A solid-phase approach to DDB derivatives

Since the discovery of 2,2′-dimethoxycarbonyl-4,4-dimethoxy-5,6,5′,6′-biomethylenedioxy-biphenyl (DDB) as a potent anti-HBV agent, we have studied the structure-activity relationships of 4,4′-dimethoxy-5,6,5′,6′-dimethenedioxy-2-alkyloxycarbonyl-2′-(4-substituted benzyl piperazin-1-yl)carbonyl-biphenyl as anti-HBV agents. Therefore, it is rational to extend this study to the 3,3′-disustituted-4,4′-dimethoxy-5,6,5′,6′-dimethenedioxy-2-alkyloxycarbonyl-2′-Serine derivatives. Thus, in an attempt to develop an efficient method for the preparation of a large number of DDB derivatives, the reaction between a DDB acid chloride and serine derivatives on solid support was studied. The structure of resulted compounds was confirmed by LC-MS and 1H NMR analysis. Compounds 2a, 2d, 2f, 2j showed in vitro anti-HBV activity without significant toxicity up to 100 μM.