Synthesis Of 9-substituted Purine Nucleosides

Various modified nucleosides play important roles in the anti-virus and anti-tumor process. Currently, the nucleoside compounds accounted for a large proportion in the antiviral drugs, which had marketed and been used in clinical studies. Nevertheless, there are some insufficiencies, which still can not be avoided, such as: the high cost of synthesis, weak performance, short duration, toxic side effects and so on. Therefore, the development of efficient low-cost and low toxicity nucleoside drugs are still the majority challenges for the chemical and pharmaceutical scientists.In this paper, we studied the synthesis of N-9-substituted purine nucleoside analogues, including the synthesis of N-9-alkylether-substituted purine nucleoside analogues and N-9-aryl-substituted purine compounds. We first attempt to use intermolecular hydrogen abstraction reaction to synthesize a novel class of 9-alkylether-substituted purine nucleoside analogues from various purines and ethers. And we first synthesize N-9 arylpurine in presence of 10% CuBr as catalyst and diaryliodonium salts as arylation reagent.We also studied the one-pot synthesis of C-6 thiopurine nucleosides derivatives. We used thiourea as the sulfuration reagent of purine C-6 position, easily synthesized 6-thiopurine nucleoside analogues in ethanol under microwave irradiation. The reaction is not only high yield, short reaction time, and low energy consumption and environmental friendly. And this is a new approach to synthesize 6-thiopurine nucleoside analogues.Pyrimidine compounds have good biological activity. But because of the highly polar, it hindered their bioavailability. So, for increasing the solubility of these compounds, we decided to selective alkylation at pyrimidines N-3 position. And this method was easy and efficient.We report that this opens an effective new avenue for modification at purine nucleosides, and these results have good value in academy and application.