Synthetic Studiy On The Daphniphyllum Alkaloid Daphnezomine B

This thesis is to carry out a total synthesis study on Daphnezomine B of Daphnezomine-type Daphniphyllum alkaloids,and complete the construction of ABCD tetracyclic skeleton with its lactone ring.Synthesis of natural products can provide new lead compounds,synthesis methods,strategies,inspirations and tool molecules for new medicine research and development.In the 1970 s,professor Heathcock proposed the biogenic synthesis pathway of Daphniphyllum alkaloid,which opened the way for the total synthesis of Daphniphyllum alkaloids.The Daphniphyllum alkaloids has antitumor,antiviral,insecticidal,vasodilator and other biological activities.In this thesis,the unsynthesized Daphniphyllum alkaloid molecule Daphnezomine B was selected as the research target.In this thesis,based on AB dicyclic compound 195,the aza Michael addition reaction successfully constructed the C ring of Daphnezomine B,and realized the synthesis of ABC tricyclic intermediate in gram scale.After the ABC tricyclic intermediate was obtained,the oxidation state of A ring was firstly adjusted,and then an amide side chain was introduced into B ring by Suzuki coupling reaction.The tetracyclic skeleton of Daphnezomine B was obtained by the efficient construction of D ring through amideactivated annulation reaction.After the failure of the design to construct lactone ring by using Michael addition reaction,theoretical analysis was carried out,through a pot series oxidation reaction and SN2? reaction is concise and efficient implementation in the construction of the lactone ring.On the basis of known intermediates,the synthesis of ABCD tetracyclic skeleton and its lactone ring of Daphnezomine B was completed in a brief nine-step linear step,which laid a foundation for the total synthesis of Daphnezomine B.