天然黄酮Mannich碱衍生物的合成及生物活性研究  

Synthesis and Bioactivity of Natural Flavones Mannich Base Derivatives

作　　者：刘重阳[1] 阮文山[1,2] 王盛淳 汪秋安[1] 

机构地区：[1]湖南大学化学化工学院,湖南长沙410082 [2]胡志明市工业大学化工系,越南胡志明999100

出　　处：《林产化学与工业》2016年第1期35-41,共7页Chemistry and Industry of Forest Products

基　　金："十二五"国家科技支撑计划资助(2012BAD31B02);国家自然科学基金资助项目(J1210040)

摘　　要：以柚皮苷和橙皮苷为原料,经碘/吡啶脱氢,O-甲基化和糖苷水解等反应,分别合成了2种天然黄酮芹菜素-5,4'-二甲醚(1)和木犀草素-5,3',4'-三甲醚(2)。然后以1和2为底物,分别与甲醛、二级胺在酸性醇溶剂中发生微波协助的Mannich反应,对黄酮8-位进行胺甲基化修饰,合成了15个新型黄酮Mannich碱衍生物3~17。所合成的化合物经~1H NMR、^(13) C NMR和MS等进行了结构确证,并采用细胞计数Kit-8(CCK-8)法测试了化合物1~17对子宫颈癌Hela细胞的体外抑制活性。结果表明,化合物1、2、7、9、10、12和17对Hela细胞增殖具有明显的抑制活性,其中化合物10、12和17的半数抑制浓度(IC_(50))分别为16.13、29.04和9.14μmol/L,活性高于阳性对照药物顺铂(IC_(50)为41.25μmol/L)。Two naturally occurring flavones,apigenin-5,4’-dimethy ether（ 1） and lutedin-5,3’,4’-trimethyl ether（ 2）,were synthesized through I2/ Py dehydrogenation,O-methylation and glycoside hydrolysis reaction,using naringin and hesperidin as raw materials. Based on Mannich reaction of flavones 1 or 2 with various secondary amines and formaldehyde in acidic alcohol solvent with microwave assisted,fifteen novel flavones Mannich base derivatives 1- 17 were synthesized. The structures of all synthesized compounds were confirmed by1 H NMR,13 C NMR and MS techniques. Furthermore,all compounds were tested for anti-proliferative activities on human cervical carcinoma Hela cells using cell counting Kit-8（ CCK-8）. The results showed that compounds 1,2,7,9,10,12 and 17 exhibited distinct anti-proliferative activities against Hela cells. Among them,compounds 10,12 and 17 displayed higher activities with inhibitory concentration 50%（ IC50） of 16.13,29.04 and 9.14 μmol/L than the positive control cis-platin（ IC50= 41. 25 μmol / L）.

关 键 词：黄酮类 Mannich碱衍生物 合成 生物活性 

分 类 号：TQ35[化学工程]