Synthesis Of The AE Ring System Of The Alkaloid Yuzurine Of Phoebe Phoenix

Yuzurine is a kind of terpene alkaloids,which was first isolated from roots and leaves of D.macropodum and D.gracile in 1974.Yuzurine possess moderate antitumor activity,and its structure is novel and unique.Its structure composed of five rings,including a unique hexagonal cyclic ether which is not found in other types of alkaloids.Despite of the skeleton of yuzurine is dazzling and has a considerable value in drug discovery;its synthesis study has not been reported so far,probably due to the challenge complex structure.China has abundant resources of Daphniphyllum.The study on the synthesis of yuzurine will help us further discover,excavate and study the treasures in Chinese traditional medicine,so as to benefit human health.In this thesis,we carried out the synthesis study of yuzurine.The yuzurine AE bicyclic system was constructed quickly and efficiently with the overall yield of 7%in 10 steps from the commericially available starting material sarcosine methylestes hydrochloride.This study laid a solid foundation for the total synthesis of yuzurine.The success of this synthesis depends on three key steps:(1)A Dieckmann ester condensation reaction was used to construct the tri-substituted piperidine ring A.(2)The unique lactone backbone was employed to control the diastereoselectivity of formation of the C-4 and C-5 chiral centers.(3)An acid-catalyzed cyclization of dihydroxyl with ketal was employed to construct the rine E.