6-溴-1-异丙烯基-1H-咪唑[4,5b]吡啶-2-酮酰胺衍生物的合成及其抑菌活性研究

Synthesis and antifungal activity of 6-bromo-1-isopropenyl-1H-imidazo[4,5b]pyridine-2-one derivatives

【目的】研究6-溴-1-异丙烯基-1 H-咪唑[4,5b]吡啶-2-酮酰胺衍生物抑制真菌活性的构效关系,为病原菌的防治提供参考依据。【方法】以5-溴-2,3-二氨基吡啶为原料,经乙酰乙酸乙酯环化制得中间体化合物6-溴-1-异丙烯基-1 H-咪唑[4,5b]吡啶-2-酮,再按照目标化合物合成路线设计合成6-溴-1-异丙烯基-1 H-咪唑[4,5b]吡啶-2-酮酰胺衍生物。通过核磁共振、质谱以及元素分析对目标化合物进行结构表征。以嘧菌酯为对照,采用菌丝生长速率法测定目标化合物对小麦赤霉病菌(Fusarium graminearum)、玉米弯孢霉病菌(Curvularia lunata)、棉花枯萎病菌(Fusarium oxysporumf.sp.vasinfectum)、茄子黄萎病菌(Verticillium dahlia)、西瓜枯萎病菌(Fusarium oxysporum)和苹果炭疽病菌(Colletotrichum gloeosporioides)的抑菌活性。【结果】合成了17个6-溴-1-异丙烯基-1 H-咪唑[4,5b]吡啶-2-酮酰胺衍生物,其中脂肪羧酸酰胺衍生物10个(B01-B10),芳香羧酸酰胺衍生物6个(B11-B16),杂环羧酸酰胺衍生物1个(B17)。抑菌活性测定结果表明,17个目标化合物对供试病原真菌均有一定的抑菌活性,其中化合物B01,B03-B06和B13在100μg/mL质量浓度下对部分供试病原真菌菌丝生长有明显的抑制作用,尤以化合物B06的抑菌活性最为突出,抑制率均可达到70%以上,其对6种供试植物病原真菌的EC50值分别为8.23,49.32,21.45,24.87,36.40和28.65μg/mL,均高于对照药剂嘧菌酯。【结论】6-溴-1-异丙烯基-1 H-咪唑[4,5b]吡啶-2-酮衍生物对6种供试病原真菌均具有一定的抑制活性,该类化合物的结构具有进一步改造研究的价值。

【Objective】The paper explored the relationship between structure of 6-bromo-1-isopropenyl-1 H-imidazo[4,5 b]pyridine-2-one amide derivatives and the antifungal activities to provide reference for fungal control.【Method】Starting from 5-bromopyridine-2,3-diamine and ethyl acetoacetate,a series of 6-bromo-1-isopropenyl-1 H-imidazo[4,5 b]pyridine-2-one derivatives were synthesized.The structures of the synthesized compounds were confirmed by 1 H NMR,ESI-MS and elemental analysis.Growth rate method was adopted to test the antifungal activities of these compounds against Fusarium graminearum,Curvularia lunata,Fusarium oxysporumf.sp.vasinfectum,Verticillium dahliae,Fusarium oxysporumand Colletotrichum gloeosporioidesin comparison with azoxystrobin.【Result】Seventeen compounds were synthe-sized,containing ten aliphatic acid derivatives（B01-B10）,six aromatic carboxylic acid derivatives（B11-B16）and one heterocyclic carboxylic acid derivative（B17）.When the mass concentration was 100μg/mL,antifungal activity tests indicated that B01,B03-B06,and B13 exhibited significant inhibitory activities against the mycelial growth of tested fungi.B06 had the best inhibition rate of70% and its EC50 values were 8.23,49.32,21.45,24.87,36.40 and 28.65μg/mL,respectively,which were higher than those of azoxystrobin.【Conclusion】The synthesized 6-bromo-1-isopropenyl-1 H-imidazo[4,5 b]pyridine-2-one amide derivatives had antifungal activities against the mycelial growth of the six fungi,and should be further studied.