Synthesis and Biological Evaluation of 4′-C,3′-O-Propylene-Linked Bicyclic Nucleosides

Publié le 31 décembre 2010 - European Journal of Organic Chemistry

Auteurs : Marcelo G. Vivas, Daniel L. Silva, Jeremy Malinge, Mohammed Boujtita, Robert Zalesny, Wojciech Bartkowiak, Hans Agren, Sylvio Canuto, Leonardo de Boni, Eléna Ishow, Cleber R. Mendonca, Wilfried Hatton, Julie Hunault, Maxim Egorov, Christophe Len, Muriel Pipelier, Virginie Blot, Virginie Silvestre, Valérie Fargeas, Adjou Ané, Tami Mcbrayer, Mervi Detorio, Jong-Hyun Cho, Nathalie Bourgougnon, Didier Dubreuil, Raymond Schinazi, Jacques Lebreton

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A set of pyrimidine nucleosides fused with a 4'-C,3'-O-propylene bridge was successfully synthesised in 12 steps from 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose, an inexpensive starting material, based on a ring-closing metathesis (RCM) reaction followed by Vorbruggen-type nucleobase coupling. Antiviral and cytotoxicity activities of the targeted modified nucleosides, as well as their phosphoramidate prodrugs, are described.