新型胍类化合物的合成及甘草次酸的结构修饰
摘要
在世界上，往往以除草剂在农药中所占比例来衡量一个国家的农药水平。目前(2004年统计)，世界三大类农药的平均比例是：除草剂∶杀虫剂∶杀菌剂=46.7∶28.9∶19.3，而在我国为17.0∶69.6∶10.4，这正是我国农药的落后所在。我国是一个农业大国，因此发展高效、低毒、对环境友好的绿色除草剂，对我国农业发展有着十分重要的意义
近十年来，农药发展的重要趋向是杂环化合物在农药发展中显示了十分重要的作用。通过查阅文献，发现异噁唑类化合物具有多种生物活性，迄今为止已开发成为除草剂品种的异噁唑衍生物已达十多种。近几年来仍不断有新型的异噁唑衍生物被研究和开发
而近来胍类结构化合物也成为药物研究中的一个热点，它们具有结构简单、活性优良、作用谱广、毒性小等优点而备受世界许多化学公司的重视。活性片段拼接的方法在新农药创制中起十分重要的作用，我们采用药物设计原理中的拼合原理和类似物原理设计合成了一系列含有异噁唑环的胍基化合物。
甘草次酸是中药甘草中的活性成分之一，具有抗炎、止痛、抗病毒、抗癌、抗艾滋病毒等活性。但是临床上应用该药常伴有假醛固酮增多症，表现为患者长期用药后出现水肿、湿疹、低血钾等现象，限制了其在临床上的应用。因此有目的的修饰其结构以寻找高效、毒副作用低的新药具有重要的药学价值和现实意义。
本文在前人研究的基础上，结合甘草次酸的构效关系，采用拼合原理和类似物原理设计合成了一系列异噁唑杂环胍衍生物，并将其引入甘草次酸，首次合成了一系列甘草次酸异噁唑杂环酰胍衍生物。通过IR、~1H NMR、ESI-MS等分析方法确定了它们的化学结构。
Isoxazole derivatives belong to the most active classes of compounds possessing a broad spectrum of biological activity, and are widely used in Pharmaceuticals and agrochemicals, among which a variety of reported compounds as good fungicides are commercially available already.
The guanidine-containing compounds have also been employed as anti-microbials and fungicides on a considerable scale. The drags containing guanidine framework are not only easy to transport, but also make the functions of absorption and osmosis more selective due to the good solubility of their various acid salts in aqueous solution.
According to the above facts, combining the isoxazole nucleus and guanidine framework might lead to more efficient herbicides.
Glycyrrhetinic acid is one of the active ingredients of the licorice root, and it has a great variety of pharmacological properties including anti-inflammatory, anti-allergic, anti-nociceptive, anti-ulcer, anti-tumor, and anti-viral. However, a side-effect (induction of edema and hypertension) has been observed in patients given high doses of glycyrrhizin and glycyrrehtinic acid for prolonged period. This side-effect, a mineral corticoid-like action noted as pseudoaldosteronism, is due to the inhibition of the metabolic clearance of endogenous corticoid with the retention of Na+ and water and excretion of K+. Thus it is very important to modify its structure to look for more active drugs.
Based on the others' study and according to the connection between the drug and the receptor, a series of novel glychrrhetinic acid isoxazole derivatives have been firstly synthesized and their chemical structures were confirmed by the methods of IR, ~1H NMR, and ESI-MS.
近十年来，农药发展的重要趋向是杂环化合物在农药发展中显示了十分重要的作用。通过查阅文献，发现异噁唑类化合物具有多种生物活性，迄今为止已开发成为除草剂品种的异噁唑衍生物已达十多种。近几年来仍不断有新型的异噁唑衍生物被研究和开发
而近来胍类结构化合物也成为药物研究中的一个热点，它们具有结构简单、活性优良、作用谱广、毒性小等优点而备受世界许多化学公司的重视。活性片段拼接的方法在新农药创制中起十分重要的作用，我们采用药物设计原理中的拼合原理和类似物原理设计合成了一系列含有异噁唑环的胍基化合物。
甘草次酸是中药甘草中的活性成分之一，具有抗炎、止痛、抗病毒、抗癌、抗艾滋病毒等活性。但是临床上应用该药常伴有假醛固酮增多症，表现为患者长期用药后出现水肿、湿疹、低血钾等现象，限制了其在临床上的应用。因此有目的的修饰其结构以寻找高效、毒副作用低的新药具有重要的药学价值和现实意义。
本文在前人研究的基础上，结合甘草次酸的构效关系，采用拼合原理和类似物原理设计合成了一系列异噁唑杂环胍衍生物，并将其引入甘草次酸，首次合成了一系列甘草次酸异噁唑杂环酰胍衍生物。通过IR、~1H NMR、ESI-MS等分析方法确定了它们的化学结构。
Isoxazole derivatives belong to the most active classes of compounds possessing a broad spectrum of biological activity, and are widely used in Pharmaceuticals and agrochemicals, among which a variety of reported compounds as good fungicides are commercially available already.
The guanidine-containing compounds have also been employed as anti-microbials and fungicides on a considerable scale. The drags containing guanidine framework are not only easy to transport, but also make the functions of absorption and osmosis more selective due to the good solubility of their various acid salts in aqueous solution.
According to the above facts, combining the isoxazole nucleus and guanidine framework might lead to more efficient herbicides.
Glycyrrhetinic acid is one of the active ingredients of the licorice root, and it has a great variety of pharmacological properties including anti-inflammatory, anti-allergic, anti-nociceptive, anti-ulcer, anti-tumor, and anti-viral. However, a side-effect (induction of edema and hypertension) has been observed in patients given high doses of glycyrrhizin and glycyrrehtinic acid for prolonged period. This side-effect, a mineral corticoid-like action noted as pseudoaldosteronism, is due to the inhibition of the metabolic clearance of endogenous corticoid with the retention of Na+ and water and excretion of K+. Thus it is very important to modify its structure to look for more active drugs.
Based on the others' study and according to the connection between the drug and the receptor, a series of novel glychrrhetinic acid isoxazole derivatives have been firstly synthesized and their chemical structures were confirmed by the methods of IR, ~1H NMR, and ESI-MS.
引文
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