Synthesis of Purine Derivatives as Scaffolds for a Diversity of Biological Activities

A.      Conejo-Garcia; O.      Cruz-Lopez; V.      Gomez-Perez; F.      Morales; M.      E. Garcia-Rubino; M.      Kimatrai; M.      C.Nunez; J.      M. Campos

doi:10.2174/138527210793358240

Abstract

The purine ring is undoubtedly among the most ubiquitous of all the heterocyclic compounds. This arises not only from the universal occurrence of adenine and guanine in DNA and RNA and of additional modified derivatives in the various tRNAs but also from the subsidiary uses of the ring system in a great number of biochemical systems. The development of new methods for metal-mediated coupling with aryl or heteroaryl halide substrates has expanded the range of synthetically accessible arylpurine derivatives. Aryl boronic acids have proved to be extremely available reagents for metal-mediated C-C and C-N coupling reactions. Coupling reactions resulting in C-C bond formation are catalyzed by palladium and nickel catalysts at positions C2, C6 and C8. The reactivity at C6 position has been demonstrated using fluoro-, chloro-, bromo-, iodo-, sulfanyl, sulfonyl, sulfonyloxy- and azole-substrates. The ease of obtaining the activated purine substrates is an important factor when selecting appropriate coupling conditions. Copper-mediated N-arylations occur at positions N7 and N9. These methods are also applicable using solid-supported purine substrates and provide convenient access to structurally unique derivatives with applications in drug discovery. Continuing advances in this field can be expected to result through improved mechanistic understanding and the development of new catalysts and ligands.

Keywords: Alkyl-purine derivatives, aryl-purine derivatives, cross-coupling, ferrocene-modified purines, fluorinated compounds, microwave, nucleosides, solid-phase synthesis, antiparasitic agents, cyclin-dependent kinase inhibitors, 5-alkylamino-4-amino-6-arylthiopyrimidine, cyclohexyl nucleosides, 9-Phenyl-9H-purin-6-amines, 5-amino-1-phenyl-1H-imidazole-4-carbonitriles, methyl ethyl ketone, perfluoroalkylation reaction, Tetrabutylammonium triphenyldifluorosilicate, imidazolium-carbene ligand, Phosphonated azaheterocycles, C6-phosphonated purine nucleosides, 2-Amino-6-(1,2,4-triazol-4-yl)purine, Disubstituted Purines, tetrabutylammonium nitrate, trifluoroacetic anhydride, 2,6-Dichloropurine, tributyltin chloride, trimethylsilyl chloride, hexamethyldisilazane, anhydrous acetonitrile, 1,2-dichloroethane, dihydrodiazepinopurine, Mycobacterium avium, N,N-dimethylacetamide, TETRASUBSTITUTED PURINES, diaminopyrimidine