Studies On Skeleton Construction Of Lycorine

Amaryllidaceae alkaloids are broadly existed in lycoris radiata plants, and these kinds of alkaloids feature broad and obvious bioactivities, such as the functions of anti-AIDS, anti-acetylcholinesterase, anti-tumor activity and anti-virus functions. Up till now, more than 500 kinds of compounds have been separated, based on their structural characteristics. In general they are classified into five kinds of amaryllidaceae alkaloids.Lycorine and its derivatives belong to amaryllidaceae alkaloids, and due to its substantial bioactivities, pharmacological effects and structures of pyrrole and phenanthridine, they have caused the attention of the experts of organic synthesis and medicinal chemists for decades. In recent years, the study of lycorine and its derivatives have been focused on the research of pharmacological effects of anti-tumor, anti-virus and Alzheimer’s disease and its total synthesis. This Paper mainly fuses on the study of constructing the lycorine skeletons based on the AD→ADB→ADBC ring construction sequence synthesis strategies.There are four chapters in this paper. Chapter Ⅰ introduces the structural characteristics and the pharmacological effects of amaryllidaceae alkaloids including anti-tumor, anti-virus and anti-AD activities. It goes on to introduce the structural modification work of lycorine reported in recent years. Finally, it introduces the basic skeletons constructions with metal catalytic, Michael reaction and D-A reaction as the key reactions in recent years, as well as the total synthesis of lycorine in the different construction sequences of the A, B, C, D ring links.Chapter Ⅱ designed construction lycorine ring systems with the sequences of AD→ADB→ADBC by using Michael reaction as the key reaction, and synthesis study by this method. The features of this method is that the route is simple and concise, and during the early stage of the synthesis it does not involve chirality. The specific experiment used piperic acid as the raw materials, and through such 7-step reactions as bromation, reduction, oxidation, aldehyde group protection, and aldol condensation reaction for the preparation of the key intermediate of lycorine skeleton compound 175, thus successfully constructed the ABD ring links.Chapter Ⅲ is a summary and outlook for the research work. Firstly, it hopes that it is possible to attempt the synthesis of lycorine with compound 175 as the key intermediate. Secondly, it hopes to synthesize the key intermediate compound 190 first, and then, synthesize lycorine with alternative route.Chapter IV reported the specific experimental steps and related compounds synthesis and their nuclear magnetic data.In this thesis, all the molecules structures of relative were confirmed by nuclear magnetic resonance spectrua, and the key intermediate compound 175 was further confirmed by HEMS.