Studies On Synthesis Of Mollanol A

In 2014,Yu Shi-shan research group in Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College first isolated mollanol A–a new type of grayanoids from the fruits of Rhododendron molle.This natural product is a diterpenoid with a new C-nor-D-homograyanane skeleton.It features a [5,6,5,6,5] pentacyclic ring skeleton with eight stereocenters.The all carbon[3.2.1] bridge ring system and oxa-[3.2.1] bridge ring system in this molecule make it much more challenging to synthesize.This dissertation documents a synthetic study of mollanol A,which including the following three chapters:The first chapter systematically introduced the isolation,structure identification,biological activity and biosynthesis hypothesis of mollanol A.The second chapter introduced the total synthesis of grayanoids.The third chapter mainly introduced the research progress of our research group on the synthetic studies of mollanol A,which is the main texts of this paper.In view of the unique structure of mollanol A,a convergent strategy to synthesize mollanol A was designed.Mollanol A could be constructed via Stille coupling approach,which the left-most five-membered ring fragment and the bicyclo[3.2.1] fragment on the right would be joined to assemble the core skeleton.The five-membered ring could be obtained from 2-methyl-1,3-cyclopentanedione as the starting material through a series of reactions such as CBS reduction.In addition,the bicyclo[3.2.1] fragment was accessed by Conia-ene reaction,which cyclopentanone as the starting material.Through continuous exploration and optimization,the key intermediate 3-170 was constructed finally.