An Overview of Diazine Nucleoside Analogues

Early work on antiviral agents focused on traditional nucleoside analogues in which the base was linked to one or other of the naturally occurring sugars. Some of these were indeed shown to possess anti-metabolic properties, but it became apparent that their usefulness was severely limited by instability and poor selectivity. Since the discovery of the first successful anti-viral drug, acyclovir, in 1974 by Gertrude "Trudy" Elion, interest has diversified towards compounds in which the heterocycle and sugar components of the nucleoside differ significantly from the natural form. These novel types of nucleosides act as anticancer, antiviral or antibacterial drugs. The intense search for clinically useful nucleoside derivatives has resulted in a wealth of new approaches for their synthesis. In this review, we will give an overview of the synthesis of some pyrimidine nucleosides according to their structural types (e.g., acyclics, carbocyclics, and C5- substituted pyrimidine nucleosides), including compounds having "unnatural" L-stereochemistry, along with the synthetic routes of some selected examples. The article also refers to other relevant review articles that have covered particular areas of investigation or have dealt in depth with a single compound.