Total Syntheses Of Indoxamycins A-F And Highly Oxidized Ent-kaurane Diterpenoids Through Tandem Reactions

This dissertation focuses mainly on the asymmetric total syntheses of indoxamycin family and ent-kaurane diterpenoids including pharicin A,pharicinin B,7-0-acetylpseurata C and pseurata C.Selfdesigned tandem reactions were set as the key steps and highlights in both approaches.The dissertation consisted of two parts as follow:Chapter 1:Asymmetric Total Syntheses of Indoxamycins A-FIndoxamycins A-F represent a novel class of polyketides isolated from the salin cultures of actinomycetes,which contain a common sterically congested[5,5,6]tricyclic cage-like structure featuring six contiguous stereogenic centers.This chapter summarizes the synthetic progress towards indoxamycin family both by the Carreira and Sorensen groups before fully intriducing our works.We have developed a concise and stereoselective approach for the divergent total synthesis of(-)-indoxamycins A-F in 16-21 steps.The salient features of our strategy entail an Ireland-Claisen rearrangement,a palladium catalyzed enantioselective 1,6-enyne reductive cyclization,and a tandem 1,2-addition/oxa-Michael/methylenation reaction.The described synthesis unambiguously determined the relative and absolute configuration of these natural products,and also enabled their preliminary biological investigations.Chapter 2:Asymmetric Total Syntheses of highly oxidized ent-Kaurane Diterpenoids Pharicin A,pharicinin B,7-O-acetylpseurata C and pseurata C represent a classic class of ent-kauranoids isolated from Isodon genus,which contain a highly oxygenated bicyclo[3.2.1]octane framework featuring eight or nine stereogenic centers.Pharicin A is capable of perturbing mitotic progression and initiating mitotic catastrophe,which merits further preclinical and clinical investigations for cancer drug development.After fully reviewing previous achievements in total syntheses of ent-kaurane diterpenoids,we developed an unprecedented oxidative dearomatization-induced[5+2]cycloaddition/pinacol-type 1,2-acyl migration cascade for directly constructing the highly oxygenated bicyclo[3.2.1]octane core structure of ent-kaurane diterpenoids.Taken together with a retro-aldol/aldol process and a singlet oxygen ene reaction,the employment of this concise and convergent approach for assembling the highly oxidized ent-kauranoids is demonstrated by the first asymmetric total syntheses of pharicin A,pharicinin B,7-O-acetylpseurata C and pseurata C.