基于momfluorothrin的新型卫生用菊酯类化合物的合成

    Synthesis of novel hygienic pyrethroid compounds based on momfluorothrin

    • 摘要: 开发新结构活性化合物对蚊虫抗药性治理具有重要意义。本研究以momfluorothrin为基础,设计合成了17个新型拟除虫菊酯类化合物,其结构均经过质谱及核磁确证。目标化合物蚊香圆筒活性测试显示,2,3,5,6-四氟-4-甲氧甲基苄基(1R,3R)-3-((Z)-2-氰基乙烯基)-2,2-二甲基-环丙羧酸酯(1a)、2,3,5,6-四氟苄基(1R,3R)-3-((Z)-2-氰基乙烯基)-2,2-二甲基-环丙羧酸酯(2a)、2,3,4,5,6-五氟苄基(1R,3R)-3-((Z)-2-氰基乙烯基)-2,2-二甲基-环丙羧酸酯(3a)、2,3,5,6-四氟-4-甲基苄基(1R,3R)-3-((Z)-2-氰基乙烯基)-2,2-二甲基-环丙羧酸酯(4a)和3-苯氧基-4-氟苄基(1R,3R)-3-((Z)-2-氰基乙烯基)-2,2-二甲基-环丙羧酸酯(11) 5个化合物对淡色库蚊的击倒活性优于四氟苯菊酯及母体momfluorothrin,其中化合物2a活性最高,其质量分数为0.05%的蚊香对淡色库蚊的半数击倒时间 (KT50) 为4.61 min;进一步测定发现,0.9%化合物2a电热蚊香液的圆筒试验击倒活性(KT50值为4.56~4.98 min)可达到市售0.31%四氟甲醚菊酯蚊香及1.5%四氟醚菊酯蚊香水平,模拟现场活性则略优于0.31%四氟甲醚菊酯蚊香。毒性测定显示,化合物2a对大鼠的急性经口毒性、经皮毒性和吸入毒性均为微毒,其半数致死剂量 (LD50) > 5000 mg/kg (bw)。同时兼具较高的杀虫活性及较低的毒性,表明化合物2a具有开发为高效、低毒型电热蚊香液的潜力。

       

      Abstract: The synthesis of novel structured active compounds is of great significance for the management of mosquito resistance to insecticides. In this study, based on momfluorothrin, 17 novel pyrethroid compounds were designed and synthesized, all of which were structurally confirmed by mass spectrometry and nuclear magnetic resonance spectroscopy. Cylinder tests of mosquito coil biological activity revealed that five of these compounds (2,3,5,6-tetrafluoro-4-methoxymethylbenzyl(1R,3R)-3-((Z)-2-cyanovinyl)-2,2-dimethylcyclopropanecarboxylate (1a), 2,3,5,6-tetrafluorobenzyl(1R,3R)-3-((Z)-2-cyanovinyl)-2,2-dimethylcyclopropanecarboxylate (2a), 2,3,4,5,6-pentafluorobenzyl(1R,3R)-3-((Z)-2-cyanovinyl)-2,2-dimethylcyclopropanecarboxylate (3a), 2,3,5,6-tetrafluoro-4-methylbenzyl(1R,3R)-3-((Z)-2-cyanovinyl)-2,2-dimethylcyclopropanecarboxylate (4a), and 3-phenoxy-4-fluorobenzyl(1R,3R)-3-((Z)-2-cyanovinyl)-2,2-dimethylcyclopropanecarboxylate (11)) exhibited better knockdown activity against Culex pipiens pallens than tetramethylfluthrin and momfluorothrin, with compound 2a showing the highest activity KT50 = 4.61 min, 0.05% (m/m). Further cylinder test of the 0.9% compound 2a liquid vaporizer showed that its knockdown activity (KT50 = 4.56-4.98 min) was comparable to that of commercially available 0.31% dimefluthrin-based and 1.5% tetramethylfluthrin-based products, and its analogous site activity was slightly superior to that of the 0.31% dimefluthrin-based product. Acute toxicity tests of compound 2a indicated that it is slightly toxic to rats in terms of acute oral toxicity, acute percutaneous toxicity, and acute inhalation toxicity with LD50 values > 5000 mg/kg (bw). The favorable activity and low toxicity of compound 2a make it more suitable for the development of low-toxicity liquid vaporizer.

       

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