Study On Divergent Total Synthesis Of Lycorine Type Active Compounds In Lycorine Radiata

There are many secondary metabolites in Chinese medicine,especially plant medicines,such as alkaloids,terpenoids,flavonoids,and saponins.These active compounds are the key factors to exert their efficacy.In this paper,in order to synthesize Lycorine type alkaloidsγ-lycorane,hippadine,anhydrolycorine,and so on,we studied the total synthesis of Lycorine type alkaloids in Amaryllidaceae by C-H functional reaction and divergent total synthesis strategy.Two methods for the synthesis of hydrogenated indole fragments 1 have been developed.The synthesis ofγ-lycorane was accomplished by two routes.In Chapter 1,the synthesis ofγ-lycorane was introduced.The commercial available1,3-cyclohexadione was used as the starting material to prepare hydrogenated indole fragments 1 by"one-pot"ozonation/reductive amination/cyclization.The synthesis ofγ-lycorane was accomplished by a photo-promoted cyclization/oxidation cascade.In Chapter 2,a palladium-catalyzed One-pot sequential C-H functionalization strategy was applied to the divergent synthesis of Lycorine type alkaloids.Inspired by the results of Chapter 1,we design divergent synthesis routes for other members of the Lycorine type alkaloids.The preparation method of hydrogenated indole fragment 1 was re-optimized,which the advanced intermediate 1 was prepared by intramolecularγ-alkylation reaction.And then in the one-pot reaction,The palladium-catalyzedα-C(sp~2)-H arylation/benzylic C-H oxidation,α-C(sp~2)-H arylation/benzylic C-H oxidation/γ-C(sp~3)-H oxidation orα-C(sp~2)-H arylation/benzylic C-H oxidation/α-C(sp~3)-H oxidation cascade was used to construct tetracyclic galanthan core.The aromatization of the key intermediate 7d was studied.Finally,the synthesis of Sceletium alkaloids was preliminarily attempted.In Chapter 3,the total synthesis of Lycorine and Sceletium alkaloids in Amaryllidaceae was reviewed.