Studies On The Synthesis Of Diterpenoid Alkaloids Vilmorine B And Vilmorine C

Diterpenoid alkaloids were isolated from plants of the Aconitum,Delphinium,and Consolida.Diterpenoid alkaloids with structural diversity and biological significance（e.g.,selective inhibition of K⁺channels and antiarrhythmic effect）have been stimulating an increasing interest in synthetic communities.Among the diterpenoid alkaloids reported previously,vilmorine B and vilmorine C with highly rigid unique cyclopropane core consist of a new type of C₁₉-vilmoraconitine alkaloids.Based on the efficient construction of the 6/6/6 tricyclic building block and azabicyclo[3.3.1]nonane fragment,two convergent synthetic tactics have been designed to forge the structural skeleton of vilmorine B and vilmorine C.Three following chapters are included in this thesis:Chapter Ⅰ:The isolation,structural classification,biological activities,and biogenesis of diterpenoid alkaloids are presented.Advances towards the synthesis of diterpenoid alkaloids are described firstly in the second part,and then the total synthesis of C₁₈-and C₁₉-diterpenoid alkaloids in the last ten years are summarized in detail.Chapter Ⅱ:Aiming at the construction of the 6/6/6 tricyclic skeleton of diterpene alkaloids vilmorine B and vilmorine C,intramolecular 6πelectrocyclization and intermolecular Diels-Alder cycloaddition have been introduced as key reactions into our retrosynthetic analysis.The synthesis of the key precursors has been achieved,and various reaction conditions were also examined to explore the feasibility of the key transformations.Chapter Ⅲ:In order to construct the azabicyclo[3.3.1]nonane framework of diterpene alkaloids vilmorine B and vilmorine C,we design a tandem Michael addition/aldol reaction of acrolein and piperidin-4-one derivatives,which could be prepared through intermolecular double aza-Michael addition and subsequent Dieckmann condensation.And the reactivity of this azabicyclo[3.3.1]nonane synthon has been investigated preliminarily.