5-嘧啶基1,2,4-噁二唑化合物的合成及抗菌活性研究
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摘要
以氰基乙酰胺为原料,经过缩合、环化、氨解和环化合成14个5-嘧啶基1,2,4-噁二唑衍生物。通过~1H NMR,~(13)C NMR,MS和元素分析确证其结构。采用菌丝生长速率法测定14个化合物在50μg·mL~(-1)时对8种植物病原真菌的活性,结果表明大部分目标产物对8种病菌具有中等抗菌活性。其中4k对猕猴桃拟茎点霉菌(Phomopsis sp.)抑制率与商品药剂嘧霉胺活性相当。
Based on 2-cyanoacetamide as raw material,fourteen 5-pyrimidinyl-1,2,4-oxadiazole derivatives were synthesized through four step reactions including condensation,cyclization,aminolysis and cyclization.The structures of these compounds were characterized by ~1H NMR,~(13)C NMR,MS and elemental analysis.The antifungal activity of them against eight phytopathogens were tested by the linear growth rate method at the concentration of 50 μg·mL~(-1).The results showed that most target compounds exhibited moderate fungicidal activity.Among of them,4 k showed the highest activity and its inhibition rate against phomopsis sp.was 84.57%,which was equivalent to pyrimethanil.
Based on 2-cyanoacetamide as raw material,fourteen 5-pyrimidinyl-1,2,4-oxadiazole derivatives were synthesized through four step reactions including condensation,cyclization,aminolysis and cyclization.The structures of these compounds were characterized by ~1H NMR,~(13)C NMR,MS and elemental analysis.The antifungal activity of them against eight phytopathogens were tested by the linear growth rate method at the concentration of 50 μg·mL~(-1).The results showed that most target compounds exhibited moderate fungicidal activity.Among of them,4 k showed the highest activity and its inhibition rate against phomopsis sp.was 84.57%,which was equivalent to pyrimethanil.
引文
[1]Yang Z B,Hu D Y,Zeng S,et al.Novel hydrazone derivatives containing pyridine amide moiety:design,synthesis,and insecticidal activity[J].Bioorg Med Chem Lett,2016,26:1 161-1 164.
[2]Liu X H,Wang Q,Sun Z H,et al.Synthesis and insecticidal activity of novel pyrimidine derivatives containing urea pharmacophore against aedes aegypti[J].Pest Manag Sci,2017,73:953-959.
[3]Chen Q,Zhu X L,Jiang L L,et al.Chem inform abstract:synthesis,antifungal activity and CoMFA analysis of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives[J].Eur J Med Chem,2008,43:595-603.
[4]Zhang J,Peng J F,Bai Y B,et al.Synthesis of pyrazolo[1,5-a]pyrimidine derivatives and their antifungal activities against phytopathogenic fungi in vitro[J].Mol Divers,2016,20:887-896.
[5]Zuo Y,Wu Q Y,Su S W,et al.Synthesis,herbicidal activity and QSAR of novel N-benzothiazolyl-pyrimidine-2,4-diones as protoporphyrinogen oxidase inhibitors[J].J Agric Food Chem,2016,64:552-562.
[6]Chen X M,Wang S H,Cui D L.The synthesis and herbicidal activity of 5-(substituted-phenyl)-4,6-dioxo-4,5,6,7-tetrahydropyrazolo[3,4-d]pyrimidines[J].J Heterocyclic Chem,2015,52:607-610.
[7]Tang S,Peng Z G,Zhang X,Cheng X Y,et al.Synthesis and biological evaluation of 12-benzyl matrinic amide derivatives as a novel family of anti-HCV agents[J].Chin Chem Lett,2016,27:1 052-1 057.
[8]Xu X J,Wang J,Yao Q Z.Synthesis and quantitative structure-activity relationship(QSAR)analysis of some novel oxadiazolo[3,4-d]pyrimidine nucleosides derivatives as antiviral agents[J].Bioorg Med Chem Lett,2015,25:241-244.
[9]Misra K,Nag A,Sonawane A.N-(2-Bromo-4-fluorophenyl)-3-(3,4-dihydroxyphenyl)-acrylamide(CPAM),a small catecholic amide as an antioxidant,anti diabetic and antibacterial compound[J].RSC Adv,2016,6:104 632-104 641.
[10]Saikia L,Roudragouda P,Thakur A J,et al.A one pot,two-step synthesis of 5-arylpyrrolo[2,3-d]pyrimidines and screening of their preliminary antibacterial properties[J].Bioorg Med Chem Lett,2016,26:992-998.
[11]Karad S C,Purohit B B,Thummar R P,et al.Synthesis and biological screening of novel 2-morpholinoquinoline nucleus clubbed with 1,2,4-oxadiazole motifs[J].Bioorg Med Chem Lett,2017,126:894-909.
[12]叶萱.1,2,4-噁二唑和1,2,4-噻二唑衍生物的合成和杀虫活性[J].世界农药,2012,34(2):17-24.
[13]陈东亮,初文毅,鄢明.1,2,4-噁二唑类化合物的合成及抗菌活性研究[J].化学应用与研究,2010,22:176-181.
[14]Zhao L,Ma X D,Chen F E.Development of two scalable syntheses of 4-amino-5-aminomethyl-2-methyl-pyrimidine:key intermediate for vitamin B1[J].Org Process Res Dev,2012,16:57-60.
[15]Wu W N,Liang W Q,Sun M Y,et al.Synthesis,fungicidal,and insecticide activity of novel substituted-N-5-cyano-pyrimidine-4-yl)-benzamides[J].J Chem Pharm Res,2014,6(11):284-290.
[16]Tarun K C,Prem D.Antifungal activity of 4-methyl-6-alkyl-2H-pyran-2-ones[J].J Agri Food Chem,2006,54(6):2 129-2 133.
[2]Liu X H,Wang Q,Sun Z H,et al.Synthesis and insecticidal activity of novel pyrimidine derivatives containing urea pharmacophore against aedes aegypti[J].Pest Manag Sci,2017,73:953-959.
[3]Chen Q,Zhu X L,Jiang L L,et al.Chem inform abstract:synthesis,antifungal activity and CoMFA analysis of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives[J].Eur J Med Chem,2008,43:595-603.
[4]Zhang J,Peng J F,Bai Y B,et al.Synthesis of pyrazolo[1,5-a]pyrimidine derivatives and their antifungal activities against phytopathogenic fungi in vitro[J].Mol Divers,2016,20:887-896.
[5]Zuo Y,Wu Q Y,Su S W,et al.Synthesis,herbicidal activity and QSAR of novel N-benzothiazolyl-pyrimidine-2,4-diones as protoporphyrinogen oxidase inhibitors[J].J Agric Food Chem,2016,64:552-562.
[6]Chen X M,Wang S H,Cui D L.The synthesis and herbicidal activity of 5-(substituted-phenyl)-4,6-dioxo-4,5,6,7-tetrahydropyrazolo[3,4-d]pyrimidines[J].J Heterocyclic Chem,2015,52:607-610.
[7]Tang S,Peng Z G,Zhang X,Cheng X Y,et al.Synthesis and biological evaluation of 12-benzyl matrinic amide derivatives as a novel family of anti-HCV agents[J].Chin Chem Lett,2016,27:1 052-1 057.
[8]Xu X J,Wang J,Yao Q Z.Synthesis and quantitative structure-activity relationship(QSAR)analysis of some novel oxadiazolo[3,4-d]pyrimidine nucleosides derivatives as antiviral agents[J].Bioorg Med Chem Lett,2015,25:241-244.
[9]Misra K,Nag A,Sonawane A.N-(2-Bromo-4-fluorophenyl)-3-(3,4-dihydroxyphenyl)-acrylamide(CPAM),a small catecholic amide as an antioxidant,anti diabetic and antibacterial compound[J].RSC Adv,2016,6:104 632-104 641.
[10]Saikia L,Roudragouda P,Thakur A J,et al.A one pot,two-step synthesis of 5-arylpyrrolo[2,3-d]pyrimidines and screening of their preliminary antibacterial properties[J].Bioorg Med Chem Lett,2016,26:992-998.
[11]Karad S C,Purohit B B,Thummar R P,et al.Synthesis and biological screening of novel 2-morpholinoquinoline nucleus clubbed with 1,2,4-oxadiazole motifs[J].Bioorg Med Chem Lett,2017,126:894-909.
[12]叶萱.1,2,4-噁二唑和1,2,4-噻二唑衍生物的合成和杀虫活性[J].世界农药,2012,34(2):17-24.
[13]陈东亮,初文毅,鄢明.1,2,4-噁二唑类化合物的合成及抗菌活性研究[J].化学应用与研究,2010,22:176-181.
[14]Zhao L,Ma X D,Chen F E.Development of two scalable syntheses of 4-amino-5-aminomethyl-2-methyl-pyrimidine:key intermediate for vitamin B1[J].Org Process Res Dev,2012,16:57-60.
[15]Wu W N,Liang W Q,Sun M Y,et al.Synthesis,fungicidal,and insecticide activity of novel substituted-N-5-cyano-pyrimidine-4-yl)-benzamides[J].J Chem Pharm Res,2014,6(11):284-290.
[16]Tarun K C,Prem D.Antifungal activity of 4-methyl-6-alkyl-2H-pyran-2-ones[J].J Agri Food Chem,2006,54(6):2 129-2 133.