灯盏乙素苷元4’-N-取代氨甲基苯甲酸酯的合成与活性研究

目的合成具有较强神经细胞氧化损伤保护作用的灯盏乙素苷元4’-N-取代氨甲基苯甲酸酯衍生物。方法灯盏乙素苷元与N-取代氨甲基苯甲酸在偶联剂N,N’-二环己基碳酰亚胺(DCC)/二甲基吡啶(DMAP)的作用下缩合后者经过酰氯/甲醇体系脱保护基,获得目标化合物(6a～6c)。并对受试化合物进行了神经细胞氧化损伤保护活性研究。结果合成的化合物及中间体均经过1H-NMR,ESI-MS进行了结构表征,确证结构与目标产物一致,受试化合物均具有较好的抗氧化活性,其中化合物6c活性明显好于维生素E、灯盏乙素。结论 4’-N-取代氨甲基苯甲酸酯前药设计方法能用于灯盏乙素苷元结构修饰,所采用的合成方法具有较好的实用性,能用于灯盏乙素苷元4’-N-取代氨甲基苯甲酸酯的制备。

Study on Synthesis and Anti-Oxidant Activity of Scutellarin 4'-N-Substituted(aminomethyl)Benzoate

Objective To synthesize scutellarein 4′-N-substituted（aminomethyl） benzoate derivatives with stronger neuroprotective activity.Methods 6,7-diphenyl ketal protection scutellarein was coupled with N-substituted（aminomethyl） benzoic acid by using DCC/DMAP as coupling agent and then the diphenyl ketal protective group was removed by using acetic acid chloride/methanol system to obtain target compounds（6a-6c）.Results The structure characterization of synthesized compounds and intermediates was performed by the methods of 1H NMR,ESI-MS,showing the consistency in structure with the target products.The tested compounds had better anti-oxidative activity in vitro,in which,the activity of compound 6c was superior to VE and scutellarin.Conclusion The prodrug design method of scutellarin 4′-N-substituted（aminomethyl） benzoate can be used to the structure modification of scutellarin.The synthetic method that we used has preferable practicality,which can be used in preparation of scutellarin 4′-N-substituted（aminomethyl） benzoate.