目的 基于药用植物辽东楤木Aralia elata中的单体五环三萜皂苷类天然产物齐墩果酸-3-O-β-D-吡喃葡萄糖醛酸进行结构修饰,并对其结构修饰物进行体外心肌保护活性研究。方法 分别以苷元齐墩果酸和熊果酸为起始原料,通过苄基保护、糖苷化、苄基脱保护、酰胺化、苯甲酰基脱保护共5步反应制得目标化合物,利用H9c2细胞评价该类衍生物的心肌保护活性。结果 设计并合成10个辽东楤木单体化合物的结构衍生物F1~F10,均经波谱技术确证结构。药理结果表明,10个化合物对H9c2细胞呈现不同程度的心肌保护活性,其中化合物F3的心肌保护活性与先导物活性相当。结论 化合物F1~F10均为未见文献报道的新化合物,具有潜在的心肌保护活性,值得深入研究。

Objective To modify the structure of natural monomeric compound based on oleanolic acid-3-O-β-D-glucuronide from medicinal plant Aralia elata and to evaluate the myocardial protection activity of the derivatives. Methods Taking oleanolic acid or ursolic acid as material, the target compounds were prepared by five steps of reactions and evaluated for myocardial protection effects by H9c2 cells in vitro. Results Ten derivatives F1-F10 were synthesized. The structures of the target compounds were identified by spectrum. Pharmacological results showed that all of the compounds had the different levels potency of myocardial protection effects in cells. In particular, compounds F3 showed the significant myocardial protection activity compared to lead compound. Conclusion The new compounds F1-F10 which show the potential of biological activity in myocardial protection, have not been reported in any literature and deserved further research.

国家自然科学基金资助项目(81302656);北京市自然科学基金资助项目(7144225);药植所创新团队发展计划资助项目