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含硫醚和砜亚结构的新型芳香酰胺类衍生物的设计、合成及生物活性
Xuewen Hua, Nannan Liu, Sha Zhou, Leilei Zhang, Hao Yin, Guiqing Wang, Zhijin Fan, Yi Ma
工程（英文） ›› 2020, Vol. 6 ›› Issue (5) : 553-559.
PDF(1066 KB)
PDF(1066 KB)
含硫醚和砜亚结构的新型芳香酰胺类衍生物的设计、合成及生物活性
Design, Synthesis, and Biological Activity of Novel Aromatic Amide Derivatives Containing Sulfide and Sulfone Substructures
近年来，土壤线虫危害日趋严重，然而市场上应用的杀线虫剂品种匮乏且结构单一。氟吡菌酰胺（fluopyram）是德国拜耳公司开发的琥珀酸脱氢酶抑制剂（SDHI）类杀菌剂，因其高效和作用机制新颖被广泛用于土壤线虫的防治。本文以杀菌、杀线虫剂氟吡菌酰胺为分子骨架，通过引入硫醚和砜亚结构，设计合成了两个系列的结构新颖的目标化合物，并经核磁共振氢谱（1H NMR）、核磁共振碳谱（13C NMR）和高分辨质谱（HRMS）表征新结构。经生物活性测试发现，与对照药氟吡菌酰胺相比，大多数目标化合物在200 μg·mL−1浓度下显示出优异的杀线虫活性，而当浓度降低为100 μg·mL−1时，线虫死亡率大大降低，其中，化合物I-11、II-6除外。在杀菌活性方面，化合物I-9具有优异的抑菌率，其分子对接结果将为高活性杀菌先导化合物的设计和探索提供重要的理论指导。
In recent years, the damage caused by soil nematodes has become increasingly serious; however, the varieties and structures of the nematicides available on the market are deficient. Fluopyram, a succinate dehydrogenase inhibitor (SDHI) fungicide developed by Bayer AG in Germany, has been widely used in the prevention and control of soil nematodes due to its high efficiency and novel mechanism of action. In this paper, two series of novel target compounds were designed and synthesized with nematicidal and fungicidal fluopyram as the molecular skeleton in order to introduce sulfide and sulfone substructures. The structures were identified and characterized by 1H nuclear magnetic resonance (NMR), 13C NMR, and high-resolution mass spectrometer (HRMS). The bioassays revealed that most of the compounds showed excellent nematicidal activities at 200 µg･mL−1 in comparison with fluopyram, while the nematode mortality rate dropped sharply at 100µg･mL−1, except for compounds I-11 and II-6. In terms of fungicidal activity, compound I-9 was discovered to have an excellent inhibitory rate, and a molecular docking simulation was performed that can provide important guidance for the design and exploration of efficient fungicidal lead compounds.
Synthesis / Nematicidal activity / Fungicidal activity / Molecular docking
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