Synthesis Of Indolizidine And Pyrrolidine Derivatives

This thesis includes four parts.In the first part, the basis and significance of our research topic is given. Then the multi-component reactions, indolizidines, pyrrolidines and the synthesis of them are described in detail. The creative points of the research subject are also proposed.In the second part, the synthesis of indolizidine-5(1H)-ones, which may have potential antitumor, antibacterial and other biological activities, has been developed by a new ABC2-type reaction using 2,2-dimethyl-1,3-dioxane-4,6-dione or diethyl malonate,(pyridin-2-yl)methanamine or(pyrizin-2-yl)methanamine and 3-aryl-1-azaaryl-prop-2-en-1-ones as raw materials. The synthetic method has many advantages such as operational simplicity, mild reaction conditions and high efficiency of bond formation.In the third part, pyrrolidine derivatives with significant biological activities are selected as targeted compounds. A new multi-component reaction has been developed to synthsize a series of highly substituted pyrrolidine derivatives. At the same time three sigma-bond and four chiral center may proceed in this reaction. In addition, pyridine or pyrazine group is introduced to achieved the synchronization function of its skeleton. Our resarch not only benefits to provide efficient method to highly substituted pyrrolidine derivatives in organic synthesis, but also to enrich the pyrrolidine compound library.In the last part, spiro[indoline-3,2’-pyrrolidin]-2-one skeletons widely found in nature have therapeutic potential. A novel type of multicomponent reaction involving 3-aryl-1-azaaryl-prop-2-en-1-ones, isatins and(pyridine-2-yl)methanamine or(pyrizin-2-yl)methanamine was studied to synthesis a series of spiro[indoline-3,2’-pyrrolidin]-2-one derivatives. Pyridine or pyrazine group is introduced to improve biological activity of its derivatives. In addition, the method have many advantages including mild conditions and simple product separation.In summary, indolizidine,pyrrolidine and spiro[indoline-3,2’-pyrrolidin]-2-one derivatives in our research were reported for the first time and characterized by IR, 1H NMR, 13 C NMR and HRMS. Among these compounds, some of the targeted compounds were confirmed by X-ray diffraction analysis respectively. All of the possible reaction mechanisms were put forward. The synthetic strategy for the preparation and modification of indolizidine-5(1H)-one, pyrrolidine and spiro[indoline-3,2’-pyrrolidin]-2-one skeletons as substructures in natural products was developed and there are many advantages including simple and high efficiency of one-pot reaction with these protocols. At the same time pyridine or pyrazine group is introduced in order to improve biological activity of its derivatives, which has the synchronization function of the skeleton. In a word, our research not only benefits to expand the application scope of multicomponent cascade reactions in organic synthesis, but also to enrich the compound library for new drug discovery.