Collective Syntheses Of Iboga-Type Indole Alkaloids And Synthetic Studies Toward Sesquiterpenoid Mitchellene B

This thesis is mainly focused on total syntheses of iboga-type alkaloids tabertinggine,ibogamine,ibogaine,ibogaine hydroxyindolenine,3-oxoibogaine hydroxyindolenine,iboluteine,ervaoffines D and sesquiterpenoid mitchellene B.It consists of the following three chapters: Chapter 1 Intramolecular Diels-Alder Reaction in Natural Product Synthesis(review)This review mainly describes the application of intramolecular Diels-Alder reaction(IMDA)which has played an important role in total syntheses of terpenoids,alkaloids,polyketides and other natural products by the exhibition of representative synthetic examples.Chapter 2 Synthetic Studies on Sesquiterpenoid Mitchellene BA brief introduction of the background for the isolation,structures and biological activities of mitchellene A-C is provided.In order to synthesize mitchellene B,domino intramolecular Diels-Alder reactions have been developed.Using this strategy,the 6/6/5/5 fused tetracyclic framework of mitchellene B was constructed and 4-epi-mitchellene B was also accomplished.Chapter 3 Bioinspired Collective Syntheses of Iboga-Type Indole AlkaloidsA brief introduction of the background for the isolation,structures,biological activities and synthetic developments of iboga-type indole alkaloids is given.After retrieving literature and comparing the structure of iboga alkaloids,we proposed the bioinspired collective syntheses strategy and accomplished the total syntheses of several iboga alkaloids.Studies toward tabertinggine and 12-methoxy-tabertinggine were carried out through two synthetic routs.The skeleton of tabertinggine was constructed from commercially available dimethyl-5-hydroxyisophthalate and tryptamine through Rh catalized hydrogenation,Pictet-Spengler reaction,desymmetric amidation and functional group transformations.The isomer of tabertinggine and its analogues were also synthesized.The total syntheses of tabertinggine and 12-methoxy-tabertinggine were accomplished in 10 steps with 40% overall yield,from dimethyl 2-oxoglutarate and tryptamine or 5-methoxy-tryptamine through Pictet-Spengler reaction/intramolecular ammonolysis,Aldol condensation reaction and other operations.The total syntheses of ibogamine,ibogaine,ibogaine hydroxyindolenine,3-oxoibogaine hydroxyindolenine,iboluteine and ervaoffines D were also accomplished.