C-nucleosides : synthesis and biological activity

Studies on synthesis and biological activity of modified nucleoside and nucleotide analogues have been an active field of research in medicinal chemistry for years [1, 2]. High biological activity of naturally occurring C-nucleosides, for example showdomycin 5, formycins A 41 and B 42 motivated many research groups to study their analogues and structurally similar compounds. Furthermore, since C-nucleosides lack N-glycosidic bond they are more resistant to enzymatic hydrolysis [3]. This review collects selected methods of synthesis of C-nucleoside analogues which were analyzed to point out the most interesting and inspiring synthetic strategies, in many cases based on contemporary achievements. These strategies first of all take advantage of the formation of the C–C bond between the anomeric carbon atom of the sugar or pseudosugar moieties and the carbon atom of the modified nucleobases. Less common approach relies on the de novo construction of heterocyclic rings employed as nucleobase substitutes. Though years many new compounds sometimes of significant structural complexity have been obtained and characterized to find several examples endowed with high antiviral and cytostatic activity. The biological activity of the C-nucleoside analogues screened so far encourages us to continue a search for new potential drugs within compounds equipped with this attractive structural motif