一些噻二唑衍生物的合成及抑菌活性研究
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摘要
以硫代氨基脲、甲酸、取代苯甲酸以硫代氨基脲、甲酸、取代苯甲酸为原料,通过脱水环化、Knoevenagle缩合反应等步骤,得到一类具有噻唑环和噻唑啉酮双杂环结构的化合物6a～6h。此外,将中间体4a～4h与三氯吡啶醇钠反应,得到另一类具有噻唑环和三氯吡啶醇结构的新型化合物7a～7g。合成的终产物中,有9个化合物为新化合物。采用IR、NMR等方法对合成化合物进行了结构表征,并且利用生长速率法对目标产物的植物菌类抑菌活性进行测试,初步结果表明,部分化合物具有一定的抑菌活性,化合物6d对稻瘟病菌(Fusarium oxysporumf.sp.cubense)和番茄早疫病菌(Alternariasolani)具有良好的活性,在浓度为50 mg·L~(-1)时,抑菌率达到80%以上。
Using thiosemicarbazide,formic acid and substituted benzoic acid as starting materials,through dehydration and Knoevenagle reaction,a series of compounds containing both thiazole and thiazolinone with double heterocyclic structures were synthesized.In addition,another new type of compounds 7a～7g containing both thiazole and trichloropyridine double heterocyclic structures were synthesized.The structures of all the products were characterized by IR,NMR,and nine of them were new compounds.The antimicrobial activity of the target products was evaluated by the growth rate method.The results showed that some compounds displayed distinct inhibitory activity.Especially,compound 6d could effectively inhibit Fusarium oxysporumf.sp.cubense and Alternariasolani better than other compounds,and the inhibitory rate was above 80% at the concentration of 50 mg·L~(-1).
Using thiosemicarbazide,formic acid and substituted benzoic acid as starting materials,through dehydration and Knoevenagle reaction,a series of compounds containing both thiazole and thiazolinone with double heterocyclic structures were synthesized.In addition,another new type of compounds 7a～7g containing both thiazole and trichloropyridine double heterocyclic structures were synthesized.The structures of all the products were characterized by IR,NMR,and nine of them were new compounds.The antimicrobial activity of the target products was evaluated by the growth rate method.The results showed that some compounds displayed distinct inhibitory activity.Especially,compound 6d could effectively inhibit Fusarium oxysporumf.sp.cubense and Alternariasolani better than other compounds,and the inhibitory rate was above 80% at the concentration of 50 mg·L~(-1).
引文
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[2]崔建国,申海斌,何冬梅,等.O,O’-二乙基-(5-芳基-1,3,4-噻二唑-2-)硫代磷酰胺化合物的合成及生物活性研究[J].化学研究与应用,2018,30(12):1 967-1 972
[3]李娜,魏学,范会涛,等.2-氰基-3-(4-甲基苯并[d]噻唑-2-氨基)-3-苯基丙烯酸酯类化合物的合成及抗病毒活性[J].有机化学,2011,31(8):1 300-1 311.
[4]严曼,石德清.N-(4,6-二取代嘧啶-2-基)-N′-[1-(杂芳基)甲基-5-甲基-1H-1,2,3-三唑基-4-甲酰基]硫脲的合成与除草活性研究[J].有机化学,2008,28(4):736-740.
[5]宋新建,冯桂荣,陈传兵,等.N-[5-(4-吡啶基)-1,3,4-噻二唑-2-基]-N′-芳酰基脲的合成与生物活性[J].有机化学,2005,25(12):1 587-1 590.
[6]Zine H,Rifai L A,Koussa T,et al.The mononuclear nickel(Ⅱ)complex bis(azido-κN)bis[2,5-bis(pyridin-2-yl)-1,3,4-thladlazole-κ2N2,N3]nlckel(Ⅱ)protects tomato from verticillium dahliae by inhibiting the fungal growth and activating plant defenses[J].Pest Manage Sci,2016,73:188-197.
[7]Havrylyuk D,Zimemkovsky B.Synthesis of novel thiazolone-based compounds containing pyrazoline moiety and evaluation of their anticaner activity[J].Eur J Med Chem,2009 2009,44(4):1 396-1 404.
[8]Havrylyuk D,Mosula L,Zimemkovsky B.Synthesis and anticancer activity evaluation of 4-thiazolidinones containing benzothiazole moiety[J].Eur J Med Chem,2010 2010,45(11):5 012-5 021.
[9]Zhou H Y,Wu S H,Zhai S M,et al.Design,synthesis,cytoselective toxicity,structure-activity relationships,and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells[J].J Med Chem,2008,51(5):1 242-1 251.
[10]Geronikaki A A,Lagunin A A.Computer-aided discovery of antiinflammatory thiazolidinones with dual cyclooxygenaselipoxygenase inhibition[J].J Med Chem,2008,51(6):1 601-1 609.
[11]Liesen A P,Aquino T M,Carvalho C S,et al.Synthesis and evaluation of anti-toxoplasma gondii and antimicrobial activities of thiosemicarbazides,4-thiazolidinones and 1,3,4-thiadiazoles[J].Eur J Med Chem,2010,45(9):3 685-3 691.
[12]Vicini P,Geronikaki A,Anastasia K,et al.Synthesis and antimicrobial activity of novel 2-thiazolylimino-5-arylidene-4-thiazolidinones[J].Bioorg Med Chem,2006,14(11):3 859-3 864.
[13]Vicini P,Geronikaki A,Incerti M,et al.2-Heteroaryl-imino-5-benzylidene-4-thiazolidinones analogues of 2-thiazolylimino-5-benzyl-idene-4-thiazolidinones with antimicrobial activity:Synthesis and structure activity relationship[J].Bioorg Med Chem,2008,16(7):3 714-3 724.
[14]Aakash D,Sandeep J,Prabodh C,et al.Synthesis of 2-(aryl)-5-(arylidene)-4-thiazolidinone derivatives with potential analgesic and anti-inflammatory activity[J].Med Chem Res,2012,21:652-659.
[15]Dmytro H,Ludmyla M,Borys Z,et al.Synthesis and anticancer activity evaluation of 4-thiazolidinones containing benzothiazole moiety[J].Eur J Med Chem,2010,45:5 012-5 021.
[16]孟祥武,陆丰平,赵华绒.2-氨基-4-塞唑啉酮的高效合成和晶体结构[J].化学学报,2011,69(19):2 281-2 286.
[17]Noolvi M N,Patel H M,Singh N,et al.Synthesis and anticancer evaluation of novel 2-cycloptopylimidazo[2,1-b][1,3,4]-thiadiazole derivatives[J].Eur J Med Chem,2011,43(3):4 411-4 418.
[18]赵丹凤,陈霄榕,邓涛.3,5,6-三氯吡啶-2-醇钠的合成研究[J].河北工业大学学报,2012,41(1):48-51.
[19]周德锋,耿丽文,聂开晟,等.新杀菌剂氯啶菌酯及其合成工艺[J].农药研究,2008,(8):13-14.
[20]刘玉婷,周英,尹大伟.2-氨基-5-芳基-1,3,4-噻二唑的合成[J].精细石油化工,2011,28(1):61-63.
[21]Li Z,Zhang W,Liu Q,et al.Cettoerpper-mediated sequential C-N and N-N bond formation:facile synthesis of symmetrical 1,2,4-triazoles[J].Synlett,2013,24:2 735-2 739.
[22]Sanmati K Jain,Pradeep Mishra.Synthesis and evaluation of some 2-[(substituted)ethanoyl]amino-5-aryl-1,3,4-thiadiazoles as diuretic agents[J].Asian J Chem,2011,23(3):1 305-1 308.
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