新型1-(4-取代苯基)-3-[4-(4-氧香豆素基)苯基]硫脲衍生物的合成及其抑菌活性
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摘要
以4-羟基香豆素为原料,经氯化、醚化和异硫氰酸化3步反应制得中间体——4-(4-异硫氰酸酯苯氧基)香豆素(3);3与取代芳香胺经加成反应合成了9个新型的1-(4-取代苯基)-3-[4-(4-氧香豆素基)苯基]硫脲衍生物(4a~4i),其结构经1H NMR,13C NMR,IR和MS(ESI)表征。采用浑浊度法测试了4的抑菌活性。结果表明:4a、4b、4e和4f抑制烟草青枯菌活性EC50值分别为112.02、121.39、88.72和86.90μg·mL~(-1),优于噻菌铜(130.25μg·mL~(-1));4a、4b、4e和4f抑制番茄青枯菌活性EC50值分别为107.89、110.69、82.43和82.48μg·mL~(-1),优于噻菌铜(123.94μg·mL~(-1))。
The intermediate,4-(4-isothiocyanatophenoxy)-2H-chromen-2-one(3) was synthesized from 4-hydroxycoumarin via chloride,etherification,and isothiocyanate reactions. Nine novel 1-(4-substitutedphenyl)-3-{ 4-[(2-oxo-2H-chromen-4-yl) oxy]phenyl } thiourea derivatives(4a ~ 4i) were obtained by the addition reaction of 3 with substituted aromatic amines. The structures were characterized by1 H NMR,13 C NMR,IR and MS(ESI). Antibacterial activities of 4 against Xanthomonas oryzae pv. oryzae(Xoo) and Xanthomonas citri subsp. Citri(Xcc) were evaluated by the turbidimeter test. The results indicated that 4a,4b,4e and 4f showed excellent antibacterial activities against Xoo with EC50 of 112. 02,121. 39,88. 72 and 86. 90 μg·mL~(-1),respectively,which were better than that of thiodi-azole-copper(130. 25 μg·mL~(-1)). 4a,4b,4e and 4f showed excellent antibacterial activities against Xcc with EC50 of 107. 89,110. 69,82. 43 and 82. 48 μg·mL~(-1),respectively,which were better than that of thiodiazole-copper(123. 94 μg·mL~(-1)).
The intermediate,4-(4-isothiocyanatophenoxy)-2H-chromen-2-one(3) was synthesized from 4-hydroxycoumarin via chloride,etherification,and isothiocyanate reactions. Nine novel 1-(4-substitutedphenyl)-3-{ 4-[(2-oxo-2H-chromen-4-yl) oxy]phenyl } thiourea derivatives(4a ~ 4i) were obtained by the addition reaction of 3 with substituted aromatic amines. The structures were characterized by1 H NMR,13 C NMR,IR and MS(ESI). Antibacterial activities of 4 against Xanthomonas oryzae pv. oryzae(Xoo) and Xanthomonas citri subsp. Citri(Xcc) were evaluated by the turbidimeter test. The results indicated that 4a,4b,4e and 4f showed excellent antibacterial activities against Xoo with EC50 of 112. 02,121. 39,88. 72 and 86. 90 μg·mL~(-1),respectively,which were better than that of thiodi-azole-copper(130. 25 μg·mL~(-1)). 4a,4b,4e and 4f showed excellent antibacterial activities against Xcc with EC50 of 107. 89,110. 69,82. 43 and 82. 48 μg·mL~(-1),respectively,which were better than that of thiodiazole-copper(123. 94 μg·mL~(-1)).
引文
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[3]蓝健,穆金霞,贡云芸,等.新型N-(取代芳氧乙酰胺基)-N'-(1-甲基环己基酰基)硫脲及其环合产物的合成及其杀虫活性[J].合成化学,2015,23(4):305-310.
[4]李付博,万福贤,晋淸栋,等.N-(4,6-二甲基嘧啶-2-基)-N'-[3-(4-三氟甲基苯基)-5-甲基-异噁唑-4-基]酰基硫脲的合成及其除草活性[J].合成化学,2015,22(4):471-474.
[5]肖彩琴,傅颖.新型含酰基硫脲查尔酮衍生物的合成及其植物生长调节活性[J].合成化学,2015,23(9):785-790.
[6]Khare R,Sharma J,Sharma A.Synthesis,characterization,and antibacterial activity of some thiazoles derived from arylthioureas[J].Russ J Gen Chem,2016,86(3):702-707.
[7]Chetana P R,Srinatha B S,Somashekar M N,et al.Synthesis,spectroscopic characterisation,thermal analysis,DNA interaction and antibacterial activity of copper(I)complexes with N,N'-disubstituted thiourea[J].J Mol Struc,2016,1106:352-365.
[8]Ghorab M M,Alsaid M S,El-Gaby M S A,et al.Biological evaluation of some new N-(2,6-dimethoxypyrimidinyl)thioureido benzenesulfonamide derivatives as potential antimi-crobial and anticancer agents[J].Eur J Med Chem,2016,124:299-310.
[9]时蕾,张伶俐,鹿泽华,等.双吲哚马来酰亚胺硫脲化合物的合成及抗肿瘤活性[J].化学通报,2016,79(12):1150-1155.
[10]肖春芬,陈辉芳,何笑薇,等.新型3-芳基香豆素类化合物的合成及其抗肿瘤活[J].合成化学,2015,23(5):376-381.
[11]Aws M,Hamdy A M,Khaddour Z,et al.Synthesis of arylated coumarins by Suzuki-Miyaura cross-coupling reactionwqeeeqqs and anti-HIV activity[J].Bioorg Med Chem,2016,24(21):5115-5126.
[12]王诚,江润生,冯锋,等.4-羟基香豆素Schiff碱的合成及其抑菌活性[J].化学试剂2008,30(12):935-936.
[13]Roussaki M,Zelianaios K,Kavetsou E.et al.Structural modifications of coumarin derivatives:Determination of antioxidant and lipoxygenase(LOX)inhibitory activity[J].Bioorg Med Chem,2014,22(23):6586-6594.
[14]刘斌,谢龙观,徐效华,等.3-苯甲酰基-4-羟基香豆素衍生物的合成,晶体结构及其除草活性研究[J].有机化学,2011,31(12):2067-2073.
[15]Chen M H,Tang B C,Zhang X M.et al.Synthesis and antibacterial activity evaluation of novel(E)-4-(4-((arylid-ene)amino)phenoxy)coumarin derivatives[J].J Heterocyclic Chem,2016,(in press)DOI10.1002/jhet.2691.
[16]Xu W M,Han F F,He M,et al.Inhibition of tobacco bacterial wilt with sulfone derivatives containing an1,3,4-oxadiazole moiety[J].J Agric Food Chem,2012,60(4):1036-1041.