【作者】 王磊；

【导师】 徐显秀；

【作者基本信息】 山东师范大学 ， 有机化学， 2021， 硕士

【摘要】 杂环结构广泛存在于天然产物和生物活性分子中,在医药和农药领域有着十分重要的地位。此外,杂环化合物也是重要的有机合成中间体,广泛用于有机化学、材料化学、药物化学等领域。其中,双苯并吡喃是albanol A,sorocenol E和australisin A等天然产物的母核结构,此类天然产物显示出抗癌、抗疟、植物毒性、促红细胞生成素基因表达和乙酰胆碱酯酶抑制的作用等广泛而多样的生物学活性。因此,开发双苯并吡喃类化合物的合成新方法备受关注。异氰基乙酸酯是一类常用的有机合成子。基于异氰基乙酸酯的环加成反应通常是合成噁唑、咪唑等五元杂环的有效方法。并且,在此类反应中,异氰基乙酸酯的酯基通常仅作为活化基团、杂环产物的取代基而未参与反应。并且,所生成的杂环产物多为五元简单杂环,更加复杂的桥环体系的却鲜有报道。然而,运用异氰基乙酸酯的串联杂环化反应高效合成结构复杂且重要的多环化合物却有重要的实际意义。本论文发展了异氰基乙酸酯与原位产生的邻亚甲基醌的串联杂环化新反应,为非对映发散性合成二氢噁唑并双苯并吡喃化合物提供了高效新方法。该反应从简单易得的原料出发,可通过变化反应条件调控反应的非对映选择性,高步骤经济性和非对映选择性地构筑两种含有五个环的二氢噁唑并双苯并吡喃化合物非对映异构体。并且,该反应中异氰基乙酸酯的酯基既作为活化基又作为反应基团,参与了产物母核结构的构筑,提高了产物结构的复杂性,为合成具有新型结构的杂环骨架提供了高效实用的方法。在此基础上,本论文研究了异氰基乙酸酯与邻亚甲基醌的对映选择性串联杂环化反应,发展了以中等的对映选择性合成二氢噁唑并双苯并吡喃化合物的方法。更多还原

【Abstract】 Heterocyclic structures are widely found in natural products and biologically active molecules,and have a very important position in the fields of medicine and pesticides.In addition,heterocyclic compounds are also important organic synthesis intermediates,which are widely used in organic chemistry,materials chemistry,medicinal chemistry and other fields.Among them,bisbenzopyran is the core structure of natural products such as albanol A,sorocenol E and australisin A.Such natural products show anti-cancer,anti-malarial,phytotoxicity,erythropoietin gene expression and acetylcholinesterase inhibition as well as other broad and diverse biological activities.Therefore,the development of new synthetic methods for bisbenzopyrans has attracted much attention.Isocyanoacetates are versatile organic synthons.Cycloaddition reaction based on isocyanoacetate is usually an effective method to synthesize simple five-membered heterocycles such as oxazole and imidazole.In addition,in this type of reaction,the ester group of isocyanoacetate usually only serves as an activating group and a substituent of the heterocyclic product without participating in the reaction.However,there are few reports on the efficient synthesis of complex and important polycyclic compounds using the tandem heterocyclization of isocyanoacetate.In this thesis,a diastereodivergent tandem heterocyclic reaction between isocyanoacetate and o-methylenequinone(produced in situ)is developed,which provides a highly efficient novel proptocol for the diastereoselective synthesis of dihydrooxazolobisbenzopyran derivatives.The reaction starts from simple and readily available raw materials,the diastereoselectivity of the reaction can be adjusted by changing the reaction conditions.A variety of bridged compounds can be constructed in a one-step domino transformation.In addition,the ester group of the isocyanoacetate serves as both an activating group and a reactive group in this reaction,which increases the complexity of the product structure and improves the reaction efficiency.更多还原