【作者】 谢松；

【导师】 陈华；

【作者基本信息】 河北大学 ， 化学生物学， 2024， 硕士

【摘要】 由于多组分反应具有较高的反应效率,可以构建复杂的分子结构,特别是稠杂氮杂类化合物。[4+2]环加成反应是构建六元环的有效方法,因此在复杂天然产物、手性药物的化学合成和生物合成方面有广泛的应用。亚氨基糖又称氮杂糖,是一类具有重要生物活性的含氮碳水化合物,常作为糖苷酶抑制剂,在医药领域有着广泛的应用前景。目前,构建复杂含氮杂环分子的方法多种多样,但合成稠杂氮杂糖的方法十分有限。因此,本文主要将常见的环化反应用于构建合成结构新颖的稠杂氮杂糖,为该类化合物的研发和应用提供基础。本文第一部分以D-核糖为原料,通过丙叉基保护、对甲苯磺酰基(Ts)活化,在室温下与苯胺形成亚氨离子中间体,然后与乙烯基乙醚通过[4+2]型的aza-Diels-Alder反应合成稠杂三环氮杂糖衍生物,同时通过Mannich反应合成亚氨基碳糖苷衍生物。在60℃加热条件下亚氨基正离子可以互变为烯胺,接着与苯胺和乙烯基乙醚形成的亚胺通过[4+2]型的aza-Diels-Alder反应形成四氢喹啉并氮杂糖衍生物。所有新合成的化合物都可以很好的进行丙叉保护基的脱除。本文第二部分以D-核糖为原料,通过丙叉基保护、对甲苯磺酰基(Ts)活化,在80℃加热条件下与苯胺形成烯胺中间体,接着与环烯酮(环戊烯酮/环己烯酮)互变的二烯醇结构通过[4+2]环化反应合成桥环并氮杂糖衍生物,化合物可以很好的进行保护基的脱除,为后续的活性测试提供了潜在的可能。更多还原

【Abstract】 Due to their high reaction efficiency and the ability to construct complex molecular structures,especially for the synthesis of fused nitrogen heterocycles,multicomponent reactions have become a significant area of research interest.[4+2] cycloaddition reaction is an effective method for constructing six-membered rings,so it has a wide range of applications in the chemical synthesis and biosynthesis of complex natural products and chiral drugs.Iminosuger,also known as azella sugars,are a class of nitrogenous carbohydrates with important biological activities,and are often used as glycosidase inhibitors,and have a wide range of application prospects in the field of medicine.At present,there are various methods for constructing complex nitrogen-containing heterocyclic molecules,but the methods for synthesizing fused multicyclic iminosugars are very limited.Therefore,in this paper,the common cyclization reaction is mainly used to construct the synthesis of fused multicyclic iminosugars with novel structure,which provides a basis for the development and application of such compounds.The first part of this paper uses D-ribose as raw material,and is activated by propionyl protection and p-toluenesulfonylation(Ts).At room temperature,it forms an amino ion intermediate with aniline,and then synthesizes a fused multicyclic iminosugars derivative of the [4+2] type with vinyl ether through the aza-Diels-Alder reaction.At the same time,iminosugars carboside derivatives were synthesized by the Mannich reaction.Under the heating condition of 60 °C,iminocation can be transformed into an enamine intermediate in situ,and then the imine formed with aniline and vinyl ether is formed by aza-Diels-Alder reaction to form [4+2] type of fused multicyclic iminosugars derivatives.Finally,these compounds can be well removed from the protective group.The second part of this paper uses D-ribose as raw material,which is activated by propionyl protection and p-toluenesulfonylation(Ts).Under heating conditions of 80 ℃,it forms an enamine intermediate with aniline,and then undergoes a [4+2] cyclization reaction to synthesize bridged polycyclic iminosugars derivatives with the enol structure of cyclohexenone(cyclopentenone/cyclohexenone).The compounds can be well removed from the protecting group,which provides a potential possibility for subsequent activity testing.更多还原