Studies On The Asymmetric Synthesis Of Several Akuammiline Alkaloids

This dissertation includes three chapters: 1)synthetic developments of akuammiline alkaloids,2)studies on the asymmetric synthesis of Aspidophylline A,3)studies on the asymmetric synthesis of other related akuammiline alkaloids.In the chapter 1,the background of the akuammiline alkaloids,including their isolation,structural features,biological activities,and proposed biosynthesis was introdeced.Moreover,the synthetic developments of Vincorine,Aspidophylline A,Picrinine,Scholarisine A,and Strictamine were briefly summarized.In the chapter 2,the asymmetric synthesis of Aspidophylline A was introduced.Aspidophylline A is a complex pentacyclic compound,characterized by a aza-bridged [3,3,1] bicycle and five contiguous stereogenic centers,one of which is an all-carbon quaternary carbon.It is worth noting that all stereogenic centers come from a unique polysubstituted cyclohexyl ring.We have developed a concise stategy for the formal total synthesis of(±)-Aspidophylline A.A cationic gold(I)-catalyzed 6-endo-dig tandem cyclization reaction of alkynylindole followed by a Pd-catalyzed methoxycarbonylation have been utilized to construct the challenging tetracyclic system of Aspidophylline A.At the same time,an asymmetric total synthesis of(-)-Aspidophylline A has been accomplished.The key transformations include: 1)an asymmetric hydride transfer hydrogenation in which the newly formed stereocenter determines all the remaining stereochemistry based upon substrate control,2)a cationic gold(I)-catalyzed 6-exo-dig cyclization involving an alkynylindole/aminal formation cascade,which enables stereoselective establishment of the requisite quaternary carbon center.3)an intramolecular azidoalkoxylation,which was utilized to construct the desired challenging tetracyclic framework of(-)-Aspidophylline A with high stereoselectivity.In the chapter 3,the asymmetric synthesis of other related akuammiline alkaloids was introduced.The investigation of applications of this cascade reaction of gold(I)to the total synthesis of other related akuammiline alkaloids is ongoing in our laboratory,and some progress has been achieved.