一锅煮法由芦丁合成槲皮素五芳基甲酸酯及生物活性研究  

Synthesis and Bioactive Evaluation of Quercetin Pentabenzoates from Rutin in One-pot Procedure

作　　者：冯亚莉 李浩 白现祥 刘双强 裴媛媛 曹智威 廖国一 翟广玉 FENG Ya-li;LI Hao;BAI Xian-xiang;LIU Shuang-qiang;PEI Yuan-yuan;CAO Zhi-wei;LIAO Guo-yi;ZHAI Guang-yu(School of Pharmacy and Chemical Engineering,Zhengzhou University of Industrial Technology,Zhengzhou 451100,China)

机构地区：[1]郑州工业应用技术学院药学与化学工程学院,河南郑州451100

出　　处：《化学试剂》2021年第12期1638-1643,共6页Chemical Reagents

基　　金：郑州市高等学校名师技术技能工作室项目(郑教高[2015]70号);河南省高等学校重点科研项目(21B350003);河南省大学生创新创业训练计划项目(S202112747015)。

摘　　要：使用易得的芦丁和芳酰氯为原料,利用“一锅煮法”策略,在吡啶的促进下首次实现了槲皮素五芳基甲酸酯类化合物的高效制备。该策略避免了直接使用槲皮素作为原料容易发生氧化或聚合等副反应,且后处理仅需重结晶的简单操作,即可以44%~68%产率得到10个尚未见文献报道的新颖五芳基甲酸酯类化合物,目标产物的结构经核磁、质谱、红外确证。采用溴化噻唑蓝四氮唑(MTT)法,初步评价了目标化合物对人食管癌细胞EC-109、人食管鳞癌细胞EC-9706、人胃癌细胞SGC-7901及小鼠黑色素瘤细胞B16-F10等4株肿瘤细胞的体外增殖抑制作用。生物活性测试结果表明所合成的10个槲皮素五芳基甲酸酯类衍生物对这4种癌细胞均有不同程度的抑制作用,其中槲皮素五对氯苯甲酸酯对EC-9706的半数抑制浓度IC_(50)为(26.6±1.3)μmol/L,活性分别比母药槲皮素、槲皮素五乙酸酯和对照药5-氟尿嘧啶提高了1~3倍,是一个很有潜力的新型抗癌候选化合物。这也证明通过对槲皮素的五芳基酯衍生化策略是克服母体分子槲皮素的生物利用率低、并开发具有高效生物活性分子的一种有效手段。A highly efficient one-pot procedure for the preparation of quercetin pentabenzoates by the utilization of easily accessible rutin and aroyl chlorides in the presence of pyridine was developed.By overcoming the plausible oxidation or polymerization side reactions by direct employing quercetin as the starting material,ten unknown quercetin pentabenzoates were synthesized in 44%~68%yields after simple recrystallization.The structures of these newly synthesized molecules were identified by NMR,MS and IR spectra,respectively.In order to investigate the effects of inhibitory proliferation in vitro of the obtained ten target compounds on four types of cancer cells,including human esophageal carcinoma cell line EC-109,human esophageal squamous carcinoma cell line EC-9706,human gastric cancer cell line SGC-7901,and mouse melanoma cell line B16-F10,MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetraazolium bromide)assay were carried out and the results indicated that all 10 quercetin pentabenzoates showed different degrees of inhibitory effects on the four types of cancer cells.Among them,quercetin penta(4-chlorobenzoate)has been identified as a very promising anti-tumor candidate because of its better inhibition effect on EC-9706 growth with the half maximal inhibitory concentration(IC_(50))value of(26.6±1.3)μmol/L,higher one to three folds than that of the parent quercetin,quercetin pentacetate,and control medicine 5-fluoropyrimidine.The study demonstrated that the pentabenzoation of quercetin was a reliable strategy to develop new effective bioactive molecules by overcoming the low bioavailability of quercetin.

关 键 词：一锅煮法 槲皮素五芳基甲酸酯 酯化反应 合成 生物活性评价 

分 类 号：O629.9[理学—有机化学]