咖啡酸酰胺类衍生物的合成及调脂活性研究

Synthesis and lipid-regulating evaluation of caffeic acid amide derivatives

目的设计并合成天然产物咖啡酸的酰胺类衍生物,并对该系列化合物进行体外抗脂质代谢紊乱活性评价。方法以咖啡酸为起始原料,卡特缩合剂(BOP)为缩合剂,与十四种胺依次反应制得目标产物,利用人肝癌HepG2细胞评价该类衍生物的调脂活性。结果设计并合成14个咖啡酸酰胺类化合物CA1～CA14,均经波谱技术确证结构。药理实验结果表明,14个化合物对HepG2细胞呈现不同程度的调血脂活性,其中衍生物CA6的调血脂活性优于先导物咖啡酸和阳性药辛伐他汀。结论化合物CA6、CA7和CA11均为未见文献报道的咖啡酸酰胺类新化合物,其中CA6和C11具有潜在的调脂生物活性,值得进一步深入研究。

Objective To evaluate the anti-lipid metabolic disorder activities of these compounds in vitro, the natural caffeic acid amide derivatives were designed and synthesized. Methods Using caffeic acid as start material, BOP as a condensing agent, and the target compounds were sequentially prepared with fourteen amines, and then the lipid-regulating effect was evaluated using HepG2 cells. Results Fourteen caffeic acid amide compounds CA1—CA14 were synthesized. The structures of the target compounds were identified by spectrum. Pharmacological results showed that fourteen derivatives have potency of lipid-regulating in different levels. In particular, compound CA6 showed significant lipid-regulating effects compared to the lead compounds caffeic acid and Simvastatin. Conclusion Compound CA6, CA7, and CA11 had not been reported in any literatures before. Among them, the novel compounds CA6 and CA11 have showed potential of lipid-regulating activities, and deserved further research.