The Design And Synthesis Of Purine Nucleoside Analogues Containing Fluorine At The Side Chain Of N-9

In recent years, the derivatives of acyclic nucleoside drugs are very hot, for the acyclic nucleoside drugs occupies very large proportion in clinical application. These drugs can be very effective into DNA chin, to destyuct viral replication system and stop the elongation of DNA chain. Because of these drugs important effects, so the study of such drugs has also made a lot of achievements. As for the cyclic nucleotide(acid) compounds aftereffect relations in-depth study, it was found that the introduction of fluorine atoms can effectively change their biological activity, Mainiy because of strong electronegativity and the atomic radius is small of fluorine atoms, fluorine atoms can with carbon atoms to form stable C-F keys. So the acyclic nucleoside drugs occupie very important position.FBSM is by Shanghai YouJiSuo Hu Jinbo professor as well as the Japanese ancient house university Shibata team independently developed, has been in the Mannich reaction, Michael addition reaction and the asymmetric allylic single fluorine in the methylation reaction to obtain the very good application, But there is no report of addition reaction about FBSM with allene compounds, This paper first reports the addition reaction of FBSM and the alkene compounds. This synthetic method affords acyclic nucleosides in good yields(11 examples, 87-96% yields). The main Products have been characterized by single crystal X-ray diffraction.In addition, we try the Michael addition reaction of FBSM and 9-ester-9H-purines, we successfully obtained another fluorine substituted acyclic nucleosides.This paper opens up a new synthetic route acyclic nucleoside, synthesis of acyclic nucleosides with diverse side chains. Their structures were conformed by 1H NMR, 13 C NMR, 19 F NMR and HRMS...