含腙结构单元的氨基嘧啶衍生物的合成与生物活性研究  

Synthesis and Biological Evaluation of Pyrimidine Derivatives Containing Hydrazine Structural Unit

作　　者：何海峰 夏芹 贺红武[1] He Haifeng;Xia Qin;He Hongwu(Key Laboratory of Pesticide and Chemical Biology of Ministry of Education,College of Chemistry,Central China Normal University,Wuhan 430079;School of Chemistry and Chemical Engineering,Jiangxi Science and Technology Normal University,Nanchang 330013)

机构地区：[1]华中师范大学化学学院农药与化学生物学教育部重点实验室,武汉430079 [2]江西科技师范大学化学化工学院,南昌330046

出　　处：《有机化学》2019年第8期2295-2302,共8页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.21877047,21867011);江西省教育科技厅基金(No.GJJ170672)资助项目~~

摘　　要：丙酮酸脱羧酶是连接糖酵解与三羧酸循环的关键酶,目前尚无以丙酮酸脱羧酶(PDHc-E1)为靶标的杀菌剂.拟通过设计针对微生物PDHc-E1的抑制剂来获得具有杀菌活性的化合物.以课题组前期发现的E.coli PDHc-E1抑制剂L为先导化合物进行结构修饰,通过肼与醛的缩合反应合成了14个新型含腙结构单元的氨基嘧啶衍生物I作为潜在的PDHc-E1抑制剂.发现2-甲基-4-氨基-5-(甲基-4-溴苯腙)-嘧啶(I-6)不仅对E.coli PDHc-E1显示较好的活性(IC50=26.45 μmol/L),同时对真菌花生褐斑(EC50 14.11μg/mL)和苹果轮纹(EC50 0.64 μg/mL)显示了高效活性,具有进一步研究的价值.由此,通过对先导结构2-甲基-4-氨基嘧啶衍生物L中的桥键进行结构修饰,获得了对E.coli PDHc-E1具有抑制作用的高效杀菌活性的化合物.Pyruvate dehydrogenase multienzyme complex (PDHc) is a key enzyme linking glycolysis and the tricarboxylic acid cycle.Currently,there is no fungicide targeting pyruvate decarboxylase (PDHc-E1),the purpose of this study was to obtain compounds with bactericidal activity by designing inhibitors against PDHc-E1.On the basis of lead compound L,fourteen novel aminopyrimidine derivatives I were designed and synthesized by the condensation reaction of hydrazine and aldehydes as potential PDHc-E1 inhibitors.The most effective 5-((2-(4-bromophenyl)hydrazono)methyl)-2-methylpyridin-4-amine (I-6) with good E.coli PDHc-E1 enzyme inhibitory activity (IC50=26.45 μmol/L) exhibited most powerful inhibitory potency against Cercospora arachidicola Hori (EC50 14.11 μg/mL) and Physalospora piricola Nose (EC50 0.64 μg/mL).Therefore it could obtain the compound with antifungal activity against microorganism PDHc-E1 enzyme by modifying the bridged linkage in lead structure 2-methyl-4-amino-pyrimidine derivatives L.

关 键 词：丙酮酸脱羧酶 杀菌剂 先导化合物 2-甲基-4-氨基嘧啶衍生物 

分 类 号：TQ455.4[化学工程—农药化工]