含苯丙氨酸和1H-茚-1-酮类氯虫苯甲酰胺类似物的合成及杀虫活性  

Synthesis and insecticidal activity of chlorantraniliprole analogs containing phenylalanine and 1H-inden-1-one

作　　者：方佳琪 郝树林 杜晓华 FANG Jiaqi;HAO Shulin;DU Xiaohua(Catalytic Hydrogenation Research Center,Zhejiang University of Technology,Zhejiang Key Laboratory of Green Pesticides and Cleaner Production Technology,Zhejiang Green Pesticide Collaborative Innovation Center,Hangzhou 310014,China)

机构地区：[1]浙江工业大学催化加氢中心,浙江省绿色农药清洁生产技术研究重点实验室,浙江省绿色农药协同创新中心,杭州310014

出　　处：《农药学学报》2022年第4期713-722,共10页Chinese Journal of Pesticide Science

基　　金：国家重点研发计划(2016YFD0300708).

摘　　要：为了开发新的杀虫化合物,以氯虫苯甲酰胺为先导,2-甲基-3-氨基苯甲酸为起始原料,经过卤化生成5-氯-3-甲基-2-氨基苯甲酸;再与3-溴-1-(3-氯吡啶-2-吡啶基)-1H-吡唑-5-甲酸进行缩合反应,生成6-氯-2-(3-溴-1-(3-氯吡啶-2-吡啶基)-1H-吡唑-5-基)-8-甲基-4H-3,1-苯并噁嗪-4-酮;最后引入苯丙氨酸片段并经环化反应,分别合成了两个系列共计23个新化合物(4和5),其中化合物4为含苯丙氨酸的氯虫苯甲酰胺类似物,化合物5为由化合物4环化生成的含1 H-茚-1-酮片段的氯虫苯甲酰胺类似物,所有化合物的结构均通过核磁共振氢谱(1H NMR)、碳谱(13C NMR)和高分辨质谱(HRMS)的表征及确证。初步室内杀虫活性测试结果表明,多数目标化合物对黏虫Mythinma separata具有较高的杀虫活性,其中14个化合物在100 mg/L下对黏虫Mythinma separata的致死率为100%,化合物5k(1H-茚-1-酮片段中取代基为羟基)在4和0.8 mg/L下的致死率分别为90%和70%,其LC50值为0.55 mg/L。分子对接结果表明,化合物5k与氯虫苯甲酰胺一样,也是作用于鱼尼汀受体(RyR),但与靶标结合的氨基酸残基不同,这种差异可能对黏虫的抗药性治理研究有益。In order to develop new insecticidal compounds with chlorantraniliprole as the lead,2-methyl-3-aminobenzoic acid was used as the starting material,which was halogenated to generate 5-chloro-3-methyl-2-aminobenzoic acid;and then it was condensed with 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid to give 2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-chloro-8-methyl-4H-benzo[d][1,3]oxazin-4-one;finally,a phenylalanine fragment was introduced and cyclized to synthesize two series of 23 new compounds(4 and 5),compound 4 was chlorantraniliprole analog containing phenylalanine,and compound 5 was chlorantraniliprole analog containing 1H-inden-1-one fragment cyclized by compound 4.The structures of all compounds were characterized and confirmed by proton nuclear magnetic resonance spectroscopy(1H NMR),carbon spectroscopy(13C NMR)and high resolution mass spectrometry(HRMS).The preliminary indoor insecticidal activity tests showed that most target compounds had high insecticidal activity against oriental armyworm,Mythinma separata,with 14 compounds had 100%mortalities against M.separata at 100 mg/L,and compound 5k(the substituent in the 1H-inden-1-one fragment was hydroxyl)had 90%and 70%mortalities at 4 mg/L and 0.8 mg/L,respectively.And its LC50 value was 0.55 mg/L.In addition,molecular docking results showed that compound 5k also acted on ryanodine(RyR),just like chlorantraniliprole,but the amino acid residues bound to the target were different,which might be beneficial for research on drug resistance management of oriental armyworm.

关 键 词：1H-茚-1-酮 氯虫苯甲酰胺 苯丙氨酸 黏虫 杀虫活性 

分 类 号：O626.2[理学—有机化学] TQ455.4[理学—化学]