Study On The Total Synthesis Of Monoterpene Indole-alkaloid(-)-tabersonine

Tabersonine is one of the monoterpene indole alkaloids of the Aspidosperma class,which include over 250 unique members.Tabersonine was isolated from Amsonia tabernaemontana in 1954 by Le Men.It has been found to play a critical role in the biosynthesis of Catharanthine,Vindoline and Vincamine.Catharanthine and Vindoline are precursors for the synthesis dimeric alkaloids vinblastine(VLB)and vincristine(VCR).Vinblastine indole alkaloids have a strong pharmacological activity,especially for cancer treatment.This thesis discussed the synthetic studies toward the synthesis of Tabersonine.This thesis consists of three chapters:In Chapter 1,the total synthesis of indole alkaloid Tabersonine was briefly reviewed.In the past few decades,The racemic synthesis and asymmetric synthesis of tabersonine had been completed in different ways.The Claisen rearrangement,intramolecular Diels-Adel reaction,free radical reaction,Heck reaction,and Domino Michael/Mannich/N Alkylation reactions have been used in the synthetic routes.In Chapter 2,the total synthesis of(-)-tabersonine was investigated,Condensation of indolyl aldehyde and(S)-tert-Butanesulfinamide provided N-tert-butanesulfinylimine.A highly selective 1,2-addition of organolithium regents towards sulfinyl imine provided sulfinyl-amide in good isolated yield.AgOTf-mediated tandem cyclization was used to create rings C and E.Then oxidative cleavage of the double bond followed by Aldol reaction construct the D ring.Subsequently,the key intermediate was obtained by dehydration and construction of the C-20 quaternary carbon center,which provided a synthelic basis for the total synthesis of(-)-Tabersonine.In Chapter 3,the experimental process and NMR data were recorded...