摘要
目的设计合成杨梅素衍生物并进行体外抗氧化活性筛选。方法以天然产物杨梅素及杨梅苷为起始原料,通过Mannich反应、多步保护和脱保护方法等对其C-3、C-5、C-7位羟基以及C-8位进行选择性结构修饰,合成了一系列杨梅素衍生物,采用抗总氧DPPH模型对其进行自由基清除试验。结果与结论合成了18个未见文献报道的新化合物,目标化合物的结构经核磁共振氢谱和碳谱、高分辨质谱确证。体外抗氧化活性试验结果显示,11个杨梅素衍生物具有比先导物杨梅素及杨梅苷更强的抗氧化能力。本研究发现在杨梅素C-8和C-7位修饰可以显著提高抗氧化能力,自由基清除IC50值范围为6.71~10.98μg·mL^(-1)。本研究初步明确了杨梅素抗氧化活性关键结构和主要修饰位点,为后续深入研究构效关系提供指导。
A series of myricetin derivatives were synthesized by selective structural modification of the C-8,C-3,C-5 and C-7 position of myricetin.Five myricetin derivatives(2a-2e)were prepared by Mannich reaction with paraformaldehyde and secondary cyclic amine.With myricitrin as a starting material,the protection of the hydroxyl groups and hydrolysis of the glycoside under the acidic conditions,then the alkylation at the C-3 position and debenzylation gave the desired products(compounds 5a-5i).Two carbamates,compounds 7a and 7b,were generated from the modification of myricetin at the C5-position in the presence of N,N-dimethylcarbamoyl chloride and N,N-diphenylcarbamoyl chloride,respectively.Two isopentenyl-modified derivatives 10a and 10b were prepared by the modification of myricetin through a three-step reaction at the C7-position hydroxyl group.These compounds were characterized by 1H-NMR,13C-NMR and HR-MS.Their radical scavenging properties were evaluated by DPPH model.The results of antioxidant activity in vitro showed that 11 compounds had stronger antioxygenic activities than myricetin and myricitrin.Aminomethylation of myricetin at the C8-position and C7-substituted derivatives exhibited pronounced radical scavenging potency with IC50 values ranging from 6.71μg·mL^(-1)to 10.98μg·mL^(-1)towards quenching DPPH radical,and these compounds were more potent radical scavengers than myricetin.
作者
李吉顺
吴红林
朱子豪
吴光旭
李天磊
潘卫东
吴松
LI Ji-shun;WU Hong-lin;ZHU Zi-hao;WU Guang-xu;LI Tian-lei;PAN Wei-dong;WU Song(School of Pharmaceutical Science,Guizhou University of Traditional Chinese,Guiyang 550025,China;State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medcial University,Guiyang 550014,China;State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100050,China)
出处
《中国药物化学杂志》
CAS
CSCD
2021年第6期409-418,共10页
Chinese Journal of Medicinal Chemistry
基金
贵州医科大学省部共建药用植物功效与利用国家重点实验室2019年开放课题项目(FAMP201903K)
贵州省科技基金项目(黔科合平台人才[2017]5101)
国家自然科学基金项目(81703364)
贵阳中医学院研究生工作站创新资助项目(GNYL[2017]008号-7-Y)。
关键词
黄酮醇
杨梅素衍生物
天然结构修饰
抗氧化
favoniod
myricetin derivative
structural modification
antioxygenic activity
