【作者】 王婷；

【导师】 王存德； 孙良；

【作者基本信息】 扬州大学 ， 制药工程（专业学位）， 2019， 硕士

【摘要】 含氮杂环是许多具有重要生物活性天然有机化合物和合成药物的基本骨架。近年来,在创新性药物小分子的设计和合成中,含氮杂环往往作为药效核心环单元使用,而通过构建含氮杂环后衍生,可以非常容易地获得具有潜在生物活性的有机小分子。结合本课题组对含氮杂环化合物前期合成的研究结果,本文分别以取代β-芳基硝基乙烯和取代水杨醛为反应底物,设计了合成三种不同含氮杂环单元的化合物2,4,6-三芳基吡啶衍生物、1-硝基中氮茚衍生物、苯并噁嗪衍生物。第一部分:研究了取代2,4,6-三芳基吡啶衍生物的合成方法。以取代β-芳基硝基乙烯和取代吡啶季铵盐为反应底物在酸性溶剂中反应。经过反应条件的优化,共合成18个目标产物,收率为69-85%,所有的化合物都经过了核磁共振氢谱图、核磁共振碳谱图、红外、高分辨质谱等方法表征,对其中一个化合物进行了单晶X-衍射分析确定结构。第二部分:研究了取代1-硝基中氮茚衍生物的合成方法。以取代β-芳基硝基乙烯和取代吡啶季铵盐为反应底物,在DBU的催化下,高选择性地合成了一系列1-硝基中氮茚衍生物。经过反应条件的优化,共合成了 20个目标产物,收率为70-90%。所有的化合物都经过了核磁共振氢谱图、核磁共振碳谱图、红外、高分辨质谱等方法表征,对其中一个化合物进行了单晶X-衍射分析确定结构。第三部分:以取代水杨醛为反应底物在K2CO3作用下,经过两步反应,最终合成了 7个苯并噁嗪衍生物,收率为70-80%。以取代水杨醛和丁炔二酸二酯类化合物为底物,经过对条件的优化和筛选,确定最佳反应条件。最终合成8个含有双键侧链的二苯并噁嗪类衍生物,收率为60-83%。所有的化合物都经过了核磁共振氢谱图、核磁共振碳谱图、红外、高分辨质谱等方法表征,对其中两个化合物进行了单晶X-衍射分析确定结构。更多还原

【Abstract】 Heterocycles containing the nitrogen are the basic skeletons of numerous natural organic compounds and synthetic medicines with important biological activities.In recent years,heterocycles with the nitrogen are used widely as important pharmacophores in the design and synthesis of the innovative medicines,a large number of organic compounds with the nitrogen were synthesized for the researches of biological activities.Based on our previous researches of the preparation of heterocyclic compounds containing the nitrogen,in this paper,the synthesis of 2,4,6-triarylpyridine derivatives,1-nitroindolizine derivatives and benzoxazine derivative from substituted β-nitrostyrenes and substituted salicylic aldehydes has been developed.The first part:2,4,6-trisubstituted pyridines were synthesized via one-pot reaction ofβ-nitrostyrenes,pyridine quaternary ammonium salts and ammonium acetate in the acidic conditions.Eighteen products were obtained under the optimized reaction conditions in yields of 69-85%.All compounds were characterized by NMR,IR and HRMS spectroscopy.One of the compounds was subjected to single crystal X-ray diffraction analysis to determine the structure.The second part:A highly selective method was developed for the synthesis of 1-nitroindolizine derivatives via the DBU-mediated cycloaddition reaction of β-nitrostyrenes and pyridine quaternary ammonium salts.1-Nitroindolizine derivatives were gained in 70-90%yields.All compounds were characterized by NMR,IR and HRMS spectroscopy.The single crystal structure of one 1-nitroindolizine was confirmed by X-ray diffraction method.The third part:Benzoxazine derivatives were synthesized via one-pot reaction of substituted salicylicaldehydes and ammonium acetate in the presence of potassium carbonate.Seven products were synthesized under optimized the reaction conditions in 70-80%yield.Then,an pseudo four-component reaction of substituted 2-hydroxybenzaldehydes,ammonium acetate and different dialkyl but-2-ynedioates for the preparation of epiminodibenzo[b,f][1,5]dioxocin-13-yl-but-2-enedioates was developed.Eight products were yielded under the optimized reaction conditions in 60-83%.All compounds were characterized by NMR,IR and HRMS spectroscopy.The single crystal structures of two desired products were confirmed by X-ray diffraction method.更多还原