含1,2,3,4-四氢异喹啉片段磺酰肼和酰肼类化合物的设计、合成及生物活性研究  

Design,Synthesis and Bioactivity of Sulfonyl Hydrazides and Hydrazides Containing Fragment 1,2,3,4-Tetrahydroisoquinoline

作　　者：徐欢 吴鸿飞 张晓鸣 路星星 孙腾达 亓悦 林誉凡 杨新玲[1] 张莉[1] 凌云[1] Xu Huan;Wu Hongfei;Zhang Xiaoming;Lu Xingxing;Sun Tengda;Qi Yue;Lin Yufan;Yang Xinling;Zhang Li;Ling Yun(Department of Applied Chemistry,College of Science,China Agricultural University,Beijing 100193)

机构地区：[1]中国农业大学理学院应用化学系,北京100193

出　　处：《有机化学》2023年第2期725-733,共9页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.22077137,21472236)资助项目。

摘　　要：为了发现以漆酶作为潜在靶标的农用杀菌剂候选化合物,以天然产物四氢喹啉衍生物4-甲基-N’-(1,2,3,4-四氢喹啉-1-硫代羰基)苯磺酰肼(4bg)为先导,引入活性片段1,2,3,4-四氢异喹啉,设计合成了14个未见文献报道的磺酰肼类和9个酰肼类化合物.目标物结构均经过^(1)H NMR、^(13)C NMR、HRMS确证.离体抑菌活性测试结果表明,2-甲基-N’-(1,2,3,4-四氢异喹啉-2-碳硫酰基)苯磺酰肼(4b)对苹果腐烂病菌(V.mali)和油菜菌核病菌(S.sclerotiorum)均表现出显著的抑菌活性,EC_(50)分别为4.81,1.57μg/mL,优于先导化合物4bg.同时,5-甲基-N’-(1,2,3,4-四氢异喹啉-2-碳硫酰基)吡嗪-2-甲酰肼(5i)对苹果腐烂病菌、油菜菌核病菌、番茄灰霉病菌(B.cinerea)、稻瘟病菌(M.oryzae)、小麦赤霉病菌(F.graminearum)均表现较好的抑菌活性(EC_(50)=12.88~28.65μg/mL).此外,在50μg/m L浓度下,化合物4b和5i表现出一定的漆酶抑制活性(37.07%,35.49%),与阳性对照半胱氨酸(43.10%)相当.通过分子对接的方法分析了化合物4b和5i与漆酶蛋白的结合模式,为化合物进一步改造提供参考.In order to find agricultural fungicide candidates with lassase as potential target,14 unreported sulfonyl hydrazide and 9 hydrazide derivatives were designed and synthesized by replacing tetrahydroquinoline skeleton of the lead compound 4-methyl-N'-(1,2,3,4-tetrahydroquinoline-1-carbonothioyl)benzenesulfonohydrazide(4bg)with active fragment 1,2,3,4-tetrahydro-isoquinoline.The structures of the target compounds were confirmed by ^(1)H NMR,^(13)C NMR and HRMS.The in vitro bioassay showed that 2-methyl-N'-(1,2,3,4-tetrahydroisoquinoline-2-carbonothioyl)benzenesulfonohydrazide(4b)showed excellent fungicidal activity against V.Mali and S.sclerotiorum with EC_(50) values of 4.81 and 1.57μg/mL,respectively,which were better than that of lead compound 4bg.In addition,5-methyl-N'-(1,2,3,4-tetrahydroisoquinoline-2-carbonothioyl)pyrazine-2-carbohydrazide(5i)showed good broad-spectrum fungicidal activity against V.Mali,S.sclerotiorum,B.cinerea,M.oryzae and F.graminearum with EC_(50) range of 12.88~28.65μg/mL.Moreover,compounds 4b and 5i exhibited moderate laccase inhibitory activity(37.07%,35.49%),which were similar to that of cysteine(43.10%)at 50μg/mL.Furthermore,the binding modes of compounds 4b and 5i with laccase protein were simulated by molecular docking method,which provided guidance for further modification of compounds.

关 键 词：漆酶抑制剂 1 2 3 4-四氢异喹啉 (磺)酰肼类 抑菌活性 分子对接 

分 类 号：TQ455.4[化学工程—农药化工]