PTP1B抑制剂4,5-二-(2-溴-4,5-二羟基苯甲基)-1,2-二苯酚的合成及生物活性

Synthesis and PTP1B inhhibitory activity investigation of 4,5-bis(2-bromo-4,5-dihydroxy-benzyl)-1,2-benzenediol

摘要:

以藜芦醛Ⅰ为起始原料，经过溴代、还原、傅克烷基化、脱甲基四步反应，合成了化合物4,5-二-(2-溴-4,5-二羟基苯甲基)-1,2-二苯酚 Ⅵ , 总收率为53.5%。采用1H-NMR, 13C-NMR, HREIMS等进行了结构表征。通过比色法对化合物 Ⅵ 及中间产物4,5-二-(2-溴-4,5-二甲氧基苯甲基)-1,2-二甲氧基苯 Ⅴ 进行蛋白酪氨酸磷酸酶1B(protein tyrosine phosphatase 1B ,PTP1B)抑制活性测定，结果显示化合物质量浓度为20 mg•L-1时，化合物 Ⅴ 和 化合物 Ⅵ 的PTP1B酶抑制率分别为25.08%和79.48%，表明化合物 Ⅵ 具有较好的PTP1B酶抑制活性。

Abstract:

4,5-bis(2-bromo-4,5-dihydroxy-benzyl)-1,2-benzenediol Ⅵ was synthesized from veratraldehyde Ⅰ, by employing bromination, reduction, Friedel-Crafts alkylation and demethylation with an overall yield of 53.5%. The structure of compound Ⅵ was elucidated by spectrum techniques including 1H-NMR,13C-NMR and HREIMS. Inhibitory activities of compound Ⅵ and 4,5-bis(2-Bromo-4,5-dimethoxy-benzyl)-1,2-dimethoxybenzene Ⅴ against protein tyrosine phosphatase 1B (PTP1B) were tested by colorimetric assay. Inhibition rates of compound Ⅴ and Ⅵ against PTP1B were 25.08% and 79.48% at 20 mg•L-1, respectively, which indicated that compound Ⅵ was an potential therapeutic agent for treatment of type 2 diabetes mellitus.