SYNTHESIS OF SCHIZANDRIN C ANALOGS Ⅱ.SYNTHESIS OF DIMETHYL-4,4′-DIMETHOXY-5,6,5′, 6′-DIMETHYLENEDIOXYBIPHENYL-2,2′-DICARBOXYLATE AND ITS ISOMERS

Dimethyl 4,4′-dimethoxy-5,6, 5′, 6′-dimethylenedioxybiphenyl-2,2′-dicarboxylate (Ⅴ_a) was an important intermediate used for the synthesis of schizandrin C analogs.Ⅴ_a was synthesized from gallic acid by esterification, monomethylation, formation of the methylenedioxy derivative, bromination and the Ullmann reaction successively.By using the mixed bromo compounds, separated from the mother liquid, as starting material for Ullmann reaction we obtained the isomer dimethyl 6,6°-dimethoxy-4,5,4′, 5′-dimethylenedioxybiphenyl-2, 2′-dicarb0xylate (Ⅴ_b) by repeated crystallization. In addition, the third isomer dimethyl 6,4′-dimethoxy,4,5,5′, 6′-dimethylenedioxybiphenyl-2,2′-diearboxylate (Ⅴ_c) was separated by column chromatography on silica gel. Ⅴ_a exhibits two crystalline forms with m. p. 158～160℃ and 179～181℃, both of them are effective in lowering the elevated SGPT level.Structures of the three isomers were further confirmed by NMR spectra and NOE effects. The differences between, these isomers in UV and IR Spectra were also observed.