花旗松素衍生物的设计、合成及抗炎活性构效关系研究

Design,Synthesis and Structure-Activity Relationship of Taxifolin Derivatives as Anti-inflammatory Agents

以邻羟基苯乙酮衍生物和苯甲醛衍生物为原料,经缩合、氧化、水解生成A环和/或B环取代的花旗松素衍生物4a^4o。以邻氨基苯乙酮衍生物和苯甲醛衍生物为原料,经同样的方法得到C环改变的花旗松素衍生物4p^4r。共设计合成19个化合物,其结构经核磁共振氢谱、碳谱分析确证。测定所合成化合物对小鼠巨噬细胞RAW264. 7的体外抗炎活性。结果表明:A环上的5,7位酚羟基是其发挥活性的关键性基团; B环4/位的卤素取代基对于活性影响极大,特别是氟原子的取代效果尤其显著;改变C环的结构都会使其炎症因子的抑制作用降低。

The 2'-hydroxyl chalcone derivatives 3a～3o were prepared by condensation of 2′-hydroxyhypnone derivatives and phenyl aldehyde derivatives under alkali.After oxidation and hydrolysis,A and/or B-ring substitut-ed taxifolins 4a-4o were obtained.Then C-ring varied taxifolins 4p～4r were synthesized by oxidative hy-drolysis of 2′-azyl chalcone derivatives 3p-3r,which were prepared by method above.19 compounds were synthesized and their structures were confirmed by 1H NMR and 13 C NMR.To best of our knowledge,13 of them were unknown in the literature.The anti-inflammatory activity of synthesized compounds was evaluated against RAW264.7 cell in vitro.The preliminary results indicated that 4,4c,4i,4l and 4m showed good anti-inflammatory activity(P<0.001).Structure-activity relationship showed that the 5,7-dihydroxyl substitution located in the A-ring was critical for anti-inflammatory activity.The 4/-fluorine substitution located in the B-ring has excellent influence.The anti-inflammatory activity reduced or disappeared when C-ring was varied.