Synthetic Study On Sesterterpene Aleurodiscal

Natural products play an indispensable role in the development of human society,especially in the treatment of diseases by providing a large number of medicinally important molecules.Due to the complex structure of natural products,the total synthesis of natural products is also known as the "Holy Grail" in organic synthesis.Sesterterpenes are a small branch of natural products,which exhibit diverse important biologic properties such as anticancer,antitumor,antibacterial,antifeedant and immunosuppression.The combination of complicated architectures and impressive pharmacological properties of sesterterpenes has been attracting increasing interest from the synthetic community over these years.Aleurodiscal is a sesterterpene with antifungal activity,which was isolated from mycelial cultures of Aleurodiscus mirabilis(Berk.& Curt.)H?hn that were collected from Japanese camphor bark.Although over 30 years has passed after its isolation,there is no reported total synthesis of Aleurodiscal.Structurally,Aleurodiscal has a unique trans-isopropyl hexahydroindane motif and an intimidating eight-membered ring.Therefore,it has greatly attracted our interest.We selected Aleurodiscal as our target molecule and hope to improve the synthesis efficiency through convergent strategy.Within this dissertation,it was envisioned that Aleurodiscal can be accessed by combining two fragments,namely trans-isopropyl hexahydroindane and alkenyl bromide.Within the trans-isopropyl hexahydroindane fragment,we carried out a sequence of Michael addition,Aldol condensation,and aluminum-catalyzed cationic cyclization to construct the 5/6 fused bicyclic system.Subsequently,we adjusted the configuration of the hydroxyl group to direct the following hydrogenation to provide a trans-bicyclononane.After homologation,further modifications including a typical oxyCope rearrangement,we finished the synthesis of trans-isopropyl hexahydroindane segment in 11 steps.As to the alkenyl bromide fragment,9 steps transformation that includes a microwave mediated rearrangement,enzyme catalyzed desymmetric hydrolyzation,hydroxyl protection,stereoselective Michael addition,and nickelcatalyzed bromination was applied to fulfill the task.All reactions were carried out in multi-gram scale,providing a solid basis for subsequent synthesis.