Studies On Total Synthesis Of Lycopodium Alkaloids Palhinine A And Palhinine D

In this thesis,Lycopodium alkaloids palhinine A and palhinine D are selected as our target molecules for synthesis design,wherein how to effectively construct the azonane ring system embedded in the isotwistane framework constitutes a synthetically challenging issue.Based on the disconnective and connective transform of chemical bonds,a series of enlightening strategies have been designed and put into practice,which resulted in the achievement of the first total synthesis of palhinines A,D and their C-3 epimers via the application of auxiliary ring construction/deconstructioin strategy characterized with the intramolecular nitrone-alkene [3+2] cycloaddition and subsequent reductive cleavage of the N-O bond.This thesis consists of the following three parts.Chapter 1: Retrospection of the existing research progress towards total synthesis of palhinine-type Lycopodium alkaloids.Chapters 2-3: Direct ring construction strategies(N-substitution in chapter 2 and ring-closing metathesis in chapter 3)to build the synthetically challenging azonane ring.Chapters 4-12: Auxiliary ring construction/deconstruction(ARCD)strategies for indirect introduction of the nine-membered azonane ring.That is,definitional description of the ARCD strategy in chapter 4,construction of the auxiliary bicyclo[4.3.1]decane ring system/chemoselective scission of the C?N bond in chapter 5,azidoketol fragmentation reaction in chapter 6,review of the intramolecular nitrone?alkene cycloaddition in chapter 7 and its application in construction of the auxiliary bicyclo[5.2.1]decane ring system embedded in the isotwistane framework of palhinine-type Lycopodium alkaloids in chapter 8.Divergent total synthesis of 3-epi-palhinine A(chapter 9),palhinine A(chapter 10),3-epi-palhinine D(chapter 11)and palhinine D(chapter 12).Taken together,our ARCD strategy has not only chemically demonstrated an elegant route for the first total synthesis of palhinines A and D,which provides a reliable reference for late-stage scalable synthetic design of these alkaloids aimed at further bioactive investigation,but also tactically exhibited the efficiency of the auxiliary ring construction/deconstruction approach to assembling the medium-sized ring in some conformationally rigid and sterically congested polycyclic system.