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含稠杂环结构的螺环丁烯内酯类化合物的合成及杀菌活性

李益豪 许磊川 张倩 马好运 安鑫鲲 王明安

李益豪, 许磊川, 张倩, 马好运, 安鑫鲲, 王明安. 含稠杂环结构的螺环丁烯内酯类化合物的合成及杀菌活性[J]. 农药学学报, 2022, 24(5): 1152-1161. doi: 10.16801/j.issn.1008-7303.2022.0077
引用本文: 李益豪, 许磊川, 张倩, 马好运, 安鑫鲲, 王明安. 含稠杂环结构的螺环丁烯内酯类化合物的合成及杀菌活性[J]. 农药学学报, 2022, 24(5): 1152-1161. doi: 10.16801/j.issn.1008-7303.2022.0077
LI Yihao, XU Leichuan, ZHANG Qian, MA Haoyun, AN Xinkun, WANG Mingan. Synthesis and fungicidal activities of spirocyclic butenolide derivatives containing fused heterocyclic moiety[J]. Chinese Journal of Pesticide Science, 2022, 24(5): 1152-1161. doi: 10.16801/j.issn.1008-7303.2022.0077
Citation: LI Yihao, XU Leichuan, ZHANG Qian, MA Haoyun, AN Xinkun, WANG Mingan. Synthesis and fungicidal activities of spirocyclic butenolide derivatives containing fused heterocyclic moiety[J]. Chinese Journal of Pesticide Science, 2022, 24(5): 1152-1161. doi: 10.16801/j.issn.1008-7303.2022.0077

含稠杂环结构的螺环丁烯内酯类化合物的合成及杀菌活性

doi: 10.16801/j.issn.1008-7303.2022.0077
基金项目: 国家自然科学基金(21772229).
详细信息
    作者简介:

    李益豪,2353180713@qq.com

    通讯作者:

    王明安,wangma@cau.edu.cn

  • 中图分类号: O626;TQ450.11

Synthesis and fungicidal activities of spirocyclic butenolide derivatives containing fused heterocyclic moiety

Funds: the National Natural Science Foundation of China (21772229).
  • 摘要: 为了发现更高杀菌活性的螺环丁烯内酯类化合物并分析该类化合物的构效关系,设计并合成了一系列未见文献报道的含咪唑并噻唑、咪唑并噻嗪和咪唑并噻嗪酮等稠杂环结构的螺环丁烯内酯类化合物,其结构通过核磁共振氢谱 (1H NMR)、碳谱 (13C NMR)及高分辨质谱 (HRMS)确证。离体杀菌活性测试结果表明,化合物 5f6f 对油菜菌核病菌的EC50值分别为33.2和29.8 mg/L,优于对照药剂咪唑菌酮(46.8 mg/L),化合物 7b7e 对辣椒疫霉的EC50值分别为45.8和43.5 mg/L,优于咪唑菌酮(50.7 mg/L),与先导化合物相比,其杀菌活性高于2-甲硫基衍生物,低于2-芳氨基衍生物,表明稠杂环的引入可以提高化合物的杀菌活性,而结构中的NH片段对杀菌活性具有关键作用。
  • 1  典型的5,5-螺环丁烯内酯类天然产物和杀虫剂的化学结构

    1.  The structures of typical 5,5- spirocyclic butenolides natural products and insecticides

    2  含稠杂环结构螺环丁烯内酯化合物的设计策略

    2.  The design strategy of spirocyclic butenolides containing fused heterocycles

    3  目标化合物的合成路线

    3.  Synthetic route of target compounds

    图  1  几个目标化合物 1H NMR的局部特征峰

    Figure  1.  The local characteristic 1H NMR peaks of several target compounds

    表  1  目标化合物5a~5f、6a~6f 和7a~7f的离体杀菌活性(抑制率/%, 50 mg/L)

    Table  1.   The in vitro fungicidal activity of compounds 5a-5f, 6a-6f and 7a-7f (inhibition rate/%, 50 mg/L)

    化合物
    Compd.
    番茄灰霉病菌
    B. cinerea
    辣椒疫霉
    P. capsici
    棉花立枯丝核菌
    R. solani
    小麦赤霉病菌
    F. graminearum
    油菜菌核病菌
    S. sclerotiorum
    5a0.05.7 ± 1.216.3 ± 1.24.5 ± 1.911.3 ± 2.1
    5b10.3 ± 2.161.3 ± 4.219.8 ± 2.037.5 ± 4.236.3 ± 4.9
    5c44.6 ± 1.761.4 ± 1.99.8 ± 1.133.9 ± 2.824.5 ± 1.9
    5d2.4 ± 0.856.0 ± 2.324.8 ± 3.540.2 ± 2.934.8 ± 2.9
    5e23.2 ± 1.557.5 ± 1.931.5 ± 4.049.4 ± 4.140.5 ± 1.7
    5f11.2 ± 2.339.5 ± 2.337.4 ± 2.84.5.4 ± 3.268.7 ± 2.0
    6a43.0 ± 3.712.1 ± 3.10.010.2 ± 1.60.4 ± 0.1
    6b0.055.4 ± 3.49.4 ± 2.133.4 ± 3.923.2 ± 4.1
    6c35.2 ± 4.154.3 ± 1.48.3 ± 1.832.7 ± 1.124.9 ± 1.5
    6d11.3 ± 2.458.8 ± 1.926.5 ± 4.543.3 ± 0.833.2 ± 1.7
    6e15.7 ± 1.659.3 ± 4.129.8 ± 2.143.7 ± 0.925.9 ± 3.0
    6f7.9 ± 2.023.6 ± 2.032.4 ± 4.540.5 ± 4.168.3 ± 2.4
    7a12.6 ± 1.821.9 ± 1.727.0 ± 1.915.8 ± 1.64.4 ± 1.6
    7b15.4 ± 1.871.5 ± 2.90.04.6 ± 0.56.0 ± 2.0
    7c44.9 ± 2.565.0 ± 2.818.8 ± 3.125.6 ± 4.72.6 ± 1.8
    7d14.6 ± 2.762.5 ± 3.224.6 ± 1.640.2 ± 3.423.6 ± 1.9
    7e22.2 ± 3.472.7 ± 1.915.4 ± 2.929.7 ± 1.910.3 ± 2.3
    7f5.0 ± 1.140.1 ± 3.50.014.7 ± 2.025.6 ± 2.9
    多菌灵 carbendazim11.9 ± 2.05.8 ± 2.6100.0100.011.3 ± 3.0
    咪唑菌酮 fenamidone33.6 ± 2.853.1 ± 1.882.6 ± 2.844.4 ± 3.460.4 ± 2.0
    注:表中数据为3个重复的平均值 ± 标准差(SD)。Note: Values in table are the mean ± standard deviation (SD) of three replicates.
    下载: 导出CSV

    表  2  部分化合物对供试病原真菌的EC50

    Table  2.   EC50 values of some compounds against tested pathogenic fungi

    化合物
    Compd.
    病原真菌
    Pathogenic fungi
    EC50/(mg/L)95% CL/(mg/L)回归方程
    Regression equation
    决定系数
    R2
    7b辣椒疫霉 P. capsici45.838.7~53.9 y = 1.67 x + 2.220.987
    7c辣椒疫霉 P. capsici53.647.3~61.9 y = 1.41 x + 2.560.972
    7e辣椒疫霉 P. capsici43.535.6~51.2 y = 1.49 x + 2.550.933
    咪唑菌酮 fenamidone辣椒疫霉 P. capsici50.742.8~59.6 y = 1.41 x + 2.590.971
    5f油菜菌核病菌 S. sclerotiorum33.227.6~39.8 y = 1.77 x + 2.290.993
    6f油菜菌核病菌 S. sclerotiorum29.820.1~39.4 y = 1.84 x + 2.290.985
    咪唑菌酮 fenamidone油菜菌核病菌 S. sclerotiorum46.835.1~68.4 y = 1.52 x + 2.460.961
    下载: 导出CSV
  • [1] SCHREIBER S L. Target-oriented and diversity-oriented organic synthesis in drug discovery[J]. Science, 2000, 287(5460): 1964-1969. doi: 10.1126/science.287.5460.1964
    [2] GARCIA-CASTRO M, ZIMMERMANN S, SANKAR M G, et al. Scaffold diversity synthesis and its application in probeand drug discovery[J]. Angew Chem Int Ed Engl, 2016, 55(27): 7586-7605. doi: 10.1002/anie.201508818
    [3] PHAM T T, CHEN X, SÖHNEL T, et al. Haber-independent, diversity-oriented synthesis of nitrogen compounds from biorenewable chitin[J]. Green Chem, 2020, 22(6): 1978-1984. doi: 10.1039/D0GC00208A
    [4] HUANG Y Q, GUO Z L, SONG H J, et al. Design, synthesis, and biological activity of β-carboline analogues containing hydantoin, thiohydantoin, and urea moieties[J]. J Agric Food Chem, 2018, 66(31): 8253-8261. doi: 10.1021/acs.jafc.8b03087
    [5] MA D, YIN Y, CHEN Y L, et al. Design, step-economical diversity-oriented synthesis of an N-heterocyclic library containing a pyrimidine moiety: discovery of novel potential herbicidal agents[J]. RSC Adv, 2021, 11(25): 15380-15386. doi: 10.1039/D1RA02663A
    [6] MURAKAMI T, MORIKAWA Y, HASHIMOTO M, et al. Lambertellols A and B, novel 3,4-dihydronaphthalen-1(2H)-ones with spiro-butenolide produced by Lambertella sp. 1346[J]. Org Lett, 2004, 6(2): 157-160. doi: 10.1021/ol035889d
    [7] LIU M T, LIN S, GAN M L, et al. Yaoshanenolides A and B: new spirolactones from the bark of Machilus yaoshansis[J]. Org Lett, 2012, 14(4): 1004-1007. doi: 10.1021/ol300130s
    [8] LEHMANN J, RICHERS J, PÖTHIG A, et al. Synthesis of ramariolide natural products and discovery of their targets in mycobacteria[J]. Chem Commun, 2017, 53(1): 107-110. doi: 10.1039/C6CC08365J
    [9] LIU T X. Toxicity and efficacy of spiromesifen, a tetronic acid insecticide, against sweetpotato whitefly (Homoptera: Aleyrodidae) on melons and collards[J]. Crop Protection, 2004, 23(6): 505-513. doi: 10.1016/j.cropro.2003.10.006
    [10] NAUEN R, BRETSCHNEIDER T, ELBERT A, et al. Spirodiclofen and spiromesifen[J]. Pestic Outlook, 2003, 14(6): 243-246. doi: 10.1039/b314855f
    [11] MUEHLEBACH M, BUCHHOLZ A, ZAMBACH W, et al. Spiro N-methoxy piperidine ring containing aryldiones for the control of sucking insects and mites: discovery of spiropidion[J]. Pest Manag Sci, 2020, 76(10): 3440-3450. doi: 10.1002/ps.5743
    [12] JEANMART S, EDMUNDS A J F, LAMBERT C, et al. Synthetic approaches to the 2015-2018 new agrochemicals[J]. Bioorg Med Chem, 2021, 39: 116162. doi: 10.1016/j.bmc.2021.116162
    [13] TANG B, YANG M Y, ZHAO Y, et al. Discovery of 5-(5,5-dimethylbutenolide-3-ethylidene)-2-amino-imidazolinone derivatives as fungicidal agents[J]. Molecules, 2015, 20(8): 13470-13752.
    [14] TANG B, GUAN A Y, ZHAO Y, et al. Synthesis and fungicidal activity of (E)-5-[1-(2-oxo-1-oxaspiro[4,5]dec/non-3-en-3-yl)ethylidene]-2-aminoimidazolin-4-one derivatives[J]. Chin J Chem, 2017, 35(7): 1133-1140. doi: 10.1002/cjoc.201600794
    [15] ZHAO Y, TANG B, GUAN A Y, et al. Synthesis and fungicidal activity of (E)-5-[1-(4-phenyl-2-oxo-1-oxaspiro[4.5]dec-3-en-3-yl)ethylidene]-2-aminoimidazolin-4-one derivatives[J]. Synthesis, 2017, 49(20): 4663-4669. doi: 10.1055/s-0036-1588463
    [16] ZHAO Y, LIU X L, WANG W W, et al. Cs2CO3-promoted C3-alkylation of 4-((2,2-difluoro ethyl)amino)-5,5-disubsitutedfuran-2(5H)-ones with heteroarylmethyl chlorides[J]. Synthesis, 2018, 50(20): 4055-4062. doi: 10.1055/s-0037-1609548
    [17] 关爱莹, 赵宇, 王卫伟, 等. 3-乙酰基-4-苯基-1-氧代螺[4,5]癸-3-烯-2-酮类衍生物的合成及杀菌活性[J], 有机化学, 2018, 38(10): 2767-2774.

    GUAN A Y, ZHAO Y, WANG W W, et al. Synthesis and fungicidal activity of 3-acetyl-4-phenyl-1-oxaspiro [4,5]dec-3-en-2-one derivatives[J]. Chin J Org Chem, 2018, 38(10): 2767-2774.
    [18] 赵宇, 关爱莹, 李婉祯, 等. 新型特窗酸肼基衍生物的合成、杀菌及杀虫活性[J], 有机化学, 2019, 39(5): 1344-1353.

    ZHAO Y, GUAN A Y, LI W Z, et al. Synthesis, fungicidal and insecticidal activity of novel tetronic acid hydrazinyl derivatives[J]. Chin J Org Chem, 2019, 39(5): 1344-1353.
    [19] 耿瑞, 赵宇, 李益豪, 等. 含叔醇结构的新型吡唑-4-甲酰胺类化合物的合成及杀菌活性[J], 有机化学, 2019, 39(12): 3574-3582.

    GENG R, ZHAO Y, LI Y H, et al. Synthesis and fungicidal activity of novel pyrazole-4-carboxamide compounds containing tertiary alcohol moiety[J]. Chin J Org Chem, 2019, 39(12): 3574-3582.
    [20] 赵宇, 王卫伟, 刘鑫磊, 等. 无催化剂条件下4-羟基烷基-2-炔酸乙酯与N-杂环芳基甲基-N-2, 2-二氟乙基-1-胺的串联反应[J]. 有机化学, 2020, 40(3): 694-703. doi: 10.6023/cjoc201909009

    ZHAO Y, WANG W W, LIU X L, et al. Catalyst-free domino reaction of ethyl 4-hydroxyalkyl-2-ynoate with N-heteroarylmethyl-N-2,2-difluoroethan-1-amine[J]. Chin J Org Chem, 2020, 40(3): 694-703. doi: 10.6023/cjoc201909009
    [21] 赵宇, 刘鑫磊, 李益豪, 等. (E)-3-(1-亚胺基乙基)-5,5-二取代-4-甲氨基呋喃-2(5H)-酮的合成及其意外的杀虫活性[J]. 有机化学, 2020, 40(8): 2547-2554. doi: 10.6023/cjoc202004050

    ZHAO Y, LIU X L, LI Y H, et al. Synthesis and unexpected insecticidal activity of (E)-3-(1-iminoethyl)-5,5-disubstituted-4-(methylamino)furan-2(5H)-one[J]. Chin J Org Chem, 2020, 40(8): 2547-2554. doi: 10.6023/cjoc202004050
    [22] 张倩, 李益豪, 许磊川, 等. 新型含肟醚结构丁烯内酯类化合物的合成及杀菌活性[J]. 有机化学, 2022, 42(8): 2438-2448.

    ZHAO Q, LI Y H, XU L C, et al. Synthesis and fungicidal activity of novel butenolide compounds containing oxime ether moiety[J]. Chin J Org Chem, 2022, 42(8): 2438-2448.
    [23] 李益豪, 赵宇, 许磊川, 等. 3-苄基-5-(1-(2-氧代-1-氧杂螺[4,5]癸-3-烯-3-基) 亚乙基)-2-氨基咪唑啉-4-酮类化合物的合成及杀菌活性[J]. 农药学学报, 2021, 23(6): 1097-1107.

    LI Y H, ZHAO Y, XU L C, et al. Synthesis and fungicidal activity of 3-benzyl-5-(1-(2-oxo-1-oxaspiro[4,5]dec-3-en-3-yl) ethylidene)-2-aminoimidazolin-4-one derivatives[J]. Chin J Pestic Sci, 2021, 23(6): 1097-1107.
    [24] SHIVAKUMAR S B, BASAVARAJU Y B, UMESHA B, et al. Synthesis and evaluation of antimitotic activity of new tetralone acid analogues of podophyllotoxin[J]. Eur J Chem, 2014, 5(3): 424-429. doi: 10.5155/eurjchem.5.3.424-429.1020
    [25] JANG D O, MOON K S, CHO D H, et al. Highly selective catalytic Friedel-​Crafts acylation and sulfonylation of activated aromatic compounds using indium metal[J]. Tetrahedron Lett, 2006, 47(34): 6063-6066. doi: 10.1016/j.tetlet.2006.06.099
    [26] KUROSU M, BISWAS K, NARAYANASAMY P, et al. Acid- and base-stable esters: a new protecting group for carboxylic acids[J]. Synthesis, 2007, 16: 2513-2516.
    [27] ZHOU L, GEVORGYAN V. Double duty for cyanogen bromide in a cascade synthesis of cyanoepoxides[J]. Angew Chem Int Ed Engl, 2011, 50(12): 2808-2810. doi: 10.1002/anie.201006966
    [28] HIRAYAMA T, UEDA S, OKADA T, et al. Facile one-​pot synthesis of [1,​2,​3]​triazolo[1,5-​a]​pyridines from 2-​acylpyridines by copper(II)​-catalyzed oxidative N−N bond formation[J]. Chemistry-Eur J, 2014, 20(14): 4156-4162. doi: 10.1002/chem.201302997
    [29] MAGD EL-DIN A A, ELSHARABASY S A, HASSAN A Y. Reaction of 5-arylidene-2-thiohydantoins with halogenated compounds and anthranilic acid[J]. Phosphorus, Sulfur, and Silicon, 2006, 181: 53-67. doi: 10.1080/104265090968677
    [30] YUAN J Z, FU B Q, DING M W, et al. New facile synthesis of 3,5-dihydro-6H-imidazo[1,2-b]-1,2,4 -triazol-6-ones by an iminophosphorane-mediated annulation[J]. Eur J Org Chem, 2006, 18: 4170-4176.
    [31] ABU-HASHEM A A, AL-HUSSAIN S A, ZAKI M E A. Synthesis of novel benzodifuranyl; 1,3,5-triazines; 1,3,5-oxadiazepines; and thiazolopyrimidines derived from visnaginone and khellinone as anti-inflammatory and analgesic agents[J]. Molecules, 2020, 25(1): 220-244. doi: 10.3390/molecules25010220
    [32] 农药室内生物测定实验准则 杀菌剂第 2 部分: 抑制病原真菌菌丝生长实验平皿法: NY/T1156.2—2006[S]. 北京: 中国农业出版社, 2006.

    Pesticides guidelines for laboratory bioactivity test. Part 2: petri plate test for determining fungicide inhibition of mycelial growth: NY/T1156. 2—2006[S]. Beijing: China Agricultural Press, 2006.
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  • 收稿日期:  2022-07-08
  • 录用日期:  2022-08-12
  • 网络出版日期:  2022-08-16
  • 刊出日期:  2022-10-10

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