Multicomponent/cascade cyclization strategies (MCCS) for the synthesis of bioactive natural products and analogues

This thesis describes the application of multicomponent/cascade cyclization strategies (MCCS) for the synthesis of bioactive natural products and the main scaffolds exist in natural products. The research is based on the A3 coupling, and post-Ugi reactions developed previously in our laboratory.

Chapter 1 gives an introduction to multicomponent reactions and cascade reactions. Giving the conception of the MCCS and highlighting the advantages of MCCS for the synthesis of natural products and drugs. The examples MCCS for the synthesis of natural products will be discussed. The goals of this thesis are also summarized in this chapter.

Chapter 2 describes the A3-coupling and guanylation reaction as tools for the preparation of propargylguanidine. The propargylguanidine was triggered by phenyliodonium diacetate (PIDA) for a cascade cyclization. The difference in the electronic nature of the acetylene substituent resulted in two ways of the cyclization. Total synthesis of Kealiinines B and C in a concise way were realized.

Chapter 3 describes gold-catalyzed tandem hydroamination/cycloisomerization of Ugi adducts, N-alkynic or N-cyano propiolamides tactic for the synthesis of highly functionalized N-heterocyclic 1,6-annulated 2-pyridones and 2-pyrimidinones scaffolds. This novel high-efficiency method allows the rapid construction of these diverse N-heterocyclic scaffolds from readily available starting materials with wide substrate scopes and good functional group tolerance. Total synthesis of (±)-seco-antofine and (±)-septicine were realized with this cascade reaction.

Chapter 4 describes an expeditious synthetic strategy to access diverse (spiro)polyheterocycles from easily available starting materials in two operational steps including an Ugi four-component reaction and a cationic gold(I)- catalyzed cascade bicyclization. Divergent synthesis of these structurally complex pyrido[2,1-a]isoindol-4(6H)-ones and spiroisoquinoline-pyrrole-3,5′-diones via a cascade nucleophilic cyclization/intramolecular 1,3-migration/1,5-enyne cycloisomerization process and a tandem hydroamination/ Michael addition sequence, respectively, was controlled by substituents, where the electronic effect on the migrating groups and steric effect of the secondary amide moieties play crucial roles.

Chapter 5 is the data for the compounds. The H1 NMR and C13 NMR,  High-resolution mass spectrometry (HRMS) and the information of the crystal.

 Finally, General conclusions and perspectives are highlighted.