五味子丙素类似物合成的研究—— Ⅱ.4,4′-二甲氧基-5,6,5′,6′-二次甲二氧基-2,2′-二甲氧羰基联苯及其异构体的合成

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

摘要: 在合成五味子丙素及共类似物的过程中,合成一些联苯中间体。其中4,4′-二甲氧基-5,6,5′,6′-二次甲二氧基-,2′-二甲氧羰基联苯经药理筛选具有降高血清谷丙转氨酶效果。本文报道上述联苯及其异构体的合成分离和有关光谱数据。

Abstract: 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.