【作者】 王海军；

【导师】 吴祥；

【作者基本信息】 合肥工业大学 ， 化学工程与技术， 2019， 硕士

【摘要】 托品烷骨架已被公认为“特权骨架”,许多天然生物活性产品和药物都含有此类结构,且许多托品烷衍生物在免疫、神经和精神疾病等方面发挥着至关重要的作用;在许多用于治疗糖尿病和抗肿瘤候选药物的先导化合物和药物中也含有苯环结构的苯并托品烷。托品烷衍生物的生物活性已经激发了合成化学家的广泛兴趣,并且已经开发出几种催化方法用于构建光学纯的托品烷骨架。但总得来说,文献报道相对较少。因此,开发出一种新颖、绿色、简便的方法合成托品烷,尤其是具有光学活性的托品烷具有非常重大的意义。本文开发了一种Pd/C催化的串联反应用于合成苯并托品烷的方法。该反应通过Pd/C催化发生脱氢作用形成甲亚胺叶立德,进而与硝基苯乙烯衍生物发生1,3-偶极环加成反应。在温和的条件下反应并以良好的收率产生结构复杂的苯并托品烷,且具有优异的非对映选择性。不对称反应的初步结果表明,铜催化剂和手性单亚磷酰胺配体可以得到具有中等ee的光学活性产物。更多还原

【Abstract】 The tropane skeleton has already been recognized as a “privileged scaffold” in a great many natural bioactive products and pharmaceuticals.Many tropane derivatives play pivotal roles in a myriad of immune,neurological and psychiatric diseases.Benzotropane,containing a phenyl ring in the tropane moiety,also occurs in numerous lead compounds and pharmaceuticals for the treatment of diabetes and antitumor drug candidates.The medicinal relevance of tropane derivatives has stimulated considerable interest among synthetic chemists,and several catalytic methods have been developed for the construction of optically pure tropane frameworks,but in general,there are only a few cases of related reports.Therefore,the development of a novel,green,and simple method for the synthesis of tropane,especially for the optically active tropane,is of great significance.A Pd/C-catalyzed cascade approach for the synthesis of attractive benzo-fused tropanes was developed.The reaction proceeds through a sequential Pd/C-catalyzed dehydrogenative formation of azomethine ylides from amines and 1,3-dipolar cycloaddition.It allows the generation of structurally complex benzo-fused tropanes in good yields with excellent diastereoselectivities under mild reaction conditions.Preliminary results of asymmetric version of the reaction reveal that the copper catalyst and chiral monophosphoramidite ligand can furnish optically active products with moderate ee.更多还原