含双酰胺结构的氟吡菌酰胺衍生物的设计、合成及生物活性研究  

Design,Synthesis and Bioactivity of Fluopyram Derivatives Containing Diamide Moiety

作　　者：许庆博 梁培博 路慧哲[1] 金淑惠[1] 董燕红[1] 张建军[1] Xu Qingbo;Liang Peibo;Lu Huizhe;Jin Shuhui;Dong Yanhong;Zhang Jianjun(College of Science,China Agricultural University,Beijing 100193)

机构地区：[1]中国农业大学理学院,北京100193

出　　处：《有机化学》2021年第8期3116-3125,共10页Chinese Journal of Organic Chemistry

基　　金：国家重点研发计划(No.2018YFD0200100);国家自然科学基金(No.21772230)资助项目.

摘　　要：基于活性亚结构拼接法,将双酰胺结构引入氟吡菌酰胺的骨架中,设计并合成了22个含双酰胺结构的氟吡菌酰胺衍生物.结构经过^(1)H NMR、^(13)C NMR 和 HRMS鉴定,目标化合物对4种植物病原真菌离体的抑制活性以及对秀丽隐杆线虫的离体杀虫活性也进行了研究.结果显示,在50 mg/L的浓度下,大部分化合物对苹果腐烂病原菌及油菜菌核病原菌有较高的抑制活性,抑制率在80%以上.其中N-(2-(3-氯-5-(三氟甲基)吡啶-2-基)乙基)-2-(3-氟苯甲酰胺基)苯甲酰胺(7f)对苹果腐烂病原菌的 EC_(50)为6.12 mg/L,高于对照药剂氟吡菌酰胺(35.5 mg/L);对苹果腐烂病原菌SDH酶抑制活性在100 μmol的浓度下达到90.1%;对秀丽隐杆线虫的致死率在200 mg/L浓度下为87%.分子对接结果表明,SDH可能是化合物的潜在靶标.According to the principle of combination of bioactive substructure,the structure of diamide was introduced into fluopyram,and 22 novel fluopyram derivatives containing diamide were designed and synthesized.The structures of the target compounds were characterized by ^(1)H NMR,^(13)C NMR and HRMS.The inhibitory activities of the target compounds against four plant pathogenic fungi and in vitro insecticidal activities against Caenorhabditis elegans were studied.The results showed that under the concentration of 50 mg/L,most of the compounds showed moderate fungicide activity against Cytospora sp.and Sclerotinia sclerotiorum with inhibition rate over 80%.The EC_(50) of N-(2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethyl)-2-(3-fluorobenzamido)benzamide(7f)to Cytospora sp.was 6.12 mg/L,which is higher than fluopyram(35.5 mg/L),the SDH essay showed that enzyme inhibition rate of 7f reached 90.1%,and the mortality rate against C.elegans was 87% at 200 mg/L.The results of molecular docking show that the SDH may be a potential target of the compounds.

关 键 词：琥珀酸脱氢酶 杀线虫剂 双酰胺 氟吡菌酰胺 

分 类 号：TQ450.1[化学工程—农药化工]