Synthesis Of Acyclic Nucleosides By Purine N-H Insertion Reaction And Tricyclic Nucleosides By C~6-propargyl Amine Cyclization Reaction

Purine nucleoside analogues have acquired an important role as therapeutic agents in the field of chemotherapy on account of their extensive biological activities. Thereby, modified nucleosides and nucleobases are a pharmacologically diverse family, which includes anticancer compounds, antiviral agents, and immunosuppressive molecules. For several years, there has been an intensive search for drugs effective in chemotherapy of viral diseases like AIDS, herpes simplex, Hepatitis C and cytomegaloviruses. Most of these drugs are analogues of naturally occurring nucleosides. Therefore, the synthesis of diverse purine nucleoside analogues is essential for humans to against disease, and it is also one of our great projects to explore.There are two major parts in this article, mainly including:(1) The syhthesis of acyclic nucleosides by purine N-H insertion reaction. Nucleoside compounds play an important role in the process of the fight against cancer, especially for acyclic nucleoside compounds, they have the unique function of anti-tumor and immune regulation. Therefore, we designed and finished with Sc(OTf)3 as the catalyst to catalyze the purine N-H insertion reactions and synthesis of acyclic nucleosides compounds. We have developed a new method for synthesis of acyclic nucleoside compounds, and opened up a new way to modify the acyclic nucleosides, we also apply this method to pyrimidine compounds, to our surprise, we can also get the corresponding products. In this work, we have got 60 products and the corresponding products were obtained in moderate to good yields(up to 92%).(2) The reaction based on the C6-propargyl amine for the syhthesis of tricyclic nucleosides. Modified nucleobases serve as biomarkers for exposure to chemical carcinogens that form DNA adducts. They also serve as therapeutics, bioprobes for drug design, and sensors to detect light or metal ions. Especially some tricyclic purine nucleoside compounds have excellent fluorescence properties, they have been widely used in biology and biotechnology. For example the application in the field of molecule probe and DNA identification. So the development of new methods to synthesize of diverse tricycle purine nucleoside compounds is particularly important. We take C6-propargyl-9-benzyl adenine as the substrate, Cu Br as catalyst, Cs CO3 as alkali. 29 products were obtained and the yield was up to 89%, it has laid the foundation for the further research.In this paper, we designed and synthesized a series of acyclic nucleoside and tricyclic nucleoside compounds. The reaction operation is simple, mild reaction conditions, short reaction time, high yield and environmental friendly. That will not only enrich the types of nucleosides, but also laid the foundation for the further research.The structure of the compounds that are involved have been determined, including 1H NMR, 13 C NMR, HRMS, 1H-1H NOESY and the single-crystal structure.