Studies On The Asymmetry Total Synthesis Of Natural Products: Perophoramidine,Psychotrimine, (Iso)rhynchophylline And Strychnofoline

Natural products chemistry is an important part of organic chemistry,and it’s research achievement is critical to demonstrate the level of organic chemistry. The asymmetric total synthesis of complex natural products is an important indicator of the level of organic chemistry. In this dissertation, we have developed a series of catalytic asymmetric reactions providing the key chiral stereocenters of natural products, such as Perophoramidine, Psychotrimine, (Iso)rhynchophylline and Strychnofoline. And furthermore, we have finished the total synthesis of(+)-Perophoramidine, formal synthesis of (+)-Psychotrimine and (Iso)rhynchophylline,and also constructed the key chiral spiral tetracyclic oxindole skeleton of Strychnofoline. This dissertation includes five sections:Chapter 1: Introduction to natural products of Perophoramidine and Communesins.The isolation and synthetic background of Perophoramidine and Communesins were introduced in details.Chapter 2: Construction of vicinal all-carbon quaternary stereocenters by catalytic asymmetric alkylation reaction of 3-bromooxindoles with 3-substituted indoles: total synthesis of (+)-Perophoramidine.Introduction to the asymmetric reaction of 3-halooxindole. We disclosed the first asymmetric alkylation reaction of 3-bromooxindoles with 3-substituted indoles with high diatereoselectivity and excellent enantioselectivity by using a nickel(Ⅱ) catalyst.The reaction features a catalytic asymmetric construction of highly congested vicinal all-carbon quaternary stereocenters, which is a daunting challenge in modern organic synthesis; We found that the enantioselectivity was controlled by the chiral eletrophile(indol-2-one) complex induced by chiral a nickel(II) catalyst, which are different from previous study; This methodology facilitated the asymmetric formal synthesis of(+)-Perophoramidine in a highly efficient manner.Chapter 3: Catalytic asymmetric amination reaction of 3-bromooxindoles with indolines: convenient formal synthesis of (+)-Psychotrimine.The isolation and synthetic background of Psychotrimine were introduced briefly.We disclosed the first asymmetric amination reaction of 3-bromooxindoles with indolines with high yield and excellent enantioselectivity by using a nickel(Ⅱ) catalyst,the reaction features a catalytic asymmetric construction of the N1-C3 linkage quaternary stereocenters. This methodology facilitated the first catalytic asymmetric formal synthesis of (+)-Psychotrimine in a highly efficient manner.Chapter 4: Studies on the enantioselective synthesis of Rhynchophylline、Isorhynchophylline and Strychnofoline.The isolation and synthetic background of Rhynchophylline, Isorhynchophylline and Strychnofoline were introduced briefly. We described an organocatalyzed asymmetric Michael addition reaction,and an efficient diastereoselective intramolecular iminium ion spirocyclization/lactamization cascade sequence for the construction of the key spiral tetracyclic framework, and its application to the first asymmetric total synthesis of the alkaloids Isorhynchophylline and Rhynchophylline.And also constructed the key chiral spiral tetracyclic oxindole skeleton of Strychnofoline.Chapter 5: the brief summary of our works and the prospect in this research field.