CN115385917B - 一类色胺酮7位或9位取代芳香硫醚衍生物、其制备方法及应用 - Google Patents
一类色胺酮7位或9位取代芳香硫醚衍生物、其制备方法及应用 Download PDFInfo
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- CN115385917B CN115385917B CN202210948047.5A CN202210948047A CN115385917B CN 115385917 B CN115385917 B CN 115385917B CN 202210948047 A CN202210948047 A CN 202210948047A CN 115385917 B CN115385917 B CN 115385917B
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
本发明公开了色胺酮7位或9位取代芳香硫醚两个系列衍生物,所发明的化合物作为防治植物病原菌细菌的用途,所述衍生物的通式如(Ⅰ)或(Ⅱ)所示。该通式所示的化合物植物病原菌细菌活性测试结果显示,对水稻白叶枯病菌(Xanthomonas oryzaepv.oryzae,Xoo)、柑橘溃疡病菌(Xanthomonascampestrispv.citri,Xac)、猕猴桃溃疡菌(seudomonassyringaepv.ac tinidiae,Psa)等具有较好的抑菌效果,可用于开发新型农用杀菌剂,
Description
技术领域
本发明涉及化工技术领域,具体来说涉及一类色胺酮7位或9位取代芳香硫醚衍生物的制备方法及其在抑菌活性方面的应用。
背景技术
色胺酮(Tryptanthrin)为吲哚喹唑啉类生物碱,是中药青黛和大青叶及其药用植物马蓝(Strobilanthescusia)、蓼蓝(Polygonum tinctorum Lour)和菘蓝(IsatisEinetorial)的主要成分之一,在中药板蓝根以及微生物发酵液和海洋微生物中均有所发现。色胺酮具有抗肿瘤、抗炎、抗菌、抗冠状病毒(NL63)和抗植物病毒(TMV)等广泛的生物活性。尤其抗细菌活性方面较为突出,具有拮抗枯草芽孢杆菌(B.subtilis)、埃希氏杆(E.Castellani)、大肠杆菌(E.coli)和结核分枝杆菌(M.tuberculosis)的等抑菌活性。
细菌性病害是作物种植常见病害,但其严重危害农产品的质量和安全,构成全球性粮食安全问题。例如水稻白叶枯病菌(Xanthomonas oryzaepv.oryzae)是一类世界性的重要细菌病害。
以色胺酮为先导化合物对其进行结构修饰,合成色胺酮硫醚类衍生物并在植物病原菌抑菌活性方面进行深入研究,为高效低毒绿色农药的开发提供了一种新的思路。
色胺酮类衍生物生物活性的研究进展如下:
2020年,Jana等[JanaH.M,Bianka M.Peter E.Uta-ChristinaH.,CorneliaW.Tryptanthrin promotes keratinocyte and fbroblast responses in vitroafter infection with Trichophyton benhamiae DSM6916[J]Sci.Rep.2020,10,1863.]发现植物源生物碱色胺酮对酵母和皮肤植物具有较强的抑菌活性,利用体外皮肤真菌病模型分析其在感染条件下的生物活性,该模型使用了被T.benhamiaeDSM6916感染的成纤维细胞和角质形成细胞,分析包括细胞活力的测定,对先天免疫反应的影响,以及促炎细胞因子/趋化因子的表达和分泌,以及各种抗菌肽(AMP)、toll样受体(TLR)2和增殖标志物MKI67的表达。
2020年,Hao等,[Hao,Y.N.,Guo,J.C.,Wang,Z.W.,Liu,Y.X.,Li,Y.Q.,Ma,D.J.,&Wang,Q.M.Discovery of Tryptanthrins as Novel Antiviral and Anti-Phytopathogenic-Fungus Agents.[J]J.Agric.Food Chem.2020,68,5586-5595]设计、合成了一系列色胺酮衍生物,对烟草花叶病毒(TMV)和植物性病原真菌进行了活性评价。发现色胺酮衍生物对TMV具有较高的抗病毒活性,大多数化合物抗TMV活性优于商品药利巴韦林。进一步的杀菌活性试验表明,色胺酮具有广谱杀菌活性,尤其对苹果轮纹病菌具有较好的抑菌选择性,为其在植物保护领域的应用奠定了基础。。
2021年,Chi等[ChiJ.L,YaL.C.,YuL.Y,YingL.C.Natural alkaloidtryptanthrin exhibits novel anticryptococcal activity.[J]Medical Mycology2021,59,545-556].研究发现色胺酮对隐球菌的最低抑制浓度(MIC)为2μg/ml,对红色毛癣菌的最低抑制浓度(MIC)为8μg/ml。进一步分析表明,色胺酮在高温下仍具有较强的抑菌和抗真菌活性。深入研究发现色胺酮与钙转运体(Pmc1)和蛋白激酶a信号通路等多种转运体和信号通路相关,通过干扰隐球菌的细胞周期和信号通路发挥了抗真菌活性。
硫醚类衍生物生物活性的研究进展如下:
2022年,Zhang等[Zhang C.Y.,Yu R.J.,Wang L.Q.,Huang H.Y.,Wang J.T.,LiaoX.W.,Duan X.M.,Xiong Y.S.Design,synthesis,and evaluation of aryl-thioetherruthenium polypyridine complexes:A multi-target antimicrobial agents againstgram-positive bacteria[J]Eur.J.Med.Chem.,2022,240,114562]设计、合成了4种新型钌硫醚类配合物,并对其进行了杀菌活性评估,发现体外对金黄色葡萄球菌(S.aureus)有较强的抑制活性。抗菌机理研究表明Ru(II)-1通过细菌细胞膜的通透性和去极化作用破坏细菌细胞膜的完整性,并与细菌DNA相互作用产生大量的ROS来杀死细菌,具有治疗革兰氏阳性细菌感染的潜力。
2019年,Wang等[Wang P.Y.,Wang M.W.,Zeng D.,Xiang M.,Rao J.R.,Liu Q.Q.,Liu L.W.,Wu Z.B.,Li Z.,Song B.A.,Yang S.Rational Optimization and ActionMechanism of Novel Imidazole(orImidazolium)-Labeled 1,3,4-OxadiazoleThioethers as PromisingAntibacterial Agents against Plant BacterialDiseases[J]J.Agric.Food Chem.2019,67,3535–3545]将咪唑和1,3,4-恶二唑活性基团进行分子拼接,设计合成了1,3,4-恶二唑硫醚类衍生物。活性研究发现,部分化合物对植物病原菌白叶枯病菌(Xanthomonas oryzaepvoryzae)和柑桔白叶枯病菌(Xanthomonasaxonopodispvcitri)的EC50最小值为0.734和1.79μg/mL,均优于商品化药剂。通过扫描电子显微镜、透射电子显微镜和荧光显微镜图像的浓度依赖性进一步阐述了作用机理,可作为开发商品化药物的前景指标进一步探索和开发。
发明内容
本发明的目的之一提供了一类色胺酮7位或9位取代芳香硫醚衍生物。
本发明还有一目的是提供了一种含有上述化合物或其异构体,或其盐类,或其溶剂化合物及组合物。
本发明还有一目的是提供了上述化合物或所述组合物的用途。
本发明还有一目的是提供了上述化合物或所述组合物的防治农业植物细菌病害方法。
为实现上述目的,本发明采用了下述技术方案:
一类色胺酮7位或9位取代芳香硫醚衍生物,该类化合物具有如通式(Ⅰ)或(Ⅱ)所示的结构:
其中,
R1选自任意取代或未取代的芳基结构,任意取代或未取代的芳杂环基结构。
R2为独立地选自氢,硝基,C1-C4烷氧基,C1-C4烷烃基,卤素,三氟甲基,三氟甲氧基,氨基,羟基,氰基,羧基,甲砜基,磺酸基。
R3为分别独立地选自氢,硝基,C1-C4烷氧基,C1-C4烷烃基,卤素,三氟甲基,三氟甲氧基,氨基,羟基,氰基,羧基,甲砜基,磺酸基,或上述取代基团任意组合的二取代、三取代、四取代的衍生物。
进一步的,R1为取代或未取代苯基,或,取代或未取代吡啶或嘧啶。所述的取代苯基的取代基为卤素;所述的取代吡啶或嘧啶的取代基为三氟甲基。
所述的一类色胺酮7位或9位取代芳香硫醚衍生物,选自下述化合物:
本发明还提供了所述的一类色胺酮7位或9位取代芳香硫醚衍生物的制备方法,其包括下述步骤:
一类组合物,含有所述的化合物或其立体异构体或其盐类或其溶剂化合物,以及农业上用的助剂或杀菌制剂。
所述的化合物或其立体异构体或其盐类或其溶剂化合物的组合物,在农业病菌病害药物中的应用。优选地,所述农业病害为植物细菌性病害;更优选地,所述农业病害为植物叶枯病和溃疡病;最优选地,所述农业病害为水稻白叶枯病、柑橘溃疡病和猕猴桃溃疡病。
此处用到的术语“取代的”指的是在指定原子或基团上的任意一个或多个氢原子。
术语“芳基”指的是在环部分具有6到12个碳原子的单环或双环芳香烃基,如苯基,所有可被取代的。
术语“卤素”或“卤素原子”指的是氟、氯、溴和碘。
术语“芳杂环基”指的是取代和非取代芳香5或6元单环基团,9-或10-元双环基团,和11到14元三环基团,在至少一个环中具有至少一个杂原子(O,S或N),所述含杂原子的环优选具有1、2或3个选自O、S和N中的杂原子。
如果没有其它说明,本发明的化合物理解为包括游离态和其盐。术语“盐”表示以无机和/或有机酸和碱形成酸式和/或碱式盐。
通过采用上述技术方案,本发明以取代苯胺为起始原料,合成一系列各种取代的靛红衍生物中间体;将取代靛红衍生物在二氯甲烷中通过间氯过氧苯甲酸室温下氧化,制备取代的靛红酸酐衍生物;取代靛红与取代靛红酸酐通过优化的Bergman缩合反应,合成色胺酮类衍生物;最后,以碳酸钾为催化剂在NMP溶剂作用下加热搅拌获得色胺酮7位或9位取代芳香硫醚衍生物。通过对植物病原细菌的活性测试结果,发现该类化合物还具较好的抑制植物病菌生物活性,针对水稻白叶枯病(Xoo)、柑橘溃疡病(Xac)和猕猴桃溃疡病(Psa)具有良好的抑制作用,为以天然源生物碱色胺酮为先导化合物基础,开发高效低毒的绿色农药提供一种研究方向。
实施例
下面通过实施例对本发明作进一步说明。应该理解的是,本发明实施例所述方法仅仅是用于说明本发明,而不是对本发明的限制,在本发明的构思前提下对本发明制备方法的简单改进都属于本发明的范围。实施例中用到的所有原料和溶剂均为市售产品。
实施例1
(1)取代靛红的制备
在500mL圆底三口烧瓶中,事先加入220mL蒸馏水,加热至50℃,添加无水硫酸钠(0.1mol)搅拌至完全溶解,用5%的稀盐酸完全溶解相应的苯胺溶液(0.1mol),然后逐滴滴加到反应体系中,继续滴加盐酸羟胺水溶液(0.3mol),回流5-8h,TLC监测,待反应完全,冷却,真空抽滤,干燥,得到反应式中间体化合物3。
在250mL圆底三口烧瓶中,将中间体化合物3(0.1mol)分批次加入到90%的浓硫酸中,90℃加热搅拌3-5h后冷却至室温,快速搅拌下加入500mL的冰水混合物中,关环30min,抽滤,水洗,真空抽滤,干燥,获得各种取代靛红衍生物5。
(2)取代靛红酸酐的制备
在250mL圆底三口烧瓶中,将取代靛红衍生物(0.1mol)悬浮于二氯甲烷中,在冰浴条件下分批次加入间氯过氧苯甲酸(0.12mol),然后室温搅拌3-5h,TLC监测,反应结束后,过滤,饱和碳酸氢钠洗涤,得到浅黄色固体,产率70%-85%。
(3)卤素取代色胺酮的制备
在250mL圆底三口烧瓶中,将上述制备的取代靛红(0.1mol)和取代靛红酸酐(0.1mol)在甲苯溶剂中以三乙胺为催化剂,加热回流3-5h,TLC监测,反应结束后,旋干溶剂,柱层析分离,得到黄色固体,产率65%-90%。
(4)目标化合物色胺酮7位或9位取代芳香硫醚衍生物的制备
在50mL圆底三口烧瓶中,加入取代色胺酮化合物(0.01mol),加入反应溶剂N,N-二甲基甲酰胺(20mL),以碳酸铯(0.03mol)为催化剂,70℃加热搅拌5-8h后冷却至室温,加入纯水2.0mL,静置30min,真空抽滤,干燥,柱层析分离,得到浅黄色固体,产率50%-80%。
其他目标化合物合物色胺酮7位或9位取代芳香硫醚衍生物,采用相应的原料或取代基,参照实施例步骤(4)的合成方法。
合成的部分色胺酮7位或9位取代芳香硫醚衍生物的结构及核磁共振氢谱和高分辨质谱数据如表1所示,物化性质如表2所示。
表1部分化合物的核磁共振氢谱、碳谱及高分辨质谱数据。
表1色胺酮7位或9位取代芳香硫醚衍生物1H NMR和ESI-HRMS数据
表2部分目标化合物的理化性质
表2色胺酮7位或9位取代芳香硫醚衍生物的理化性质
化合物编号 | 物理形态 | 产率(%) | 熔点(℃) |
1 | 黄色固体 | 67.9 | >300 |
2 | 黄色固体 | 79.2 | 232-233 |
3 | 黄色固体 | 76.1 | 289-291 |
4 | 黄色固体 | 62.7 | 269-270 |
5 | 橘黄色固体 | 54.6 | 276-277 |
6 | 橘黄色固体 | 52.5 | 255-257 |
7 | 橘黄色固体 | 60.3 | 256-257 |
8 | 橘黄色固体 | 55.9 | 211-213 |
9 | 橘黄色固体 | 53.0 | 267-269 |
10 | 黄色固体 | 64.3 | 234-235 |
11 | 黄色固体 | 65.5 | 281-282 |
12 | 黄色固体 | 54.1 | 268-270 |
13 | 黄色固体 | 50.7 | 218-220 |
药理实施例1:
抗植物病原菌性测试。
采用浊度法测试色胺酮7位或9位取代芳香硫醚衍生物对植物病原菌细菌的抑制率,测试病原菌为水稻白叶枯病菌(Xoo)、柑橘溃疡病菌(Xac)和猕猴桃溃疡病菌(Psa)。空白对照为DMSO,阳性对照为叶枯唑和噻菌酮。恒温摇床在28℃和180rpm条件下,将Xoo、Xac和Psa病原菌接种于固体培养基(NA)中,使用时在28℃/180rpm恒温摇床中振荡培养到对数生长期备用。将被测试化合物和阳性对照药配置不同浓度的含毒NB液体培养基,分别加入40μL生长至对数期的含植物病原菌的NB培养基液体,在28℃/180rpm恒温摇床中振荡,水稻白叶枯病菌培养约36小时,猕猴桃溃疡菌和柑橘溃疡菌培养约48小时,待摇床中对照组的OD值在生长对数期时,通过酶标仪在595nm处分别测定空白对照组、阳性对照药和化合物OD值。
校正OD值和抑制率的计算公式如下:
校正OD值=含菌培养基OD值-无菌培养基OD值。
抑制率%=[(校正后对照培养基菌液OD值-校正含毒培养基OD值)/校正后对照培养基菌液OD值]×100。
本发明实施例辅以说明本发明的技术方案,但实施例的内容并不局限于此,部分目标化合物实验结果如表3所示。
表3色胺酮7位或9位取代芳香硫醚衍生物对三种植物病原菌细菌的抑制活性
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测试结果为三次测定平均值。
上述实验活性数据表明,所测试的色胺酮7位或9位取代芳香硫醚衍生物对植物病原菌细菌均具有较好的抑制活性,该测试浓度下部分化合物的初筛抑制率优于阳性对照化合物叶枯唑和噻菌酮,可作为潜在的抑制植物细菌的候选先导化合物,具有较好的研究应用价值。
Claims (4)
1.一类色胺酮7位或9位取代芳香硫醚衍生物,其特征在于,该衍生物具有通式(Ⅰ)或(Ⅱ)所示的结构:
其中,R1为吡啶、嘧啶或三氟甲基取代吡啶;R2为氢或氟;R3为氢。
2.如权利要求1所述的一类色胺酮7位或9位取代芳香硫醚衍生物的制备方法,其特征在于:包括下述步骤:
3.一类组合物,其特征在于:含有权利要求1所述的衍生物或其盐类,以及农业上用的助剂或杀菌制剂。
4.如权利要求1所述的衍生物或权利要求3所述的组合物在农业病菌病害药物中的应用,所述的农业病菌为水稻白叶枯病菌(Xanthomonas oryzaepv.oryzae,Xoo)、柑橘溃疡病菌(Xanthomonascampestrispv.citri,Xac)、猕猴桃溃疡菌(seudomonassyringaepv.actinidiae,Psa)。
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103570726A (zh) * | 2013-07-15 | 2014-02-12 | 上海天慈生物谷生物工程有限公司 | N-烷基色胺酮衍生物及其制备方法和应用 |
CN109111405A (zh) * | 2018-10-22 | 2019-01-01 | 南开大学 | 一种芳香硫醚类化合物及其农药和医药用途 |
CN109956942A (zh) * | 2017-12-25 | 2019-07-02 | 上海翔锦生物科技有限公司 | 色胺酮类衍生物及其用途 |
CN113016814A (zh) * | 2019-12-24 | 2021-06-25 | 南开大学 | 色胺酮衍生物在治疗植物病毒病菌病中的应用 |
CN113024561A (zh) * | 2019-12-24 | 2021-06-25 | 南开大学 | 色胺酮衍生物及其制备和在防治植物病毒病菌病中的应用 |
CN113024562A (zh) * | 2019-12-24 | 2021-06-25 | 南开大学 | 含三氟甲硫基色胺酮衍生物及其制备和在防治植物病毒病菌病中的应用 |
CN114805353A (zh) * | 2022-01-11 | 2022-07-29 | 贵州大学 | 氮杂色胺酮类衍生物的合成及在防治植物病原菌细菌、真菌杀菌剂及抗植物病毒制剂的应用 |
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Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103570726A (zh) * | 2013-07-15 | 2014-02-12 | 上海天慈生物谷生物工程有限公司 | N-烷基色胺酮衍生物及其制备方法和应用 |
CN109956942A (zh) * | 2017-12-25 | 2019-07-02 | 上海翔锦生物科技有限公司 | 色胺酮类衍生物及其用途 |
CN109111405A (zh) * | 2018-10-22 | 2019-01-01 | 南开大学 | 一种芳香硫醚类化合物及其农药和医药用途 |
CN113016814A (zh) * | 2019-12-24 | 2021-06-25 | 南开大学 | 色胺酮衍生物在治疗植物病毒病菌病中的应用 |
CN113024561A (zh) * | 2019-12-24 | 2021-06-25 | 南开大学 | 色胺酮衍生物及其制备和在防治植物病毒病菌病中的应用 |
CN113024562A (zh) * | 2019-12-24 | 2021-06-25 | 南开大学 | 含三氟甲硫基色胺酮衍生物及其制备和在防治植物病毒病菌病中的应用 |
CN114805353A (zh) * | 2022-01-11 | 2022-07-29 | 贵州大学 | 氮杂色胺酮类衍生物的合成及在防治植物病原菌细菌、真菌杀菌剂及抗植物病毒制剂的应用 |
Non-Patent Citations (1)
Title |
---|
龚跃法主编.《有机化学 下册》.华东理工大学出版社,2010,(第1版),第168-169页. * |
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