Highly Enantioselecvtive Organocatalytic Total Synthesis Of (+)-Gelsemine

Total synthesis of natural products has always been a challenging and attractive area in synthetic organic chemistry. Being both a fine art and a precise science, total synthesis of natural products serves to inspire organic chemists to develop new methods towards efficient synthesis of complex natural products. Due to increasingly severe environmental problems and improvements achieved in other disciplines, exploring efficient biosynthetic methods of complex natural products has become a hot topic in chemical research, which is crucial to promote the field of synthetic methodology, solve the problems associated with the supply and structure identification of natural products, facilitate the discovery of new skeleton of chemical compounds, and then provide a variety of bioactive compounds for biological study.No matter how excellent, the synthetic design would be nothing without trial in laboratory. In Chapter 1, recent studies on the synthesis of gelsemine is reviewed, including the disconnection and connection approach to construct the skeleton of gelsemine.In Chapter 2 our investigations on the total synthesis of (±)-and (+)-gelsemine is described. Stereogenic centers at C15 and C16 were established by a Diels-Alder reaction. The pyrrolidine and C20 quaternary carbon center were contructed by an intramolecular aldol reaction. Finally, oxindole fragment was introduced to complete the assembly of gelsemine. The total synthesis of racemic gelsemine was finished in only 13 steps. Subsequently, organocatalyzed asymmetric Diels-Alder reaction was used to build lactone 2-66b with high enantioselectivity. Thus the total synthesis (+)-gelsemine was realized. Furthermore, intermediate (+)-2-73 was obtained on a 1.1-g scale within one set of operations.