新型氮杂环类化合物的分子设计、合成及生物活性研究

【作者】 戴红；

【导师】 方建新；

【作者基本信息】 南开大学 ， 农药学， 2009， 博士

【摘要】 氮杂环类化合物大多具有广谱生物活性,在植物保护方面具有重要的应用。目前,含氮杂环化合物已成为新药创制研究的重点领域之一。噻唑、吡啶、吡唑肟及三唑类化合物是几类重要的含氮杂环化合物,其研究内容相当广泛。为了从含氮杂环类化合物中寻找高活性的先导化合物,结合噻唑、吡啶、吡唑肟及三唑类化合物的结构特征及活性信息,应用分子合理设计及活性亚结构拼接等方法,设计并合成了10个系列共133个新型含氮杂环化合物。所有新化合物的结构均经~1H NMR和元素分析确证,部分化合物经质谱及X-衍射方法进一步验证其结构。利用苯甲醛、苯甲酰氯及苯甲酰异硫氰酸酯与4-((2-氰基亚胺基-1,3-噻唑烷-3-基)甲基)-2-氨基噻唑反应制备了3个系列共46个含有2-氰基亚胺基-1,3-噻唑烷环的类新烟碱类噻唑衍生物。生物活性测试结果表明,部分化合物具有一定的杀菌和植物生长调节活性。采用活性因子拼接和生物电子等排方法,将重要杂环2-氯-5-甲基噻唑和2-氯-5-甲基吡啶环引入到吡唑肟醚分子结构中,设计并合成了6个系列新型含噻唑基或吡啶基的吡唑肟醚化合物,对目标化合物的合成条件进行了探讨,最终以较高收率得到目标产物。生物活性测试结果表明,部分化合物表现出良好的杀蚜虫活性和一定的植物生长调节活性。借鉴六氟丙酮等羰基化合物向其偕二醇成功转化的经验,设计并合成了12个新型含吡啶基和三唑基的偕二醇类化合物,在完成酮式向醇式转化过程中,尝试了不同的方法,最终选用乙酸乙酯作溶剂,不加任何催化剂加热回流的方法,以较高收率制备出目标物。本论文合成的偕二醇化合物可作为金属有机合成重要的配体。生物活性测试结果表明,部分化合物表现出较好的植物生长调节活性。更多还原

【Abstract】 Most of heterocyclic compounds containing nitrogen possess diverse biological activities.They are widely used in plant protection.Researches in novel compounds containing N-heterocycles have become one of the significant fields of researches in new agrochemicals.Meanwhile,thiazole derivatives,pyridine-based compounds, pyrazole oximes and 1H-1,2,4-triazole derivatives are several important sorts of heterocyclic compounds containing nitrogen.They are widely investigated by many agricultural and medicinal chemists.In order to search for novel lead compounds with good bioactivities,we analyzed the chemical structure and structure-activity relationships of thiazoles, pyridine derivatives,pyrazole oximes and 1H-1,2,4-triazole derivatives,designed and synthesized ten series of one hundred and thirty-three new compounds containing N-heterocycles by following the principle of combination of bioactive sub-structures.Their structures were confirmed by ~1H NMR,elemental analysis,and some compounds were also determined by MS and X-ray diffraction analysis.Three series of fourty-six new compounds containing 2-cyanoimino-1,3-thiazolidine and thiazole rings were synthesized by the reaction of 2-cyanoimino-3-(2-aminothiazol-4-ylmethyi) thiazolidine with various substituted benzaldehydes,benzoyl chlorides,and benzoyl isothiocyanates.Preliminary bioassay showed that some of the target compounds exhibited fungicidal and plant growth regulatory activities to some extent.Six series of pyrazole oxime derivatives containing important 2-chloro-5-methyl-thiazole or 2-chloro-5-methyl-pyridine ring were synthesized by the methods of union of active groups and bioisosterism.We had tried various reaction conditions for the synthesis of title compounds,and the target compounds were obtained in good yields.Some of the target compounds exhibited good insecticidal and certain plant growth regulatory activities.According to the experience in high transformation of 1,1,1,3,3,3- hexafluoropropan-2-one and other carbonyl compounds to their hydrates,twelve novel gem-diols containing pyridyl and triazolyl groups were designed and synthesized.We investigated various reaction conditions for the synthesis of gem-diols.Finally,the title Compounds were obtained in satisfactory yields by using ethyl acetate as the solvent without addition of any catalyst.The gem-diols obtained above can be acted as the vital materials for the synthesis of the metal-organic compounds.Preliminary bioassay indicated that some of the target compounds displayed good plant growth regulatory activities.更多还原