potential Biological Activity

Hydroxylated biphenyls with a C2-symmetry axis have attracted considerable interest because of the biological activity exerted by a number of natural occurring compounds containing this moiety and because of their ability to transmit conformational information in stoichiometric and catalytic processes1. The geometrical possibilities offered by chemical transformation of the biphenyl skeleton make it a versatile building block in drug synthesis and catalysis2,3. Our study is aimed to prepare new biphenol derivatives as potential bioactive agents starting from commercial 4,4'-biphenol 1, an exametabolite producted from cyanobacteria. We have prepared, starting from biphenol 1, some biphenyl-coumarins following two synthetic strategies: 1) by Pechmann condensation carried out in the present of a ?-ketoesters under acidic condition; 2) by introduction of a methylketone functionality in the biphenol structure and then base-mediated cyclization with dimethylcarbonate. Due to the remarkable biological effects of phenol and biphenol prenylated4, we were able to prepare in one step, by Heck reaction, C-prenylated biphenols starting from biphenol 1 regioselectively brominated at 3,3' positions. Beneficial influence of microwaves irradiation on yields has been observed. With the aim to improve water-solubility, one hydroxyl group of biphenol 1 has been substituted by an aminoacidic or 2-hydroxybenzenecarboxylic group or a sugar unit, respectively. Most of the compounds were prepared according to the guidelines of Sustainable Chemistry and their biological evaluation is being in progress in our laboratory.