Structural Modification Of Alisol A/B And Total Synthesis Of Lycopodium Alkaloids Huperserratines A/B

This thesis consists of three chapters.The first chapter introduces the structure modification and structure-activity relationship of alisol B;The second chapter introduces the isolation and identification of Lycopodium alkaloids from Huperzia serrata and the first total synthesis of huperserratines A and B;The third chapter reviews the research progress of total synthesis of Lycopodium alkaloids in the past five years.Chapter 1 Structural modification and structure-activity relationship of alisol BNon-alcoholic fatty liver disease(NAFLD)is a disease characterized by hepatic steatosis and excessive accumulation of hepatic fat except other definite factors such as alcohol,drugs,and genetic diseases.In China,the prevalence of NAFLD in adults is about 30%,while the prevalence in obese and diabetic groups can reach 70%.NAFLD has become a public health problem that threatens global health.The pathogenesis of NAFLD involves many factors and is a complex process.Therefore,effective treatment methods are very limited.At present,dietary intervention and exercise therapy are mainly used to prevent and treat fatty liver in clinical practice,and there is no specific drug for NAFLD.Alisma orientalis is traditional Chinese medicine,and the protostane triterpenes are unique to this genus.A large number of studies have found that the extracts of Alisma orientalis and the active components of triterpenes have the activity of treating NAFLD.Starting from alisol B,the main component of Alisma orientalis,we designed and synthesized 62 derivatives,and screened 7 derivatives with better activity through the NAFLD activity screening model,and carried out animal experiments on some derivatives.Through the research on structural modification and structure-activity relationship of alisol B,modification methods of each functional group and the activity of treating NAFLD have been preliminarily proved,which has laid a solid foundation for the further development of alisol B with high content in Alisma orientalis.Chapter 2 Chemical constitiuents and total synthesis of lycopodium alkaloidsLycopodium alkaloids huperserratines A and B are a pair of isomers isolated by our research group from Huperzia serrata(Thunb.)Trev.in 2020 and the first example of macrocyclic Lycopodium alkaloids with bicyclo[10.4.0]hexadecane skeleton and a rare oxime functional group.We re-studied the chemical constitiuents of Huperzia serrata,and successfully obtained huperserratines A and B and 7 other compounds,including 5 new compounds.Since these two compounds are less in the plant,in order to facilitate their continued research and development,we started from the known compound(5R)-2-Iodo-5-methyl-2-cyclohexen-1-one,and formed the key bicyclo[10.4.0] hexadecane skeleton through key reactions such as Suzuki-Miyaura coupling,Michael addition,and ring-closing metathesis.Then,the total synthesis of the target molecules huperserratines A and B was completed for the first time through a total of 12 steps through double hydroxylation,Swern oxidation,and oxime formation reaction.The first synthesis work not only lays the foundation for further research work on these two novel compounds but also opens up new ideas for the synthesis of lycopodine,fawcettimine,and other Lycopodium alkaloids.Chapter 3 Research Progress on Total Synthesis of Lycopodium AlkaloidsThis chapter reviews the research progress of total synthesis of Lycopodium alkaloids in the past five years.It is hoped that it can provide some reference for the total synthesis of Lycopodium alkaloids.