| Alkaloids are a kind of natural products with significant physiological activities,which are widely found in various plants.Among natural alkaloids,indole alkaloids and its derivatives represent about a quarter of all alkaloids.Gelsmium elegans,commonly known as Duanchangcao in China,is a highly toxic plant.Gelsemine,isolated from gelsmium elegans,is an oxyindole alkaloid.Studies on the activities of gelsmium alkaloids have revealed that gelsmium alkaloids have many biological functions,such as anti-tumor,analgesia,immune regulation,pupil dilation and promoting hematopoietic function.The structure of gelsemine was determined by X-ray single crystal diffraction in 1959.Its cage-like skeleton and its interesting biological activities has attracted the interests of many research groups in the world.So far,eight research groups have reported the total synthesis of gelsemine,only three of them are asymmetric total synthesis.It is still necessary to develop new synthetic strategies to synthesize gelsemine because of the potential pharmacological activities of this gelsmium alkaloids.In this thesis,Michael addition reaction is used as the key transformation for carbon-carbon bond construction.We aim to develop a general route to achieve asymmetric total synthesis of gelsemine.This thesis is divided into four chapters.The first chapter summarizes the separation,classification and activities of gelsmium alkaloids in recent years,the research progress of total synthesis of gelsmium alkaloids is also provided.Chapter 2 describes the establishment of synthetic methodology towards the construction of seven-membered rings in gelsemium alkaloids and its application in synthesis.We have developed a method to prepare oxygen bridged intermediates.Application of this new method in the total synthesis of gelsemine is studied.In the third chapter,the asymmetric total synthesis of gelsemine was studied.The cage ring was constructed from 1,4-butene diol via intramolecular double Michael addition reactions.This chapter also describes the problems encountered as well as the strategies to solve them on the way of total synthesis.Chapter 4 records the experimental operation and spectral data of intermediates involved in the synthesis process. |
