新型环己二酮类抑制剂的设计、合成及其生物活性研究  

Design,Synthesis and Bioactivity of New Cyclohexanedione Inhibitors

作　　者：李克建 吴双志[1] 王囡囡 朱晓磊 杨光富[1] 

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]四川警察学院治安系,泸州646000

出　　处：《有机化学》2017年第11期2978-2984,共7页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.21772057;21472065);高等学校学科创新引智计划(No.B17019);中央高校基本科研业务费(No.CCNU15A02013)~~

摘　　要：乙酰辅酶A羧化酶(Acetyl-Co A carboxylase,ACCase,EC 6.4.1.2)是一类重要的除草剂靶标,但是靶向ACCase的抗性杂草物种数目已跃居第三位,因此设计新型ACCase抑制剂显得尤为必要.本工作基于晶体结构数据,提出将芳氧苯氧丙酸酯类(APP)-活性腔和环己二酮类(CHD)-活性腔进行合理扩大,设计并合成了13个新型环已二酮类抑制剂.所有化合物均已通过核磁共振氢谱(~1H NMR)、碳谱(^(13)C NMR)和高分辨质谱(HRMS)确证.分子对接结果显示,2-([4-(2,4-二氯苯氧基)苯氧基]甲基)-5-[2-(乙硫基)丙基]环己烷-1,3-二酮(10a)可以同时占据APP和CHD活性腔.室内除草活性显示,部分化合物表现出了一定的除草活性,同时5-[2-(乙硫基)丙基]-2-[(4-苯氧基苯氧基)甲基]环己-1,3-二酮(10b)的除草谱较广,不仅可以防除禾本科杂草,还可以用来防除阔叶杂草.Acetyl-Co A carboxylase（ACCase,EC 6.4.1.2）was one of important herbicidal targets.However,the number of resistant weeds targeting to ACCase had risen to the third place among all of herbicidal targets.Therefore,it is of great importance to design new ACCase inhibitors.Herein,based on the crystal structures,aryloxyphenoxypropanotes（APP）-site and cyclohexanedioneoximes（CHD）-site were used to constructing APP＋CHD-site,and then thirteen compounds were designed and synthesized.All the newly prepared compounds were characterized by ~1H NMR,^（13）C NMR and HRMS.The molecular docking showed that 2-（（4-（2,4-dichlorophenoxy）phenoxy）methyl）-5-（2-（ethylthio）propyl）cyclohexane-1,3-dione（10a）could occupy not only APP-site,but also CHD-site.In addition,based on the herbicidal activity,some compounds showed some inhibition rate upon tested weeds.Most importantly,5-（2-（ethylthio）propyl）-2-（（4-phenoxyphenoxy）methyl）cyclohexane-1,3-dione（10b）showed a wide range of herbicidal spectrum,which could be used to inhibit not only poaceae weeds,but also broadleaf weeds.All these results indicated that this type of compounds worth of the further investigation.

关 键 词：乙酰辅酶A羧化酶 分子对接 有机合成 除草活性 

分 类 号：TQ457.2[化学工程—农药化工]