Study On Asymmetric Total Synthesis Of Catharanthine

Catharanthine is an Iboga alkaloid isolated from the leaves of Madagascar periwinkle,which accounts for only 0.0003%of the dry leaf weight.Being used as a chemical synthesis precursor for the anticancer natural products vinblastine and vincristine,catharanthine can also be utilized for the industrial production of the anticancer drugs vinorelbine and vinflunine.Catharanthine has a typical aza-heterobicyclic-[2.2.2]-octane structure,which contains three chiral centers,one of which is an all carbon quaternary center.Because of its huge industrial production prospects and complex chemical structure,catharanthine has been regarded as a hot topic and focus in the field of total synthesis of natural products by synthetic chemists.To date,a series of total synthesis of catharanthinea have been reported by many research groups.In this thesis,the asymmetric synthetic strategy of catharanthine based on chiral tert-butylsulfonamide resolution has been reported.This thesis is divided into three chapters.The first chapter summarizes the research progress for the synthesis of natural product catharanthine.The second chapter is the research content of the subject.We adopted the convergent synthesis strategy to divide catharanthine into two key synthetic fragments,and then synthesize and assemble them,aiming to realize the asymmetric synthesis of catharanthine.Using chiral tert-butyl sulfonamide as a chiral resource,the resolution of the dissymmetrized diol fragment was achieved,the synthesis of the key chiral fragments was successfully completed.Synthesis of another segment by Suzuki coupling reaction,Vilsmeier reaction and Wittig reaction was also accomplished.Our work laid a foundation for the asymmetric synthesis of catharanthine.The third chapter is experimental procedures and spectrum data for all new compounds.