基于Strecker反应的含氰基多取代吡唑的合成及生物活性研究

doi:10.6023/cjoc201812019

摘要/Abstract

为探索多取代吡唑胺的Strecker反应及含氰基吡唑化合物的生物活性，首次实现了ZnI₂催化下多取代吡唑胺、三甲基硅腈（TMSCN）和醛的Strecker反应，初步探索了反应条件及醛底物的范围.共获得20个全新含氰基多取代吡唑目标物，最高收率为93.5%，并通过核磁共振氢谱（¹H NMR）、碳谱（¹³C NMR）和高分辨质谱（HRMS）确证了其结构.活性测试表明，10×10^-3 g/L浓度下，13个化合物对蚊幼虫活性为100%，5×10^-3 g/L浓度下4个化合物活性高于40%；在500×10^-3 g/L浓度下10个化合物对黏虫体现一定活性.在500×10^-3 g/L浓度下5个化合物对烟草花叶病毒具有一定钝化活性，最高活性为31.8%，4个化合物则具有保护活性，最高活性为28.3%.在50×10^-3 mg/mL浓度下，3个化合物对瓜果腐霉菌、芦笋茎枯菌、辣椒疫霉菌、水稻纹枯菌等显示一定抑制活性，其中4-[（1-氰基十二烷基）氨基]-5-乙基-N-甲基-1H-吡唑-3-甲酰胺（3t）对辣椒疫霉活性达62.3%.这表明氨基邻位具有大位阻基团的吡唑胺底物能顺利发生Strecker反应，含氰基吡唑类目标物显示多样的生物活性，具有一定的研究价值.

关键词: 多取代吡唑-4-胺, Strecker反应, ZnI₂, 含氰基多取代吡唑, 杀虫活性, 抗烟草花叶病毒活性, 杀菌活性

In order to study the Strecker reaction of multi-substituted amino armorotic heterocycles and the biological activity of the target compounds, the reaction of 3,5-disubstituted pyrazole-4-amine, TMSCN and aldehydes was realized for the first time by the catalysis of anhydrous ZnI₂ with 4Å molecular seive. The reaction condition was preliminarily optimized and the substrate scop of aldehydes was studied. 20 target compounds of cyano-containing multi-substituted pyrazoles were obtained with the highest yield of 93.5%, and the sturctures of the compounds were confirmed via ¹H NMR, ¹³C NMR and HRMS methods. Priliminary bioassay of the target compounds showed that 13 target compounds possessed 100% larvicidal activity against mosquito at a concentration of 10×10^-3 g/L, and four compounds possessed over 40% larvicidal activity at 5×10^-3 g/L, and 10 compounds poccessed weak larvicidal activity against army worm at 500×10^-3 g/L with the highest activity of 40%; five compounds were confirmed poccessed good inactivation activity against tobacco mosaic virus (TMV) in vivo with the highest inhibition rate of 31.8%, and four compounds possessed moderate host-protection activity against TMV in vivo with the highest rate of 28.3%; in addition, at a concentration of 50×10^-3 g/L, three compounds showed moderate fungicidal activity against Pythium aphanidermatum, Phomopsis asparagi, Phytophora capsic and Rhizoctonia solani in vitro. 4-((1-cyanododecyl)amino)-5-ethyl-N-methyl-1H-pyrazole-3-carboxamide (3t) possessed the highest activity against Phytophora capsic of 62.3%. All the results showed that 3,5-disubstitued pyrazole-4-amine could undergo Strecker reaction smoothly, and this study gave a useful example to explore the Strecker reaction of other multi-substituted aromatic hetreocyclic amines. Additionally, the larvicidal and anti-TMV activity of the target compounds gave some clues in design cyano-containing biological heterocycles.

Key words: multi-substituted pyrazole-4-amine, Strecker reaction, anhydrous ZnI₂, cyano-containing pyrazoles, larvicidal activity, anti-TMV activity, fungicidal activity

引用此文

苏诗淼, 朱墨, 张大强, 袁德凯. 基于Strecker反应的含氰基多取代吡唑的合成及生物活性研究[J]. 有机化学, 2019, 39(7): 2026-2034.

Su Shimiao, Zhu Mo, Zhang Daqiang, Yuan Dekai. Synthesis and Biological Activity Study of Novel Cyano-containing Multi-substituted Pyrazoles Obtained via Strecker Reaction[J]. Chin. J. Org. Chem., 2019, 39(7): 2026-2034.

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