A General Synthesis of C6-Azolyl Purine Nucleosides

摘要

Palladium-catalyzed CN bond forming reactions of nucleosides are becoming increasingly important in the synthesis of biologically relevant compounds.[1] Appending heterocyclic systems to nucleosides yields unusual compounds with unique properties and applications. For instance, pyrazole-linked adenosine nucleosides have recently been investigated for their interactions with the adenosine A2 and A3 receptors, which are associated with important biofunctions.[2] These studies showed that compounds containing CN linkages between the heterocycle and the nucleobase display higher activity than those with CC linkages.[2] C6-pyrrolyl compounds have been evaluated as antiarrhythmic agents,[3] and the pyrrolyl moiety has also been investigated as protecting group for the exocyclic amines of purine nucleosides.[4] C6-1,2,4-triazolyl[5] and C6-imidazolyl[6] derivatives are useful for displacement reactions and can be converted into other modified nucleosides. More recently, C6-imidazolyl, C6-benzimidazolyl, and C6-1,2,4-triazolyl nucleoside analogues have found utility in CC bond formation catalyzed by Ni-N-heterocyclic carbene complexes.[7] Despite the assortment of applications for azolyl purines and nucleosides, there is no general method for the synthesis of such compounds. We were attracted to the notion that metal-mediated CN bond formation could provide a single, unifying method for the synthesis of C6-azolyl nucleosides. Herein we report our results for the Pd-catalyzed CN(sp2) bond forming reactions of nucleosides.