超声辅助合成新型二氢嘧啶-2(1H)-硫酮衍生物及其生物活性研究  

Ultrasound-assisted Synthesis and Biological Activities of Novel Dihydropyrimidine-2(1H)-thione Derivatives

作　　者：周伟 陈斯琴 刘进兵 ZHOU Wei;CHEN Si-qin;LIU Jin-bing(School of Food and Chemical Engineering,Shaoyang University,Shaoyang 422000,China)

机构地区：[1]邵阳学院食品与化学工程学院

出　　处：《合成化学》2019年第12期952-956,共5页Chinese Journal of Synthetic Chemistry

基　　金：湖南省教育厅重点项目(15A172);邵阳学院研究生科研创新项目(CX2018SY048)

摘　　要：以苯乙酮与取代苯甲醛(1a^1e)为起始原料,在碱性条件下制得中间体查尔酮(2a^2e);在超声辅助下,合成了一系列硫代嘧啶酮类化合物(3a^3e),其中3a、3d和3e为新化合物,其结构经1 H NMR,13 C NMR,IR和MS(ESI)表征。研究了3a^3e对酪氨酸酶和α-葡萄糖苷酶的抑制活性及抗氧化活性。结果表明:4-(2-甲氧基苯基)-6-苯基-3,4-二氢嘧啶-2(1 H)-硫酮(3b)抑制酪氨酸酶活性最好,IC 50为0.676 mmol·L-1,与阳性对照曲酸相当。以3b为例进行了抑制酪氨酸酶动力学与分子对接研究。结果表明:3b为竞争型抑制剂,苯环可能为其活性基团。Chalcones(2a^2e)were obtained from acetophenone and substitued benzaldehyde(1a^1e)under alkaline conditions.Then pyrimidine thione derivatives(3a^3e)were synthesized by ultrasound-assisted synthesis method from 2a^2e.Among them,3a,3d and 3e were novel compounds.The structures were characterized by 1 H NMR,13 C NMR,IR and MS(ESI).Inhibitory tyrosinase activities,inhibitory alpha-glucosidase activities and antioxidant activities of 3a^3e were investigated.The results showed that 4-(2-methoxyphenyl)-6-phenyl-3,4-dihydropyrimidine-2(1 H)-thione(3b)exhibited best inhibition on mushroom tyrosinase with IC 50 of 0.676 mmol·L-1.The inhibitory kinetics and molecular docking were studied using 3b as sample.Kinetic results showed that 3b was a competitive inhibitor.Molecular docking results indicated that benzene ring might be an active group.

关 键 词：超声辅助 嘧啶硫酮 合成 抗氧化活性 抑制酪氨酸酶活性 抑制α-葡萄糖苷酶活性 分子对接 

分 类 号：O626.415[理学—有机化学]