黄酮衍生物的合成及其抗炎活性研究

目的 设计合成一系列黄酮衍生物，并考察其抗炎活性。方法 采用Baker-Venkataraman反应合成单羟基取代的黄酮，进而经Williamson反应合成黄酮衍生物；以布洛芬为阳性对照药，采用巴豆油致小鼠耳肿胀实验对5个目标化合物（1a、1c、1d、2a、2c）的抗炎活性进行了评价。结果与结论 以2’,5’-二羟基苯乙酮或2’,4’-二羟基苯乙酮为原料，合成了12个未见文献报道的新化合物，其结构经核磁共振氢谱、高分辨质谱及红外光谱确证。初步的药理筛选结果表明化合物6-[2-(4-吗啉基)乙氧基]黄酮(1a)和2’-氟-7-(2-二甲氨基甲酰甲氧基)黄酮(2c)具有潜在的抗炎活性。

Study on synthesis and anti-inflammatory activity of flavone derivatives

Aim To synthesize a series of new flavone derivatives and to study their anti-inflammatory activity. Methods The mono-hydroxy substituted flavones were synthesized from 2’,5’-dihydroxy acetophenone and 2’,4’-dihydroxyacetophenone via Baker-Venkataraman reaction. The flavone derivatives were synthesized by reacting mono-hydroxy substituted flavones with some chloroacetamides or 2-chloroethylamines via Williamson reaction and the anti-inflammatory activity of five target compounds（1a、1c、1d、2a、2c） were evaluated by using the croton oil-induced ear edema test in Kunming mice with ibuprofen as positive control. Results and conclusion Twelve new flavone derivatives were synthesized and characterized by ¹H-NMR, HR-MS and IR. Preliminary pharmacological test showed that 6-[2-(4-morpholinyl)ethoxy]flavone (1a) and 2’-fluro-7-(2-dimethylamino-2-oxoethoxy)flavone (2c) possessed potent anti-inflammatory activity.