Studies On Asymmetric Synthesis Of Hydrocarbazole Alkaloids

The alkaloids with a densely functionalized hydrocarbazole scaffold are widespread in many natural sources.Because of their high structural diversity and various biological properties,some of these alkaloids have received considerable attention from the synthetic chemists.Stimulated by recent progress in asymmetric catalysis,the asymmetric synthesis of these alkaloids has provoked great interest in synthetic community.This dissertation aims at the synthetic studies of Apocynaceae hydrocarbazole alkaloids,an unprecedented asymmetric catalytic tandem aminolysis/aza-Michael addition reaction of spirocyclic para-dienoneimides has been designed and developed through organocatalytic enantioselective desymmetrization.The present studies providing a new method for the expeditious assembly of multifunctionalized hydrocarbazole building blocks bearing the crucial all-carbon quaternary stereocenter.On the basis of this key asymmetric tandem methodology,the chiral synthesis of three Apocynaceae alkaloids,(+)-deethylibophyllidine,(+)-limaspermidine and(+)-1-acetylaspidoalbidine has been explored.Simultaneously,the total synthesis of Apocynaceae alkaloids,(-)-melotenine A containing unique seven-membered ring has been preliminarily explored.The following five parts are included in this thesis:Part ?:With the retrospective for the literature reports on the synthesis and application of hydrocarbazoles,and highlighted the catalytic enantioselective synthestic methods.Part ?:Focusing on the assembly of hydrocarbazole building blocks bearing the crucial all-carbon quaternary stereocenter,and combining the reports on enantioselective desymmetrization of para-dienone,details the asymmetric catalytic tandem aminolysis/aza-Michael addition reaction we have developed.Part ?&?:On the basis of the asymmetric tandem methodology developed in Part ?,we has divergently explored the total synthesis of(+)-limaspermidine,(+)-1-acetylaspidoalbidine and(+)-deethylibophyllidine.Part ?:For further expand the application of the asymmetric tandem methodology,based on the common intermediate,the synthesis of(-)-melotenine A with unique seven-membered ring containing conjugated double bonds has been preliminarily explored.Though the total synthesis of(-)-melotenine A is under way in our research group,the present studies will provide the basis for the synthesis of related alkaloids.