Chemical Approaches to Carbocyclic Nucleosides

Abstract

Nucleoside analogues are at the forefront of antiviral therapy for last decades. To circumvent some of their limitations, based on their metabolism, and in order to improve their anti-viral potency and selectivity, several families of nucleoside analogues have been described through structural modifications at the sugar and heterocycles. The replacement of the oxygen of the nucleoside by a methylene has led to the family of carbocyclic (or cyclopentane) nucleoside analogues. Various potent anti-HIV and anti-HBV drugs belong to this family. Main syntheses of carbocyclic analogues of nucleosides used Diels-Alder reactions (in racemic or asymmetric series), but also started from carbohydrates (ribose, glucose), as a source of optically active compounds, which then had to be transformed into carbacycles under various conditions. The growing interest in carbocyclic nucleosides has led several groups, including ours, to develop new analogues and to explore novel routes. This article will review some of the recent chemistry developed on selected five-membered ring carbocyclic nucleosides.

Keywords: antiviral compounds; carbocyclic nucleosides; transition-metal-catalyzed reactions.