Effective Preparation of Valuable Biologically Active Compounds Employing Catalytic Construction of Polycyclic Ring System

当多环骨架上存在多种官能团时，官能团之间的三维关系受到限制，并且由于刚性构象而产生特定的生物活性。因此，迫切需要开发一种高效的多环体系构建方法，特别是在药物化学领域。级联反应是构建多环骨架的有效方法，多环骨架是生物活性的重要核心。研究了在多种反应条件下进行的各种级联反应，如周环、极性、自由基和过渡金属催化的反应条件。通过分子内双Michael反应合成了Culmorin、戊烯、戊烯酸、脱氧戊烯酸、长冰片、雪松二醇、8,14 -雪松氧化物、atisirene、atisine和甾类类固醇。采用Aza双Michael反应合成了tylophorine、epilupinine、tacamonine和paroxetine。此外，连续的Michael和aldol反应在分子内和分子间进行，导致形成融合成四元环的多环化合物。利用多组分级联反应合成paesslerin A揭示了所提出的结构中的一个错误。还研究了在自由基和过渡金属催化条件下进行的独特级联反应。通过多种级联反应，选择性合成了具有神经保护作用的血清芬地酸和甲基7β-羟基钙酸甲酯。

When various functional groups exist on a polycyclic skeleton, the three-dimensional relationships of the functional groups are restricted and a specific biological activity would be expected due to the rigid conformation. Therefore, the development of an efficient method for the construction of polycyclic ring systems is highly desired, particularly in the field of medicinal chemistry.Cascade reactions are useful methods for the construction of polycyclic skeletons, which are important cores for biological activities. A variety of cascade reactions, carried out under multiple reaction conditions, such as pericyclic, polar, radical, and transition metal-catalyzed reaction conditions, have been investigated.Culmorin, pentalenene, pentalenic acid, deoxypentalenic acid, longiborneol, cedrandiol, 8, 14-cedranoxide, atisirene, atisine, and estrane-type steroids were synthesized via the intramolecular double Michael reaction. Aza double Michael reaction was applied to the syntheses of tylophorine, epilupinine, tacamonine, and paroxetine. Furthermore, sequential Michael and aldol reactions were performed in both intramolecular and intermolecular manners, leading to the formation of polycyclic compounds fused to a four-membered ring. Synthesis of paesslerin A utilizing a multicomponent cascade reaction revealed an error in the proposed structure.Unique cascade reactions, performed under radical and transition metal-catalyzed reaction conditions, were also investigated. With the combination of several cascade reactions, serofendic acids and methyl 7β-hydroxykaurenoate, both of which have neuroprotective activity, were synthesized in a selective manner.