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喹唑啉酮肟醚衍生物的设计、合成、杀菌活性及其与琥珀酸脱氢酶受体的结合模式

王金玲 李忠

王金玲, 李忠. 喹唑啉酮肟醚衍生物的设计、合成、杀菌活性及其与琥珀酸脱氢酶受体的结合模式[J]. 农药学学报, 2022, 24(5): 1162-1170. doi: 10.16801/j.issn.1008-7303.2022.0067
引用本文: 王金玲, 李忠. 喹唑啉酮肟醚衍生物的设计、合成、杀菌活性及其与琥珀酸脱氢酶受体的结合模式[J]. 农药学学报, 2022, 24(5): 1162-1170. doi: 10.16801/j.issn.1008-7303.2022.0067
WANG Jinling, LI Zhong. Design, synthesis, antifungal activities and binding mode with succinate dehydrogenase receptor of quinazolinone oxime ether derivatives[J]. Chinese Journal of Pesticide Science, 2022, 24(5): 1162-1170. doi: 10.16801/j.issn.1008-7303.2022.0067
Citation: WANG Jinling, LI Zhong. Design, synthesis, antifungal activities and binding mode with succinate dehydrogenase receptor of quinazolinone oxime ether derivatives[J]. Chinese Journal of Pesticide Science, 2022, 24(5): 1162-1170. doi: 10.16801/j.issn.1008-7303.2022.0067

喹唑啉酮肟醚衍生物的设计、合成、杀菌活性及其与琥珀酸脱氢酶受体的结合模式

doi: 10.16801/j.issn.1008-7303.2022.0067
基金项目: 国家重点研发计划 (2017YFD0200505)
详细信息
    作者简介:

    王金玲,13598081737@163.com

    通讯作者:

    李忠,lizhong@ecust.edu.cn

  • 中图分类号: O624.6;O623.626;TQ450.11

Design, synthesis, antifungal activities and binding mode with succinate dehydrogenase receptor of quinazolinone oxime ether derivatives

Funds: the National Key Research and Development Program of China (2017YFD0200505).
  • 摘要: 为寻找高活性杀菌化合物,以氟吡菌酰胺为对照,在前期发现的新型硝基甲基喹唑啉酮骨架的基础上,通过中间体衍生化法和活性亚结构拼接等手段,设计、合成了25个未见文献报道的喹唑啉酮肟醚衍生物,所有化合物的结构均通过核磁共振氢谱 (1H NMR)、碳谱 (13C NMR) 及高分辨质谱 (HR-EI-MS) 确证。活体杀菌活性测试表明,目标化合物 A19A25 在500 mg/L下对小麦赤霉病菌Fusarium graminearum的防效分别为43.74%和42.46%,活性远低于氟吡菌酰胺。初步分析,其理化性质以及其与琥珀酸脱氢酶 (SDH) 受体结合模式方面的差异可能是导致这些化合物活性比氟吡菌酰胺低的主要原因。
  • 1  含有肟醚结构的代表性农药[9]

    1.  Representative pesticides containing oxime ether structures[9]

    2  目标化合物的分子设计示意图

    2.  Design strategy of the target compounds

    3  目标化合物的合成路线

    3.  Synthetic route of target compounds

    图  1  氟吡菌酰胺(淡红色)及A19 (绿色)与SDH受体的结合模式

    Figure  1.  Binding mode of fluopyram (light red) and A19 (green) with SDH receptor

    表  1  关键中间体7的合成条件筛选

    Table  1.   Screening of synthetic conditions for key intermediate 7

    编号
    Number
    反应试剂
    Reagents
    温度
    Temperature/℃
    溶剂
    Solvent
    收率
    Yield/%
    1 Mg(ClO4)2/i-Pr2NEt r.t. CH3CN 80
    2 Mg(ClO4)2/Et3N r.t.~80 CH3CN -
    3 LiBF4/i-Pr2NEt r.t. CH3CN 75
    4 CS2/TBD 0~r.t. DCM 75
    5 NaNO2 r.t. DMSO/H2O 68
    6 n-BuLi/Me3SiSiMe3 0~ r.t. THF 71
    7 SnCl2 r.t. THF 85
    8 SnCl2 r.t. EtOH 80
    9 SnCl2 r.t. DCM 54
    10 AlCl3 r.t. THF 50
    下载: 导出CSV

    表  2  目标化合物的理化性质以及活体杀菌活性

    Table  2.   The physiochemical properties and in vivo antifungal activities of target compounds

    化合物
    Compd.
    理化性质
    Physiochemical properties
    防治效果
    Control efficacy/%
    (500 mg/L)
    logP logS pKa TPSA/Å2 小麦赤霉病菌
    Fusarium graminearum
    A1 1.65 −2.87 1.22 63.05 14.46
    A2 1.14 −2.59 1.22 63.05 11.11
    A3 2.48 −3.65 1.22 63.05 17.97
    A4 1.65 −3.21 1.22 63.05 16.67
    A5 1.00 −3.58 1.22 63.05 23.70
    A6 0.95 −3.72 1.22 63.05 31.85
    A7 1.93 −3.71 1.22 63.05 8.89
    A8 2.53 −4.25 1.22 63.05 24.65
    A9 2.18 −4.01 1.22 72.28 32.59
    A10 2.52 −4.24 1.22 63.05 22.22
    A11 2.53 −4.25 1.22 63.05 32.56
    A12 2.23 −4.35 1.22 63.05 −5.37
    A13 2.35 −4.32 1.22 63.05 8.15
    A14 2.36 −4.39 1.22 63.05 32.59
    A15 2.78 −4.79 1.22 63.05 34.07
    A16 2.90 −4.41 1.22 63.05 12.59
    A17 2.89 −4.42 1.22 63.05 −6.67
    A18 3.06 −4.66 1.22 63.05 15.56
    A19 3.51 −4.94 1.22 63.05 43.74
    A20 4.00 −5.23 1.22 63.05 12.59
    A21 2.87 −4.50 1.22 63.05 −2.96
    A22 3.30 −4.93 1.22 63.05 37.78
    A23 2.29 −4.21 1.22 63.05 12.59
    A24 3.27 −5.11 1.22 63.05 12.59
    A25 2.20 −3.87 1.33 75.94 42.46
    氟吡菌酰胺 fluopyram 3.87 −5.13 1.72 41.99 100.00
    CK 0.00
    下载: 导出CSV
  • [1] HAMEED A, Al-RASHIDA M, UROOS M, et al. Quinazoline and quinazolinone as important medicinal scaffolds: a comparative patent review (2011-2016)[J/OL]. Expert Opin Ther Pat, 2018, 28: 281-297 [2022-05-01]. https://www.tandfonline.com/doi/abs/10.1080/13543776.2018.1432596?journalCode=ietp20.
    [2] SHANG X F, SUSAN L M N, LIN Y Q, et al. Biologically active quinoline and quinazoline alkaloids part I [J/OL]. Med Res Rev, 2018, 38: 775-82 [2022-05-01]. https://onlinelibrary.wiley.com/doi/full/10.1002/med.21466.
    [3] HAO Y N, YU M, WANG K H, et al. Discovery of glyantrypine-family alkaloids as novel antiviral and antiphytopathogenic-fungus agents[J]. Pest Manage Sci, 2022, 78(3): 982-990. doi: 10.1002/ps.6709
    [4] PENG J W, YIN X D, LI H, et al. Design, Synthesis, and structure-activity relationship of quinazolinone derivatives as potential fungicides[J]. J Agric Food Chem, 2021, 69(16): 4604-4614. doi: 10.1021/acs.jafc.0c05475
    [5] ZhOU Y Y, FENG Q, DI F J, et al. Synthesis and insecticidal activities of 2,3-dihydroquinazolin-4(1H)-one derivatives targeting calcium channel[J]. Bioorg Med Chem, 2013, 21(17): 4968-4975. doi: 10.1016/j.bmc.2013.06.060
    [6] QU R Y, NAN J X, YAN Y C, et al. Structure-guided discovery of silicon-containing subnanomolar inhibitor of hydroxyphenylpyruvate dioxygenase as a potential herbicide[J]. J Agric Food Chem, 2021, 69(1): 459-473. doi: 10.1021/acs.jafc.0c03844
    [7] MA J, LI P, LI X Y, et al. Synthesis and antiviral bioactivity of novel 3-((2-((1E,4E)-3-oxo-5-arylpenta-1,4-dien-1-yl) phenoxy) methyl)-4(3H)-quinazolinone derivatives[J]. J Agric Food Chem, 2014, 62(36): 8928-8934. doi: 10.1021/jf502162y
    [8] HAO Y N, GUO J C, WANG Z W, et al. Discovery of tryptanthrins as novel antiviral and anti-phytopathogenic-fungus agents[J]. J Agric Food Chem, 2020, 68(20): 5586-5595. doi: 10.1021/acs.jafc.0c02101
    [9] 范磊, 崔建国, 韦英亮, 等. 具有生物活性的肟醚类化合物的研究进展[J]. 现代农药, 2008, 7(2): 6-11. doi: 10.3969/j.issn.1671-5284.2008.02.002

    FAN L, CUI J G, WEI Y L, et al. Recent advance of oxime-ethers and biological activity[J]. Modern AgroChem, 2008, 7(2): 6-11. doi: 10.3969/j.issn.1671-5284.2008.02.002
    [10] WANG M L, DU Y, LING C, et al. Design, synthesis and antifungal/anti-oomycete activity of pyrazolyl oxime ethers as novel potential succinate dehydrogenase inhibitors[J]. Pest Manage Sci, 2021, 77: 3910-3920. doi: 10.1002/ps.6418
    [11] BO L, YU L N. Comprehensive overview of carboxamide derivatives as succinate dehydrogenase inhibitors[J]. J Agric Food Chem, 2022, 70(4): 957-975. doi: 10.1021/acs.jafc.1c06654
    [12] ANDERSCH W. Use of fluopyram and compositions comprising fluopyram for controlling nematodes in nematode-resistant crops. WO2012038476[P/OL]. 2012-03-29[2022-05-08]. http://www.google.com/patents/WO2012038476.
    [13] ZHU F J, TIAN X, SHAO X S. Direct amidation of aniline derivatives with 1,1-dichloro-2-nitroethene in water[J]. Tetrahedron Lett, 2015, 56(43): 5945-5949. doi: 10.1016/j.tetlet.2015.09.048
    [14] MANDAPATI B R, KESAVAN P, RAMASAMY A. Visible-light induced copper(i)-catalyzed oxidative cyclization of o-aminobenzamides with methanol and ethanol via HAT[J]. Org Biomol Chem, 2020, 18: 9601-9605. doi: 10.1039/D0OB02234A
    [15] CHANG X S, SUN D J, SHI D F, et al. Design, synthesis, and biological evaluation of quinazolin-4(3H)-one derivatives co-targeting poly (ADP-ribose) polymerase-1 and bromodomain containing protein 4 for breast cancer therapy[J]. APSB, 2021, 11(1): 156-180.
    [16] ZHU F J, SONG R J, SHEN L, et al. In-water synthesis of quinazolinones from 1,1-dichloro-2-nitroethene and anthranilamides[J]. Synlett, 2016, 27(14): 2167-2170. doi: 10.1055/s-0035-1561640
    [17] TRONG D T, NGOC B P, GREGORY F, et al. Bromotyrosine alkaloids from the Australian marine sponge Pseudoceratina verrucose[J/OL]. J Nat Prod, 2013, 76, (4): 516-523 [2022-05-08]. https://www.mdpi.com/1660-3397/16/12/463.
    [18] GUAN A Y, LIU C L, CHEN W, et al. Design, synthesis, and structure-activity relationship of new pyrimidinamine derivatives containing an aryloxy pyridine moiety[J]. J Agric Food Chem, 2017, 65(6): 1272-1280. doi: 10.1021/acs.jafc.6b05580
    [19] 农药室内生物测定试验准则 杀菌剂 第4部分: 防治小麦白粉病试验 盆栽法: NY/T 1156.4—2006[S]. 北京: 中国农业出版社, 2006.

    Pesticides guidelines for laboratory bioactivity tests. Part 4. Potted plant test for fungicide control of powdery mildew on wheat: NY/T 1156.4—2006 [S]. Beijing: China Agriculture Press, 2006.
    [20] 农药田间药效试验准则 (一): GB/T 17980.23—2000[S]. 北京: 中国标准出版社, 2000.

    Pesticide guidelines for the field efficacy trials (Ⅰ): GB/T 17980.23—2000 [S]. Beijing: Standards Press of China, 2000.
    [21] 农药田间药效试验准则 (二): GB/T 17980—2000[S]. 北京: 中国标准出版社, 2000.

    Pesficide: guidelines for the field efficacy trials (II): GB/T 17980—2000[S]. Beijing: Standards Press of China, 2000.
    [22] 刘斌, 俞飞, 姚建华, 等. 杀菌剂、除草剂和杀虫剂的先导筛选规则[J]. 农药学学报, 2007, 9(3): 220-228. doi: 10.3321/j.issn:1008-7303.2007.03.004

    LIU B, YU F, YAO J H, et al. Screening rules of lead compounds of herbicide, fungicide and insecticide[J]. Chin J Pestic Sci, 2007, 9(3): 220-228. doi: 10.3321/j.issn:1008-7303.2007.03.004
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出版历程
  • 收稿日期:  2022-05-10
  • 录用日期:  2022-06-27
  • 网络出版日期:  2022-07-19
  • 刊出日期:  2022-10-10

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