1-芳基-3-(3-(4-氧香豆素基)苯基)硫脲衍生物的合成及抑菌活性

doi:10.11944/j.issn.1000-0518.2017.07.160427

摘要/Abstract

摘要：

为了筛选出具有较高抑菌活性的含香豆素的硫脲类衍生物,本文以4-羟基香豆素为原料,经氯化、醚化、异硫氰酸化和加成反应合成了一系列1-芳基-3-(3-(4-氧香豆素基)苯基)硫脲衍生物,其结构经红外光谱(IR)、核磁共振谱(NMR)和质谱(MS)等技术手段进行了表征。结果表明,目标化合物对水稻白叶枯菌和柑橘溃疡菌均具有较好的抑制活性。其中化合物4k、4l、4m和4n抑制水稻白叶枯菌活性EC₅₀值分别为137.42、131.05、129.23和117.43 mg/L,优于对照药剂噻菌铜的活性 (195.24 mg/L);化合物4k、4l、4m和4n抑制柑橘溃疡菌活性EC₅₀值分别为97.02、94.31、102.28和90.52 mg/L,优于噻菌铜的活性(120.25 mg/L)。

关键词: 香豆素, 硫脲类衍生物, 合成, 抑菌活性

Abstract:

In order to develop thiourea derivatives with antibacterial activities, a series of novel 1-aryl-3-(3-((2-oxo-2H-chromen-4-yl)oxy)phenyl)thiourea derivative was synthesized from 4-hydroxycoumarin via chlorination, etherification, isothiocyanate formation and addition reactions. The structures of the title compounds were characterized by infrared spectroscopy(IR), nuclear magnetic resonance spectrocopy(NMR) and mass spectrometry(MS). The results show that title compounds exhibit excellent antibacterial activities against Xanthomonas oryzae pv. oryzae(Xoo) and Xanthomonas citri subsp. Citri(Xcc). Among of them, compounds 4k, 4l, 4m and 4n show excellent antibacterial activities against Xoo, with the EC₅₀ values 137.42, 131.05, 129.23 and 117.43 mg/L, respectively, which were better than that of the control agent thiodiazole-copper(195.24 mg/L). Compounds 4k, 4l, 4m and 4n display considerable antibacterial activities against Xcc, with the EC₅₀ values of 97.02, 94.31, 102.28 and 90.52 mg/L, respectively, which are better than that of thiodiazole-copper(120.25 mg/L).

Key words: coumarin, thiourea derivatives, synthesis, antibacterial activities

陈美航, 张迅, 王晓斌, 陈仕学, 舒华. 1-芳基-3-(3-(4-氧香豆素基)苯基)硫脲衍生物的合成及抑菌活性[J]. 应用化学, 2017, 34(7): 774-782.

CHEN Meihang, ZHANG Xun, WANG Xiaobin, CHEN Shixue, SHU Hua. Synthesis and Antibacterial Activity of 1-Aryl-3-(3-((2-oxo-2H-Chromen-4-yl)oxy)phenyl)thiourea Derivatives[J]. Chinese Journal of Applied Chemistry, 2017, 34(7): 774-782.

参考文献

[1]	CHEN Liang,LIU Junli. The New Tendency of Crops Bacterial Diseases Occur[J]. Pestic Mark News,2010,20(31):48-50(in Chinese). 陈亮,刘君丽. 农作物细菌性病害发生的新趋势[J]. 农药市场信息,2010,20(31):48-50.
[2]	ZUO Jinglong,JIANG Guixia. Bacterial Disease Prevention and Control of Major Chemical Reagents[J]. Jilin Veget,2016,3:21-22(in Chinese). 左经龙,姜桂霞. 细菌性病害主要化学防治药剂[J]. 吉林蔬菜,2016,3:21-22.
[3]	ZHOU Yuping,YANG Zhengyin,YU Hongjuan,et al.Syntheses, Characterization and Bacteriostatic Activities of 1-Phenyl-3-methyl-4-benzoylpyrazolone-5-thiosemicarbazone and Its Rare Earth Complexes[J]. Chinese J Appl Chem,1999,16(6):37-41(in Chinese). 周毓萍,杨正银,于红娟,等. 1-苯基-3-甲基-4-苯甲酞基吡唑酮-5-缩氨基硫腮稀土配合物的合成、表征及抑菌活性[J]. 应用化学,1999,16(6):37-41.
[4]	SU Guifa,HE Lini,QIN Jiangke,et al.Synthesis and Antibacterial Activity of 1-Dehyoabicticacy-3-Aroylthiosem-Icarbazides Compounds and Their 1,3,4-Thiadiazole Derivatives[J]. Chinese J Appl Chem,2008,25(7):803-807(in Chinese). 苏桂发,霍丽妮,覃江克,等. 1-脱氢松香酰基-3-芳酰胺基硫脲及其1,3,4-噻二唑类衍生物的合成及抑菌活性[J]. 应用化学,2008,25(7): 803-807.
[5]	Lu A D,Wang Z W,Zhou Z H,et al.Application of “Hydrogen Bonding Interaction” in New Drug Development: Design, Synthesis, Antiviral Activity, and SARs of Thiourea Derivatives[J]. J Agric Food Chem,2015,63(5):1378-1384.
[6]	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 Antimicrobial and Anticancer Agents[J]. Eur J Med Chem,2016,124:299-310.
[7]	Yapati H,Devineni S R,Chirumamilla S,et al.Synthesis, Characterization and Studies on Antioxidant and Molecular Docking of Metal Complexes of 1-(Benzo[d]thiazol-2-yl)thiourea[J]. J Chem Sci,2016,128(1):43-51.
[8]	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 Struct,2016,1106:352-365.
[9]	Kadir M A,Ramli R, Yusof M S M, et al. Synthesis, Spectroscopic Studies and Antibacterial Activity of New Lauroyl Thiourea Amino Acid Derivatives[J]. Asian J Chem,2016,28(3):596-600.
[10]	Khare R,Sharma J,Sharma A.Synthesis, Characterization, Antibacterial Activity of Some Thiazoles Derived from Allylthioureas[J]. Russ J Gen Chem,2016,86(3):702-707.
[11]	WANG Cheng,WANG Runsheng,FENG Feng,et al.Synthesis of a New Schiff Base Containing 4-Hydroxy Coumarin and Characterization of Its Antibacterial Activity[J]. Chem Reag,2008,30(12):935 936(in Chinese). 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.
[12]	LIU Bin,XIE Longguan,XU Xiaohua,et al.Synthesis, Crystal Structure and Herbicidal Activity of 3-Benzoyl-4-hydroxycoumarin Derivative[J]. Chinese J Org Chem,2011,31(12):2067-2073(in Chinese). 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.
[13]	Cao D,Liu Y B,Yan W,et al.Design, Synthesis, and Evaluation of in Vitro and in Vivo Anticancer Activity of 4-Substituted Coumarins:A Novel Class of Potent Tubulin Polymerization Inhibitors[J]. J Med Chem,2016,59(12):5721-5739.
[14]	Aws M,Hamdy A M,Khaddour Z,et al.Synthesis of Arylated Coumarins by Suzuki-Miyaura Cross-Coupling. Reactions and Anti-HIV Activity[J]. Bioorg Med Chem,2016,24(21):5115-5126.
[15]	Buzad C,Doherty M F. Design of Three-Component Kioetically Controlled Reactive Distillation Columus Using Fixed-Point Methods[J]. Chem Eng Sci,1994,49(12):1947-1963.
[16]	XU Cuilian,CHEN Gang,XIA Baigen,et al.Synthesis and Antibacterial Activity of Thiosemicarbazone Compounds Containing Coumarin-Skeleton[J]. Chem Bull,2009,9:815-819(in Chinese). 徐翠莲,陈钢,夏百根,等. 含香豆素骨架的缩氨基硫脲化合物的合成和抑菌活性研究[J]. 化学通报,2009,9:815-819.
[17]	Chen M H,Tang B C,Zhang X,et al.Synthesis and Antibacterial Activity Evaluation of Novel (E)-4-(4-((arylid-ene)amino)phenoxy)coumarin Derivatives[J]. J Heterocycl Chem,2016,(in press),DOI
[18]	Rao M L N,Kumar A. Pd-Catalyzed Chemo-Selective Mono-Arylations and Bis-Arylations of Functionalized 4-Chlorocoumarins with Triarylbismuths as Threefold Arylating Reagents[J]. Tetrahedron,2014,70(39):6995-7005.
[19]	Xu W M,Han F F,He M,et al.Inhibition of Tobacco Bacterial Wilt with Sulfone Derivatives Containing an 1,3,4-Oxadiazole Moiety[J]. J Agric Food Chem,2012,60(4):1036-1041.