Studies On Syntheses Of Monoterpene Indole Alkaloid Winchinine B And Aspidofractinine

The important monoterpene indole alkaloids aspidosperma and kopsia families have been studied for more than half a century owing to their intricate structures and broad biological activities.Therefore,numerous synthetic strategies have been developed for syntheses of these complex alkaloids.Now,developing an efficient strategy to approach aspidosperma and kopsia alkaloids still invites great interest.In this thesis,a new synthetic strategy has been developed,and the total syntheses of aspidosperma alkaloids(+)-winchinine B,vincadifformine,and quebrachamine had been achieved.Moreover,the pentacyclic framework of kopsia alkaloids aspidofractinine and kopsinine was constructed.The thesis includes the following three chapters:Chapter 1 Application of Indole Dearomatization Strategy in Natural Product Synthesis(review).The indole dearomatization strategy can be used to construct several chemical bonds in the skeleton of indole alkaloids,so this strategy is widely adopted to complete the syntheses of indole alkaloids.This chapter introduces the application of the indole dearomatization strategy in the syntheses of natural products,lists a large number of examples of synthetic applications,and gives a perspective on the development direction of the strategy.Chapter 2 Studies on Total Syntheses of Winchinine B,Vincadifformine,and Quebrachamine.This chapter briefly introduces the structural characteristics and syntheses of aspidosperma indole alkaloids.Synthetic research was carried out for the synthesis of(+)-winchinine B,vincadifformine,and quebrachamine.Starting from commercially available materials,the quaternary carbon chiral center was constructed by an asymmetric Michael addition,and a new synthesis strategy which included an efficient aza-Michael addition,a ruthenium-catalyzed dehydrogenation,and a palladium-catalyzed oxidative coupling was developed to install the [6,5,6] tricyclic framework of aspidosperma alkaloids.The total synthesis of(+)-winchinine B,vincadifformine,and quebrachamine were completed in 12 steps,and(+)-winchinine B was achieved for the first time.Chapter 3 Studies on Syntheses of Aspidofractinine and KopsinineThis chapter introduces structures and syntheses of aspidofranctine type kopsia alkaloids.Synthetic research was carried out for syntheses of aspidofractinine and kopsinine.The pentacyclic framework was constructed mainly through a one-pot process involving carbonyl reduction/iminium formation/intramolecular conjugate addition,and an intramolecular alkylation.The key radical cyclization and aza-Prins reaction had been attempted,which provided useful experience.