含喹唑啉硫醚的α 氨基膦酸酯的合成及生物活性研究-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 1 摘要 喹唑啉类化合物具有高效广谱生物活性，如抗肿瘤，抗炎，杀菌，杀螨等， 在医药和农药领域有着广泛的应用。α-氨基膦酸酯作为天然氨基酸类似物，也 是一类具有良好生物活性的化合物，被广泛的用作杀菌剂、除草剂、抗病毒剂， 因而具有广阔的发展前景。为了创制高活性的抗植物病毒药物，本文采用活性 基团拼接法，以邻氨基苯甲酸为起始原料，经闭环，氯化，醚化，类 Mannich 反应将喹唑啉和硫醚基团引入到α-氨基膦酸酯结构中，设计合成了 24 个结构新 颖的含喹唑啉硫醚的α-氨基膦酸酯类化合物。 通过 IR、1H NMR、13C NMR、31P NMR 和元素分析对目标化合物的结构 进行了表征，初步研究了该系列化合物的波谱性质和一般规律。对中间体及目 标化合物的合成条件进行了优化。 采用半叶枯斑法，对部分目标化合物进行了抗 TMV 活性筛选，实验结果 表明，在 500 μg/mL 浓度下，部分化合物表现出一定的抗 TMV 活性，其中化 合物 5c 的抗 TMV 活性较好，达到 46.3%。 采用半叶枯斑法，对部分目标化合物进行了抗 CMV 活性筛选，实验结果 表明，在 500 μg/mL 浓度下，部分化合物表现出一定的抗 CMV 活性，其中化 合物 5c，5o 的抗 CMV 活性较好，分别达到 48.4%，48.8%。 关键词： 喹唑啉；α-氨基膦酸酯；合成；生物活性 中文分类号：O626.24 Abstract Quinazoline compounds with efficient and broad biological activities, are widely used in the field of medicine and pesticides. The α-amino phosphonates as analogues of natural amino acids, have been found to show good biological activities and are widely used as fungicides, herbicides, antiviral agents, so they have a bright future. With the aim to creat novel and highly active antiviral agents for plants, according to the principle of combination of bioactive substructure, using anthranilic acid as the starting material, through closed-loop, chloride, etherification, and then via Mannich type reaction, we designed and synthesized 24 new compounds by bringing quinazoline and sulfide moieties into α-amino phosphonates framework. Their structures of the target compounds have been confirmed by IR spectroscopy, 1H NMR, 13C NMR, 31P NMR and elemental analyses. We disscussed the spectral properties and laws of the target compounds. The preliminary biological activities of the title compounds were evaluated by half-leaf method. The results showed that some of them exhibited certain anti-TMV activities. The target compound 5c showed good curative activities, with value of 46.3% at 500 μg/mL. In addition, some α-amino phosphonates derivatives also showed good curative activities against CMV at 500 μg/mL, such as 5c and 5o with valu