Studies On The Asymmetric Total Synthesis Of Hexahydropyrroloindole Akaloids(+)-chimonanthine,(-)-ditryptophenaline And(+)-nocardioazine B

The hexahydropyrrolo[2,3-b]indole,commonly referred to as the pyrroloindoline,is a common heterocyclic motif that unites several structurally diverse and biosynthetically distinct families of alkaloids.Alkaloids possessing the pyrroloindoline framework constitute a large class of natural products isolated from plants,microorganisms and fungi.Among them,the vicinal C3a-C3a' quaternary carbon containing members are especially attractive due to their unique architecture and their interesting biological activities.Stereocontrolled synthesis of the congested all-carbon quaternary stereocenters in these alkaloids presents a formidable challenge.In this field,Overman and his team have made pioneering contribution to the syntheses of dimeric and oligomeric HPI alkaloids,and the key structure-units of dimeric HPI alkaloids were synthesized either by a double Heck cyclization of o-iodoanilide derivatives or dialkylation of bis-oxindoles.In 2007,Mavassaghi reported a reductive radical dimerization strategy for the synthesis of dimeric HPI alkaloids.Based on this reductive dimerization,a number of important studies have been published on the syntheses of dimeric HPI alkaloids.In this thesis,we report a copper catalyzed sequential arylation-oxidative dimerization reaction as the key step for the synthesis of hexahydropyrroloindole alkaloids(+)-chimonanthine,(+)-folicanthine,(-)-calycanthine and(-)-ditryptophenaline.We also do some exploratory work on the synthesis of natural products(+)-nocardioazine B.Three chapters are included in the thesis.In the first chapter,the structure of hexahydropyrroloindole alkaloids,its biosynthesis,and some important total syntheses of hexahydropyrroloindole alkaloids are summarized.In chaper 2,We have developed the first copper catalyzed arylation-oxidative dimerization of o-haloanilides with a remote assistance of an intramolecular sulfinyl amide unit.Based on this method,a general synthetic strategy has been successfully established for the total synthesis of chimonanthine,folicanthine,calycanthine and ditryptophenaline.In chaper 3,Experiment procedure,physical and spectrum data for compounds described in Chapter 2 are recorded.