脱氧安息香与二氢异黄酮类化合物的合成及其对血管内皮细胞(VEC)损伤保护作用的初步活性研究

Synthesis and the cytoprotective activity in vascular endothelial cell of new deoxybenzoin and isoflavanone derivatives

目的设计合成系列新型脱氧安息香类和二氢异黄酮类化合物并初步测定其保护血管内皮细胞(VEC)活性。方法以间二甲苯为原料,经硝化、还原、水解、Hoeush-Houben缩合反应得到中间体脱氧安息香类化合物,该中间体经甲基保护,与多聚甲醛反应得到甲基保护的二氢异黄酮类化合物,再脱去甲基得到羟基二氢异黄酮类化合物。采用MTT法对目标化合物进行过氧化氢损伤VEC保护活性测定。结果与结论合成了12个新脱氧安息香类和12个新二氢异黄酮类化合物,目标化合物的结构经质谱、核磁共振氢谱确认。化合物3f、4c、4f、5c、5e对VEC有较好的保护作用。

As one kind of flavone family compounds,isoflavanones exhibit variable pharmacological activities depending on the nature of substituents present in the isoflavanone moiety.Deoxybenzoins are intermediates in the synthesis of isoflavones,and their structural similarities with isoflavanones lead to its biological activity studey in the same time.In this paper the structural modification of the target compounds was made mainly in the B ring to prepare isoflavanone and deoxybenzoin derivatives.Twelve new deoxybenzoins were synthesized by Hoeush-Houben condensation of phenylacetonitrile derivatives with substituted phloroglucinol which was prepared by successive nitration,reduction and hydrolysis of m-xylene,or followed by methyl-group protection,and twelve new isoflavanoes were obtained by the reaction of deoxybenzoins with para formaldehyde in the presence of diethylamine or by deprotection.Their structures were confirmed by1H-NMR and ESI-MS.The cytoprotective activity was investigated in VEC by MTT.The study showed that the compounds 3f,4c,4f,5c and 5e exhibited moderate cytoprotective activities,with protective rates varied from 11.48% to 38.69%.The results revealed that the compounds with a moderate electron-withdraw-ing substituent in the para position of the B ring,or an electron-donating group in the ortho or meta position of the B ring possessed potent activity,and the hydroxyl group in the A ring of isoflavanones may not be essential group for the activity.