The Synthesis Of Tenofovir And Its Analogues By Asymmetric Transfer Hydrogenation

Nucleosides and modified nucleosides paly an important role in people’s every life because of theiroutstanding anti-virus ability, a large number of nucleosides had been applied to clinic. However, somenucleosides have the shortage of high cost, low efficient of the usage and high side effects. In result, thedevelopment of new nucleoside medicines is still an important matter to be solved for chemical andmedical researchers.In many nucleoside and nucleotide compounds, chiral nucleosides and nucleotide make up such alarge proportion, many of them have good biological activity in anti-herpesvirus and anti-retrovirus aspects.Because many chiral acyclic nucleoside compounds are the useful drugs, which had been used into clinic,our reseach group is working on a new synthetic method about chiral nucleoside compounds all the time.Asymmetric transfer hydrogenation had attracted public attention because of its simple operation and highefficiency, which can change carbonyl into hydroxyl. We make asymmetric transfer hydrogenation appliedinto the synthesis of chiral nucleosides, we make the reaction proceed with bivalent Ru and alkaminederivative as catalyst in mild condition, a series of chiral acyclic nucleosides were prepared with the highestyield and ee of the products up to97%. This series of compounds are the precursors and analogues oftenofovir. Thus, we finish the synthesis of tenofovir through asymmetric transfer hydrogenation reaction forthe first time. Our method is simple, which employ achiral materials. And the yield and enantioselective ishigh in the mild reaction condition, so it is a potentially industrial value method as this method is suitablefor a large-scale production.Mannich reaction can provide very useful β-amino carbonyl segment，which is widely used in organicsynthesis. People can synthetize all kinds of potential value Mannich bases through this type of reaction.Given this, we complete the synthesis of purine nucleosides by three-component Mannich reaction, bywhich we can get good yields about purine N9compounds in the mild and simple conditions. Since mostcompounds can proceed in water, the method is green and economic. This reaction has a goodregioselectivity, which has no any N7product. It is a convenient method for the synthesis of purinenucleosides. In the text, we synthetize a series of new purine compounds through asymmetric transferhydrogenation and Mannich reactions, which enrich the numbers of purine compounds and have goodacademic value and potential application significance.