N-苯基氨基嘧啶甲酸-氨基酸衍生物的合成、杀菌活性及韧皮部传导性  

The synthesis,antifungal activity and phloem mobility of Nphenylaminopyrimidine acid and amino acid derivatives

作　　者：邓小倩 田尧 时锦超 朱宝玉 余林花 朱祥[1,2] 李俊凯 DENG Xiaoqian;TIAN Yao;SHI Jinchao;ZHU Baoyu;YU Linhua;ZHU Xiang;LI Junkai(College of Agriculture,Yangtze University,Jingzhou 434023,Hubei Province,China;Research and Development Center for Fine Chemicals,Guizhou University,Guiyang 550025,China)

机构地区：[1]长江大学农学院,湖北荆州434023 [2]贵州大学精细化工研究开发中心,贵阳550025

出　　处：《农药学学报》2025年第2期294-302,293,共10页Chinese Journal of Pesticide Science

基　　金：国家自然科学基金(No.32302417);教育部湿地生态与农业利用工程研究中心开放基金(No.KF202310);湖北省自然科学基金(No.2023AFB287);中国博士后科学基金(No.2022M710917).

摘　　要：为寻找具有韧皮部传导性的新型杀菌剂,本文设计、合成了一系列N-苯基氨基嘧啶甲酸-氨基酸衍生物,所有目标化合物的结构均通过核磁共振氢谱(^(1)H NMR)、碳谱(^(13)C NMR)及高分辨质谱(HRMS)进行表征,测定了所有目标化合物的离体杀菌活性和其在蓖麻幼苗韧皮部的传导性。杀菌活性测定结果表明:在50μg/mL下,大部分目标化合物对番茄灰霉病菌(Bortrytiscinerea)、柑橘炭疽病菌(Colletotrichumgloeosporioides)、油菜菌核病菌(Sclerotiniasclero-tiorum)、玉米小斑病菌(Bipolaris maydis)及烟草黑胫病菌(Phytophthora parasitica)均表现出一定的抑菌活性。化合物6b(L)、6c(L)和6d(L)对番茄灰霉病菌的抑制率均高于60%,与商品药剂嘧霉胺(60.78%)相当。其中,化合物6b(L)对番茄灰霉病菌的EC_(50)值为19.96μg/mL,优于嘧霉胺(38.82μg/mL)。此外,化合物5a、6b(D)、5d(D)、5e(L)、5j(L)对油菜菌核病菌抑制率均在80%以上。韧皮部传导性试验结果表明:对嘧霉胺进行氨基酸化修饰能赋予目标化合物韧皮部传导性,其中2-(N-苯基)氨基-6-甲基嘧啶-4-甲酸-D-丙氨酸表现出最好的韧皮部传导性,当孵育液中2-(N-苯基)氨基-6-甲基嘧啶-4-甲酸-D-丙氨酸质量浓度为50μg/mL时,2~4 h蓖麻韧皮部渗出液中目标化合物检出质量浓度为22.28μg/mL。同时发现,N-苯基氨基嘧啶甲酸-L-氨基酸衍生物在蓖麻幼苗体内容易被水解,释放出前体N-苯基氨基嘧啶甲酸,而N-苯基氨基嘧啶甲酸-D-氨基酸衍生物不存在水解现象。本研究成功获得了兼具较好杀菌活性与韧皮部传导性的新型杀菌剂候选化合物,可为新型韧皮部传导性杀菌剂的开发提供依据。To develop new fungicides with phloem mobility,a series of N-phenylaminopyrimidine acid and amino acid derivatives were designed and synthesized.All target compounds were characterized by ^(1)H NMR,^(13)C NMR and HRMS.The antifungal activities of all target compounds were tested in vitro and the phloem mobility were assayed in the castor bean seedling system.The results of the antifungal activity showed that most of the target compounds exhibited good antifungal activities against Bortrytis cinerea,Colletotrichum gloeosporioides,Sclerotinia sclerotiorum,Bipolaris maydis and Phytophthora parasitica at a concentration of 50μg/mL.In particular,6b(L),6c(L)and 6d(L)showed an inhibition rate of more than 60%against B.cinerea,which was equivalent to that of the commercial fungicide pyrimethanil(60.78%).Among them,compound 6b(L)showed the best antifungal activity,with an EC_(50) value of 19.96μg/mL,superior to pyrimethanil(38.82μg/mL).Furthermore,5a,6b(D),5d(D),5e(L)and 5j(L)showed excellent antifungal activities against S.sclerotiorum,with the inhibition rates of more than 80%.The results of the phloem mobility test showed that the amino acidification of pyrimethanil was effective in endowing the target compound with phloem mobility,among which methyl(6-methyl-2-(phenylamino)pyrimidine-4-carbonyl)-D-alanine showed the best phloem mobility.When the concentration of methyl(6-methyl-2-(phenylamino)pyrimidine-4-carbonyl)-D-alanine in incubation solution was 50μg/mL,the concentration was 22.28μg/mL in phloem sap after 2-4 h.Meanwhile,it was also found that N-phenylaminopyrimidine acid and L-amino acid derivatives were easily hydrolyzed to release the precursor N-phenylaminopyrimidine acid after being absorbed by castor bean cotyledons,but N-phenylaminopyrimidine acid and D-amino acid derivatives weren't hydrolyzed.In this study,some new fungicide candidates with both good antifungal activity and phloem mobility were successfully obtained,which can provide a basis for the development of new phloem mobility fungicides.

关 键 词：嘧霉胺 氨基酸 合成 抑菌活性 韧皮部传导性 

分 类 号：TQ455[化学工程—农药化工]