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氘标记稻瘟酯的合成及其杀菌活性

范鑫鑫 韩敏晖 丁宇轩 张学博 李恒朝 安杰

范鑫鑫, 韩敏晖, 丁宇轩, 张学博, 李恒朝, 安杰. 氘标记稻瘟酯的合成及其杀菌活性[J]. 农药学学报, 2020, 22(1): 27-34. doi: 10.16801/j.issn.1008-7303.2020.0011
引用本文: 范鑫鑫, 韩敏晖, 丁宇轩, 张学博, 李恒朝, 安杰. 氘标记稻瘟酯的合成及其杀菌活性[J]. 农药学学报, 2020, 22(1): 27-34. doi: 10.16801/j.issn.1008-7303.2020.0011
Xinxin FAN, Minhui HAN, Yuxuan DING, Xuebo ZHANG, Hengzhao LI, Jie AN. Synthesis and fungicidal activity of deuterated pefurazoate[J]. Chinese Journal of Pesticide Science, 2020, 22(1): 27-34. doi: 10.16801/j.issn.1008-7303.2020.0011
Citation: Xinxin FAN, Minhui HAN, Yuxuan DING, Xuebo ZHANG, Hengzhao LI, Jie AN. Synthesis and fungicidal activity of deuterated pefurazoate[J]. Chinese Journal of Pesticide Science, 2020, 22(1): 27-34. doi: 10.16801/j.issn.1008-7303.2020.0011

氘标记稻瘟酯的合成及其杀菌活性

doi: 10.16801/j.issn.1008-7303.2020.0011
基金项目: 国家自然科学基金青年项目 (21602248);国家重点研发计划 (2017YFD0200504)
详细信息
    作者简介:

    范鑫鑫,男,助理研究员,从事有机化学领域发明专利审查工作,E-mail:fanxinxin@cnipa.gov.cn

    通讯作者:

    李恒朝,共同通信作者 (Co-author for correspondence),男,农药学专业在读博士,E-mail:lihengzhao@cau.edu.cn

    安杰,通信作者 (Author for correspondence),女,教授,主要从事氘化学研究,E-mail:jie_an@cau.edu.cn

  • 中图分类号: TQ450.1; TQ455

Synthesis and fungicidal activity of deuterated pefurazoate

  • 摘要: 氘标记农药作为探针或者内标在农药代谢、毒理研究或者农药残留分析中发挥着重要作用。由于动力学同位素效应,C−D键比C−H键更为稳定,因此氘标记农药可能具有更长的半衰期,以及对非靶标生物更小的毒性。稻瘟酯是一种对水稻恶苗病和稻瘟病有良好防治效果的农用杀菌剂。本项研究利用单电子转移还原氘化反应和氘标记中间体,成功合成了4个不同位点被选择性氘代的稻瘟酯,其中3个化合物未见文献报道,并对其进行了杀菌活性测试。离体杀菌活性测试结果显示,上述4种氘代稻瘟酯对水稻稻瘟病菌和水稻恶苗病菌均具有良好的生物活性,与未被标记的稻瘟酯无显著差异。氘标记稻瘟酯未来可作为代谢、毒理研究的探针及农药残留分析中的内标。
  • 1  氘代丁苯那嗪和氘代甲萘威的结构式

    1.  Structual formular of deutetrabenazine and carbaryl-(methyl-d3)

    2  氘代化合物的合成策略

    2.  Strategies for the synthesis of deuterium labeled compounds

    3  新型单电子转移还原氘化反应

    3.  Novel single electron transfer reactions of reductive deuteration

    4  氘代稻瘟酯及其合成路线

    4.  The structural formula and synthesis route of deuterated pefurazoate

    5  氘代稻瘟酯合成方法的逆合成分析

    5.  Retro sythesis analysis of deuterated pefurazoate

    表  1  目标化合物1a~1d和稻瘟酯的 1H NMR 和 13C NMR

    Table  1.   1H NMR and 13C NMR spectra of compounds 1a-1d and pefurazoate

    化合物
    Compound
    1H NMR (300 MHz, CDCl3) 13C NMR (75 MHz, CDCl3)
    1a 8.13 (s, 1H), 7.49 (m, 1H), 7.45 (m, 1H), 7.11 (m, 1H), 6.38 – 6.33 (m, 2H), 5.78 (m, 1H), 5.08 – 4.92 (m, 2H), 4.72 (d, J = 16.3 Hz, 1H), 4.47 (d, J = 16.3 Hz, 1H), 3.99 (dd, J = 9.4, 5.7 Hz, 1H), 2.19 – 1.89 (m, 4H), 1.72 (t, J = 7.4 Hz, 2H), 0.74 (t, J = 7.5 Hz, 3H). 170.1, 151.4, 148.4, 143.4, 137.2 × 2, 129.3, 118.4, 115.7, 110.7 × 2, 65.1 (m), 62.5, 46.6, 30.0, 27.5, 21.6, 10.8.
    1b 8.16 (s, 1H), 7.51 (m, 1H), 7.47 (m, 1H), 7.13 (m, 1H), 6.40 – 6.36 (m, 2H), 4.74 (d, J = 16.2 Hz, 1H), 4.49 (d, J = 16.2 Hz, 1H), 4.01 (dd, J = 9.5, 5.7 Hz, 1H), 2.15 – 1.98 (m, 4H), 1.74 (t, J = 7.4 Hz, 2H), 0.77 (t, J = 7.5 Hz, 3H). 170.2, 151.8, 148.7, 143.3, 137.3, 137.0 (m), 130.2, 118.2, 115.2 (m), 110.7, 110.6, 64.8 (m), 62.4, 46.4, 29.8, 27.6, 21.7, 10.8.
    1c 7.47 (m, 1H), 6.40 – 6.35 (m, 2H), 5.80 (m, 1H), 5.08 – 4.97 (m, 2H), 4.74 (d, J = 16.3 Hz, 1H), 4.49 (d, J = 16.3 Hz, 1H), 4.16 (t, J = 6.6 Hz, 2H), 4.01 (dd, J = 9.4, 5.7 Hz, 1H), 2.18 – 1.97 (m, 4H), 1.75 (m, 2H), 0.77 (t, J = 7.5 Hz, 3H). 170.1, 151.7, 148.6, 143.2, 137.1, 137.0 (m), 129.6 (m), 117.8 (m), 115.6, 110.6, 110.5, 65.0, 62.4, 46.3, 29.9, 27.7, 21.6, 10.7.
    1d 7.47 (m, 1H), 6.40 – 6.35 (m, 2H), 5.80 (m, 1H), 5.09 – 4.97 (m, 2H), 4.74 (d, J = 16.3 Hz, 1H), 4.49 (d, J = 16.3 Hz, 1H), 4.01 (dd, J = 9.4, 5.7 Hz, 1H), 2.19 – 1.99 (m, 4H), 1.74 (t, J = 7.4 Hz, 2H), 0.77 (t, J = 7.4 Hz, 3H). 170.0, 151.7, 148.6, 143.2, 137.1, 136.8 (m), 129.4 (m), 117.6 (m), 115.5, 110.6, 110.5, 64.6 (m), 62.3, 46.3, 29.9, 27.5, 21.6, 10.7.
    稻瘟酯
    pefurazoate
    8.15 (s, 1H), 7.52 (m, 1H), 7.47 (m, 1H), 7.12 (m, 1H), 6.40 – 6.35 (m, 2H), 5.81 (m, 1H), 5.15 – 4.89 (m, 2H), 4.74 (d, J = 16.2 Hz, 1H), 4.49 (d, J = 16.2 Hz, 1H), 4.16 (t, J = 6.5 Hz, 2H), 4.01 (dd, J = 9.4, 5.7 Hz, 1H), 2.25 – 1.99 (m, 4H), 1.81 – 1.70 (m, 2H), 0.76 (t, J = 7.5 Hz, 3H). 169.8, 151.5, 148.4, 143.1, 137.0 × 2, 129.9, 117.9, 115.4, 110.5, 110.4, 64.8, 62.2, 46.2, 29.8, 27.50, 21.4, 10.5.
    下载: 导出CSV

    表  2  氘代稻瘟酯对水稻稻瘟病菌和水稻恶苗病菌的离体活性

    Table  2.   In vitro antibacterial activity of the deuterated pefurazoate against Pyricularia oryzae and Gibberella fujikuroi

    化合物
    Compound
    水稻稻瘟病菌 Pyricularia oryzae水稻恶苗病菌 Gibberella fujikuroi
    回归方程 Regression equation相关系数 rEC50/(mg/L) 回归方程 Regression equation相关系数 rEC50/(mg/L)
    稻瘟酯 pefurazoate y = 0.801 2x + 4.819 1 0.986 4 1.68 y = 0.849 4x + 5.580 7 0.984 9 0.20
    1a y = 0.723 2x + 4.870 6 0.998 0 1.51 y = 1.116 4x + 5.581 8 0.949 2 0.19
    1b y = 0.658 8x + 4.848 3 0.995 0 1.70 y = 0.961 8x + 5.718 0 0.963 0 0.18
    1c y = 0.813 4x + 4.782 0 0.974 7 1.85 y = 1.073 6x + 5.791 4 0.965 2 0.18
    1d y = 0.752 4x + 4.808 0 0.984 9 1.80 y = 1.102 4x + 5.800 0 0.964 4 0.19
    下载: 导出CSV
  • [1] PIRALI T, SERAFINI M, CARGNIN S, et al. Applications of deuterium in medicinal chemistry[J]. J Med Chem, 2019, 62(11): 5276-5297. doi: 10.1021/acs.jmedchem.8b01808
    [2] CHENG T D, SHELVER W L, HONG C C, et al. Urinary excretion of the beta-adrenergic feed additives ractopamine and zilpaterol in breast and lung cancer patients[J]. J Agric Food Chem, 2016, 64(40): 7632-7639. doi: 10.1021/acs.jafc.6b02723
    [3] MUTLIB A E. Application of stable isotope-labeled compounds in metabolism and in metabolism-mediated toxicity studies[J]. Chem Res Toxicol, 2008, 21(9): 1672-1689. doi: 10.1021/tx800139z
    [4] ATZRODT J, DERDAU V, KERR W J, et al. Deuterium- and tritium-labelled compounds: applications in the life sciences[J]. Angew Chem Int Ed Engl, 2018, 57(7): 1758-1784. doi: 10.1002/anie.201704146
    [5] KAINO T, JINGUJI K, NARA S. Low loss poly(methylmethacrylate-d8) core optical fibers[J]. Appl Phys Lett, 1983, 42(7): 567-569. doi: 10.1063/1.94030
    [6] GANT T G. Using deuterium in drug discovery: leaving the label in the drug[J]. J Med Chem, 2014, 57(9): 3595-3611. doi: 10.1021/jm4007998
    [7] DART A. Cancer immunotherapy: Rewiring cancer cells[J]. Nat Rev Drug Discov, 2017, 16(12): 828.
    [8] KATSNELSON A. Heavy drugs draw heavy interest from pharma backers[J]. Nat Med, 2013, 19(6): 656. doi: 10.1038/nm0613-656
    [9] KOIKE Y, KOIKE K. Progress in low-loss and high-bandwidth plastic optical fibers[J]. J Polym Sci Part B: Polym Phys, 2011, 49(1): 2-17. doi: 10.1002/polb.22170
    [10] SCHMIDT C. First deuterated drug approved[J]. Nat Biotechnol, 2017, 35(6): 493-494. doi: 10.1038/nbt0617-493
    [11] VANDERFORD B J, SNYDER S A. Analysis of pharmaceuticals in water by isotope dilution liquid chromatography/tandem mass spectrometry[J]. Environ Sci Technol, 2006, 40(23): 7312-7320.
    [12] YANG X J, DU Z X, LIN A J, et al. Simultaneous determination of neutral, basic and acidic pesticides in aquatic environmental matrices by solid-phase extraction and liquid chromatography electrospray ionization mass spectrometry[J]. Analytical Methods, 2013, 5(8): 2083. doi: 10.1039/c3ay26095j
    [13] FANG K, JIANG Z J, WANG J, et al. Simulation of nonylphenol degradation in leafy vegetables using a deuterated tracer[J]. Environ Sci: Processes Impacts, 2015, 17(7): 1323-1330. doi: 10.1039/C5EM00073D
    [14] 除草剂残留量检测方法第5部分: 液相色谱-质谱质谱法测定食品中硫代氨基甲酸酯类除草剂残留量: GB 23200.5—2016[S].

    National food safety standards: determination of thiocarbmate herbicide residues in foods liquid chromatography-mass spectrometry: GB 23200.5—2016[S].
    [15] KURIHARA N. Application of deuterium isotope effects to the xenobiotic metabolism study[J]. J Mass Spectrom Soc Jpn, 1998, 46(3): 157-172. doi: 10.5702/massspec.46.157
    [16] NGUYEN B C, CHOMPOO J, TAWATA S. Insecticidal and nematicidal activities of novel mimosine derivatives[J]. Molecules, 2015, 20(9): 16741-16756. doi: 10.3390/molecules200916741
    [17] ATZRODT J, DERDAU V, FEY T, et al. The renaissance of H/D exchange[J]. Angew Chem Int Ed Engl, 2007, 46(41): 7744-7765. doi: 10.1002/anie.200700039
    [18] LOH Y Y, NAGAO K, HOOVER A J, et al. Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds[J]. Science, 2017, 358(6367): 1182-1187. doi: 10.1126/science.aap9674
    [19] YU R P, HESK D, RIVERA N, et al. Iron-catalysed tritiation of pharmaceuticals[J]. Nature, 2016, 529(7585): 195-199. doi: 10.1038/nature16464
    [20] SCHOFIELD J, DERDAU V, ATZRODT J, et al. Effect of deuteration on metabolism and clearance of Nerispirdine (HP184) and AVE5638[J]. Bioorg Med Chem, 2015, 23(13): 3831-3842. doi: 10.1016/j.bmc.2015.03.065
    [21] UPSHUR M A, CHASE H M, STRICK B F, et al. Vibrational mode assignment of alpha-pinene by isotope editing: one down, seventy-one to go[J]. J Phys Chem A, 2016, 120(17): 2684-2690. doi: 10.1021/acs.jpca.6b01995
    [22] RODRIGUEZ S, CAMPS F, FABRIAS G. Synthesis of gem-dideuterated tetradecanoic acids and their use in investigating the enzymatic transformation of (Z)-11-tetradecenoic acid into (E,E)-10,12-tetradecadienoic acid[J]. J Org Chem, 2001, 66(24): 8052-8058. doi: 10.1021/jo010560w
    [23] DING Y, LUO S, ADIJIANG A, et al. Reductive deuteration of nitriles: the synthesis of alpha, alpha-dideuterio amines by sodium-mediated electron transfer reactions[J]. J Org Chem, 2018, 83(19): 12269-12274. doi: 10.1021/acs.joc.8b01730
    [24] HAN M, MA X, YAO S, et al. Development of a modified bouveault-blanc reduction for the selective synthesis of alpha, alpha-dideuterio alcohols[J]. J Org Chem, 2017, 82(2): 1285-1290. doi: 10.1021/acs.joc.6b02950
    [25] LI H, ZHANG B, DONG Y, et al. A selective and cost-effective method for the reductive deuteration of activated alkenes[J]. Tetrahedron Lett, 2017, 58(28): 2757-2760. doi: 10.1016/j.tetlet.2017.05.092
    [26] ZHANG B, LI H, DING Y, et al. Reduction and reductive deuteration of tertiary amides mediated by sodium dispersions with distinct proton donor-dependent chemoselectivity[J]. J Org Chem, 2018, 83(11): 6006-6014. doi: 10.1021/acs.joc.8b00617
    [27] HAN M, DING Y, YAN Y, et al. Transition-metal-free, selective reductive deuteration of terminal alkynes with sodium dispersions and EtOD- d1[J]. Org Lett, 2018, 20(10): 3010-3013. doi: 10.1021/acs.orglett.8b01036
    [28] WADA T, HIRAMATU M, TAKENAKA M, et al. Development of a new seed disinfectant, pefurazoate[J]. J Pestic Sci, 1999, 24(2): 230-240. doi: 10.1584/jpestics.24.230
    [29] TAKENAKA M, SAKAI S, NISHIDA H, et al. Degradation and adsorption of a seed fungicide pefurazoate in paddy soil[J]. J Pestic Sci, 1991, 16(4): 631-639. doi: 10.1584/jpestics.16.631
    [30] 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: 中国农业大学出版社, 2006.

    Pesticides guidelines for laboratory bioactivity tests: Part 2: Petri plate test for determining fungicide inhibition of mycelial growth: NY/T1156. 2—2006[S]. Beijing: China Agriculture Press, 2006.
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  • 收稿日期:  2019-07-26
  • 录用日期:  2019-09-06
  • 刊出日期:  2020-02-01

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