Study On The Synthesis Of Alkaloid Yuzurine From Phoebe Phoenix

Daphniphyllum alkaloids are the main active ingredients of daphniphyllaceae plants,which have very important medicinal value.They are commonly used in Chinese medicine to treat tonsillitis,snake bites,fractures and fever.The separation and total synthesis of daphniphyllum alkaloids have attracted wide attention in the area of organic chemistry due to their structural diversity and strong biological activity.Yuzurine-type alkaloids were separated from the bark and leaves of daphniphyllaceae plants,which had certain anti-cancer activity.Yuzurine is a complex and unique alkaloid with six chiral centers and two quaternary carbon centers.It consists of 5/5/6/6/7 five cycles and is the first alkaloid with piperidine spiro tetrahydropyran structure discovered up to present.Therefore,the synthesis of yuzurine molecule is a tough challenge.So far there has been no related report of its total synthesis.The unique structural characteristics and potential pharmacological effects of yuzurine have attracted us to study its synthesis.Through the synthetic routes without controlling the stereo configuration of chiral carbon,the following experiments were made:Synthesis of 3,4,5-trisubstituted piperidine ring was attempted via tandem N-alkylation-SN2' reaction.Synthesis of 3,4,5-trisubstituted piperidine ring was completed via intramolecular SN2' reaction.Construction of C-3 and C-4 quaternary carbon centers of piperidine ring and construction of seven-membered ring via HWE reaction were attempted.Through the synthetic routes with controlling the stereo configuration of chiral center,the following experiments were made:Synthesis of the yuzurine's A ring was realized via intramolecular SN2' reaction.Functionalization of side chains of 3,4,5-trisubstituted piperidine ring and construction of quaternary carbon centers were attempted.Synthesis of 3,4,5-trisubstituted piperidine ring was attempted via intramolecular SN2' reaction after protecting hydroxyl groups.The main achievements are as follows:Through the synthetic routes without controlling the stereo configuration of chiral center,synthesis of 3,4,5-trisubstituted piperidine ring was successfully achieved via intramolecular SN2' reaction using y-butyrolactone as starting material.A simple and efficient synthesis method was developed to synthesize the A ring of yuzurine molecule.The final products were racemates.On the basis of the above synthetic routes,the synthesis of yuzurine's A ring was successfully completed via intramolecular SN2'reaction,which laid the foundation for the total synthesis of yuzurine molecule.