含α-氨基膦酸酯的哒嗪衍生物的合成与生物活性研究-农药学专业论文.docxVIP

贵州大学 贵州大学 2010 届硕士研究生学位论文 PAGE PAGE 2 Abstract Pyridazine derivatives are known for their wide range of biological activities as insecticides, fungicides, herbicides, plant virucides and antiviral agents, and so on, and are highly effective, safe and environmental friendly. So they have been widely applied to pesticides. To investigate novel antiviral agent against tobacco mosaic virus (TMV), thirty pyridazine derivatives containing an α-aminophosphonate moiety were designed and synthesized using 2-phenyl-4-chloro-5-(4-aminophenylthio)pyridazin-3(2H)-one, aldehydes, and O,O- dialkylphosphites with principle combination of active groups. The structures of all compounds were verified by 1H NMR, 13C NMR, 31P NMR, IR and element analysis. Under optimized conditions, the best result was obtained when the Mannich reaction was carried out for 7 h in toluene at its reflux temperature. The products were obtained in good to high chemical yield (51%-79%). Half-leaf method was used to determine curative effects of the title compounds in vivo. The bioassay results also showed at 500 μg/mL, the title compounds had anti-tobacco mosaic virus (TMV). The compounds C26 and C21 had similar curative effects against TMV (inhibitory rate: 53.8% and 50.5%) as the commercial product Ningnanmycin (55.6%). Keywords: pyridazine; aminophosphonate; synthesis; antiviral activity. 前 言 哒嗪类化合物是一类具有广泛生物活性的杂环化合物，其中不少品种还具 有高效、低毒、广谱、选择性高、持效期长及对作物安全等特点。自 1949 年， Schoene 和 Hoffmann 首次报道了 4-羟基哒嗪酮具有强烈抑制植物细胞分裂的特 性，并作为植物生长调节剂应用在农业生产中以来，哒嗪类化合物已成为农药 研究的热点之一。以哒嗪环为母体进行结构修饰相继成功开发了多个 杀虫剂、 杀菌剂、植物生长调节剂等新品种，如杀虫(杀螨)剂 NC-196、杀菌剂哒菌清 (diclomezine)、除草剂杀草敏(chloridazon)、植物生长调节苯哒嗪钾(clofencet)等。 近十年来，大量文献报道了哒嗪类化合物具有广泛的生物活性，如杀菌(刘卫东 等，2005; Kandile, etal, 2008)、杀虫杀螨(Ruediger, etal, 2006; 凌云等，2009)、 除草(胡方中等，2006; Liu, etal, 2008)、抗病毒(邹霞娟等，2002; Rashad, etal, 2007)等。 O Cl Cl N  O N NH Cl N H O O N O H3C O Cl N N NH2 NC-196 diclomezine chloridazon COOK Cl N O N clofencet α-氨基膦酸及酯作为天然氨基酸的类似物，自 20 世纪 50 年代末 Horiguchi 从动物体