摘要
目的:通过在红景天苷及类似物的苯环上引入乙酰基,合成新型红景天苷类似物,以期获得神经保护活性更好的化合物。方法:以4-甲氧基苯乙醇对芳环进行傅克乙酰化反应,得到关键中间体3-乙酰基-4-羟基苯乙醇,再分别与糖基供体(四乙酰基溴代葡萄糖、四乙酰基氯代氨基葡萄糖)进行糖苷化反应,制备新型红景天苷类似物,并采用PC12细胞低糖低血清损伤模型来测定目标化合物对于低糖低血清损伤PC12细胞活力的影响。结果:合成的红景天苷类似物糖苷均经过质谱,核磁和元素分析的结构确证,红景天苷类似物预保护对低糖低血清损伤引起的PC12细胞活力的下降曾剂量依赖性地拮抗作用,尤其是化合物8a对低糖低血清损伤的拮抗作用显著高于红景天苷组。结论:所合成含有乙酰基的红景天苷类似物具有较好的对PC12细胞低糖低血清损伤的神经保护作用,将为今后进一步研究红景天苷类似物用于治疗神经退行性疾病打下坚实的基础。
Objective： In an attempt to improve its neuroprotective effects,novel salidroside analogues was synthesized by coupling the benzene ring of salidroside with acetyl group.Method： 4-Methoxyl phenethanol was treated with acetyl chloride and AlCl3 to form key intermediate 3-acetyl-4-methoxyl phenethanol by Friedel-Crafts acetylation reaction,the target compounds were prepared by glycosylation reaction of the key intermediate and tetraacetyl glucosyl bromide or tetraacetyl glucosamine chloride,and their neuroprotective activities have been evaluated against the hypoglycemia and serum limitation-induced cell death in differentiated PC12 cells.Results： Novel salidroside analogues were synthesized and their structures were confirmed by MS,1H NMR,and elemental analysis.Target compounds displayed protective effects on the cell viability,especially for compound 8a,which had a great potency superior to salidroside.Conclusion： The synthesized salidroside analogues containing acetyl group exhibited strong neuroprotective activities against the hypoglycemia and serum limitation-induced cell death in differentiated PC12 cells,which may provide potentially important information for further development of salidroside analogues and lay the basis for further studies on the neurodegenerative diseases for human clinical treatment.
出处
《交通医学》
2013年第3期213-216,220,共5页
Medical Journal of Communications
基金
国家自然科学基金资助项目(21242005
81171457)
南通市社会发展计划(AS2011016)
南通大学自然科学基金资助项目(11Z011)
