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香豆素肟酯衍生物的合成及抑菌活性

袁含笑 张文广 刘函如 张云天 张彩霞 郭孜怡 高艳清 雷鹏 刘西莉

袁含笑, 张文广, 刘函如, 张云天, 张彩霞, 郭孜怡, 高艳清, 雷鹏, 刘西莉. 香豆素肟酯衍生物的合成及抑菌活性[J]. 农药学学报, 2022, 24(5): 1189-1195. doi: 10.16801/j.issn.1008-7303.2022.0078
引用本文: 袁含笑, 张文广, 刘函如, 张云天, 张彩霞, 郭孜怡, 高艳清, 雷鹏, 刘西莉. 香豆素肟酯衍生物的合成及抑菌活性[J]. 农药学学报, 2022, 24(5): 1189-1195. doi: 10.16801/j.issn.1008-7303.2022.0078
YUAN Hanxiao, ZHANG Wenguang, LIU Hanru, ZHANG Yuntian, ZHANG Caixia, GUO Ziyi, GAO Yanqing, LEI Peng, LIU Xili. Synthesis and antifungal activity of coumarin oxime esters[J]. Chinese Journal of Pesticide Science, 2022, 24(5): 1189-1195. doi: 10.16801/j.issn.1008-7303.2022.0078
Citation: YUAN Hanxiao, ZHANG Wenguang, LIU Hanru, ZHANG Yuntian, ZHANG Caixia, GUO Ziyi, GAO Yanqing, LEI Peng, LIU Xili. Synthesis and antifungal activity of coumarin oxime esters[J]. Chinese Journal of Pesticide Science, 2022, 24(5): 1189-1195. doi: 10.16801/j.issn.1008-7303.2022.0078

香豆素肟酯衍生物的合成及抑菌活性

doi: 10.16801/j.issn.1008-7303.2022.0078
基金项目: 陕西省技术创新引导专项 (2020QFY07-03);陕西省专项经费 (F2020221004);省级大学生创新创业训练计划项目 (S202210712432).
详细信息
    作者简介:

    袁含笑,153327297_yuan@nwafu.edu.cn

    通讯作者:

    雷鹏,peng.lei@nwafu.edu.cn

    刘西莉,seedling@nwafu.edu.cn

  • 中图分类号: TQ 450.11

Synthesis and antifungal activity of coumarin oxime esters

Funds: the Technology Innovation Guidance Special Fund of Shaanxi Province (2020QFY07-03); Special Fund of Shaanxi Province (F2020221004); Shaanxi Province Undergraduate Training Program for Innovation and Entrepreneurship (S202210712432)
  • 摘要: 为发现具有高抑菌活性的肟酯类化合物, 结合本课题组前期研究, 设计并合成了18个新型香豆素肟酯衍生物, 并对抑菌活性及构效关系进行了研究。离体生物活性测定结果表明, 目标化合物在50 μg/mL下对番茄灰霉病菌、苹果树腐烂病菌和水稻纹枯病菌均表现出一定的抑制活性, 其中化合物 4n 对番茄灰霉病菌和水稻纹枯病菌的EC50值分别为4.44 μg/mL和3.65 μg/mL,表现出比香豆素和肟菌酯更优或相似的活性。
  • 1  香豆素、蛇床子素、丁香菌酯和ZXL的化学结构式

    1.  Structural formulas of coumarin, osthol, coumoxystrobin and ZXL

    2  本研究组前期及本文中肟酯类化合物的结构式

    2.  Structural formulas of oxime esters in our previous work and this paper

    3  目标化合物的合成路线

    3.  Synthetic route of target compounds

    4  化合物4a的化学结构式

    4.  Structural formula of compound 4a

    表  1  目标化合物4a~4r在50 μg/mL下离体抑菌活性

    Table  1.   Antifungal activities in vitro of target compounds 4a-4r at 50 μg/mL

    化合物
    Compd.
    取代基
    R
    抑制率
    Inhibition rate/%
    苹果树腐烂
    病菌
    V. mali
    番茄灰霉
    病菌
    B. cinerea
    水稻纹枯
    病菌
    R. solani
    4a2-OMePh37.425.435.6
    4b3-OMePh0.42.723.5
    4c4-OMePh24.58.129.1
    4d2-ClPh8.919.226.1
    4e3-ClPh4.71.51.6
    4f4-ClPh3.516.52.6
    4g2-MePh21.013.532.0
    4h4-MePh16.316.916.3
    4i2-CF3Ph55.650.036.9
    4j3-CF3Ph9.313.53.6
    4k2-FPh21.413.830.7
    4l2-BrPh20.613.822.9
    4m3-BrPh0.410.41.6
    4nFuran-2-yl43.286.596.3
    4ot-Bu22.229.696.9
    4pn-Bu-4-Cl40.934.166.2
    4qn-Pr43.563.982.6
    4rThiophen-2-yl43.357.965.5
    香豆素
    coumarin
    39.145.276.3
    肟菌酯
    trifloxystrobin
    97.477.789.3
    下载: 导出CSV

    表  2  部分目标化合物对两种病原菌的EC50

    Table  2.   EC50 values of some target compounds against two pathogenic fungi

    病原菌
    Pathogenic fungi
    化合物
    Compound
    取代基
    R
    回归方程
    Regression equation
    决定系数
    R2
    EC50/(μg/mL)95% 置信限
    95% CL/(μg/mL)
    番茄灰霉病菌
    B. cinerea
    4n Furan-2-yl y = 0.889x − 0.576 0.957 4.44 3.10~5.90
    肟菌酯
    trifloxystrobin
    y = 0.975x − 0.955 0.978 9.54 7.42~12.33
    水稻纹枯病菌
    R. solani
    4n Furan-2-yl y = 1.270x − 0.714 0.935 3.65 1.83~5.65
    4o t-Bu y = 1.221x − 0.657 0.923 3.45 2.59~4.34
    4q n-Pr y = 1.202x − 1.230 0.962 10.55 8.59~13.08
    香豆素
    coumarin
    y = 1.056x − 1.202 0.981 13.75 10.89~17.91
    肟菌酯
    trifloxystrobin
    y = 0.959x − 0.634 0.939 4.58 3.31~5.56
    下载: 导出CSV
  • [1] SPARKS T C, HAHN D R, GARIZI N V. Natural products, their derivatives, mimics and synthetic equivalents: role in agrochemical discovery[J]. Pest Manag Sci, 2017, 73(4): 700-715. doi: 10.1002/ps.4458
    [2] VENUGOPALA K N, RASHMI V, ODHAV B. Review on natural coumarin lead compounds for their pharmacological activity[J]. Biomed Res Int, 2013: 963248.
    [3] HUANG J, LIANG P, XU J, et al. Qualitative and quantitative determination of coumarin using surface-enhanced Raman spectroscopy coupled with intelligent multivariate analysis[J]. RSC Adv, 2017, 7(77): 49097-49101. doi: 10.1039/C7RA09059E
    [4] VERHOEF T I, REDEKOP W K, DALY A K, et al. Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon[J]. Brit J Clin Pharmaco, 2014, 77(4): 626-641. doi: 10.1111/bcp.12220
    [5] EMAMI S, DADASHPOUR S. Current developments of coumarin-based anti-cancer agents in medicinal chemistry[J]. Eur J Med Chem, 2015, 102: 611-630. doi: 10.1016/j.ejmech.2015.08.033
    [6] FYLAKTAKIDOU K C, HADJIPAVLOU-LITINA D J, LITINAS K E, et al. Natural and synthetic coumarin derivatives with anti-inflammatory/antioxidant activities[J]. Curr Pharm Design, 2004, 10(30): 3813-3833. doi: 10.2174/1381612043382710
    [7] 杜康, 陈睿嘉, 李忠, 等. 香豆素型呋虫胺光控化合物的设计、合成、光学特性及杀虫活性[J]. 农药学学报, 2022, 24(1): 31-38. doi: 10.16801/j.issn.1008-7303.2021.0146

    DU K, CHEN R J, LI Z, et al. Design, synthesis, photophysical properties and insecticidal activities of coumarin compound for the photocontrolled release of dinotefuran[J]. Chin J Pestic Sci, 2022, 24(1): 31-38. doi: 10.16801/j.issn.1008-7303.2021.0146
    [8] 刘瑾林, 周红, 郭富友, 等. 香豆素类化合物的农药活性及东莨菪内酯杀螨作用机理研究进展[J]. 农药学学报, 2019, 21(5-6): 692-708.

    LIU J L, ZHOU H, GUO F Y, et al. Research advances in pesticidal activities of coumarin derivatives and acaricidal mechanism of scopoletin[J]. Chin J Pestic Sci, 2019, 21(5-6): 692-708.
    [9] 丁建芬, 刘莉, 夏梅, 等. 新型香豆素衍生物的设计、合成及除草活性研究[J]. 合成化学, 2021, 29(7): 577-583.

    DING J F, LIU L, XIA M, et al. Design, synthesis and herbicidal activity of novel coumarin derivatives[J]. Chin J Synth Chem, 2021, 29(7): 577-583.
    [10] 马伟虎, 程红刚, 杨璟, 等. 香豆素对灰葡萄孢霉菌抑菌作用机理初探[J]. 农药学学报, 2020, 22(5): 775-781.

    MA W H, CHENG H G, YANG J, et al. Preliminary study on the antifungal mechanism of coumarin on Botrytis cinerea[J]. Chin J Pestic Sci, 2020, 22(5): 775-781.
    [11] 石志琦, 沈寿国, 徐朗莱, 等. 蛇床子素对植物病原真菌抑制机制的初步研究[J]. 农药学学报, 2004, 6(4): 28-32. doi: 10.3321/j.issn:1008-7303.2004.04.006

    SHI Z Q, SHEN S G, XU L L, et al. Inhibition mechanism of osthole to plant fungus pathogens[J]. Chin J Pestic Sci, 2004, 6(4): 28-32. doi: 10.3321/j.issn:1008-7303.2004.04.006
    [12] 关爱莹, 刘长令, 李志念, 等. 杀菌剂丁香菌酯的创制经纬[J]. 农药, 2011, 50(2): 90-92. doi: 10.3969/j.issn.1006-0413.2011.02.004

    GUAN A Y, LIU C L, LI Z N, et al. The discovery of fungicide coumoxystrobin[J]. Agrochemicals, 2011, 50(2): 90-92. doi: 10.3969/j.issn.1006-0413.2011.02.004
    [13] 张学良, 魏艳, 韦能春, 等. 10种N-取代氨基香豆素的合成及生物活性[J]. 农药学学报, 2013, 15(1): 37-42. doi: 10.3969/j.issn.1008-7303.2013.01.05

    ZHANG X L, WEI Y, WEI N C, et al. Synthesis and bioactivity of 10 N-substituted amino coumarins[J]. Chin J Pestic Sci, 2013, 15(1): 37-42. doi: 10.3969/j.issn.1008-7303.2013.01.05
    [14] 昝宁宁, 万福贤, 王士春, 等. 含吡啶环的3-苯基-1-丙酮肟醚的合成及生物活性[J]. 有机化学, 2017, 37: 1537-1541. doi: 10.6023/cjoc201701009

    ZAN N N, WAN F X, WANG S C, et al. Synthesis and biological activity of novel 3-phenylpropan-1-one oxime ethers containing pyridine moiety[J]. Chin J Org Chem, 2017, 37: 1537-1541. doi: 10.6023/cjoc201701009
    [15] 沈安泽, 胡恩畅, 刘函如, 等. 含肟酯的吡唑衍生物的合成及其抑菌活性[J]. 农药学学报, 2021, 23(1): 69-75. doi: 10.16801/j.issn.1008-7303.2021.0005

    SHEN A Z, HU E C, LIU H R, et al. Synthesis and antifungal activities of pyrazole derivatives containing oxime esters[J]. Chin J Pestic Sci, 2021, 23(1): 69-75. doi: 10.16801/j.issn.1008-7303.2021.0005
    [16] 张兴甲, 魏志敏, 王宇佳, 等. 3-二氟甲基-1-甲基吡唑-4-羧酸肟酯衍生物的合成及抑菌活性[J]. 农药学学报, 2022, 24(1): 59-65. doi: 10.16801/j.issn.1008-7303.2021.0140

    ZHANG X J, WEI Z M, WANG Y J, et al. Synthesis and antifungal activity of 3-(difluoromethyl)-1-methyl pyrazole-4-carboxylic oxime esters[J]. Chin J Pestic Sci, 2022, 24(1): 59-65. doi: 10.16801/j.issn.1008-7303.2021.0140
    [17] WANG Y J, MU Y L, HU X T, et al. Indole/tetrahydroquinoline as renewable natural resource-inspired scaffolds in the devising and preparation of potential fungicide candidates[J]. J Agric Food Chem, 2022, 70(15): 4582-4590. doi: 10.1021/acs.jafc.1c07879
    [18] LEE S K, CHOI M G, CHANG S-K. Signaling of chloramine: a fluorescent probe for trichloroisocyanuric acid based on deoximation of a coumarin oxime[J]. Tetrahedron Lett, 2014, 55(51): 7047-7050. doi: 10.1016/j.tetlet.2014.10.132
    [19] HU Y G, GAO Y Q, WANG Y J, et al. Non-food bioactive products: diversified invention of 1,2,4-oxadiazole-containing amide derivatives for novel fungicidal candidate discovery[J]. Ind Crop Prod, 2022, 184: 115087. doi: 10.1016/j.indcrop.2022.115087
    [20] 陈年春. 农药生物测定技术[M]. 北京: 北京农业大学出版社, 1991: 161-162.

    Chen N C. Bioassay of Pesticides[M]. Beijing: Beijing Agricultural University Press, 1991: 161-162.
    [21] CARTA F, VULLO D, MARESCA A, et al. New chemotypes acting as isozyme-selective carbonic anhydrase inhibitors with low affinity for the offtarget cytosolic isoform II[J]. Bioorg Med Chem Lett, 2012, 22(6): 2182-2185. doi: 10.1016/j.bmcl.2012.01.129
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出版历程
  • 收稿日期:  2022-07-06
  • 录用日期:  2022-08-11
  • 网络出版日期:  2022-08-18
  • 刊出日期:  2022-10-10

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