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

W. Hatton , Julie Hunault (1) , M. Egorov , C. Len (2) , M. Pipelier , V. Blot , V. Silvestre , Valérie Fargeas (3) , A. Ane (1) , T. Mc Brayer , M. Detorio , J.H. Cho , Nathalie Bourgougnon (4) , Didier Dubreuil (3) , R.F. Schinazi , Jacques Lebreton (3)

1 CEISAM - Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation
2 U3B - Unité de Biotechnologie, Biocatalyse et Biorégulation
3 LSOHOOM - Laboratoire de Synthèse Organique (Hétérochimie organique, organoéléments et matériaux)
4 LBCM - Laboratoire de Biotechnologie et Chimie Marines

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.

Domaines: Bactériologie

W. Hatton, Julie Hunault, M. Egorov, C. Len, M. Pipelier, et al.. Synthesis and Biological Evaluation of 4′-C,3′-O-Propylene-Linked Bicyclic Nucleosides. European Journal of Organic Chemistry, 2011, 36, pp.7390-7399. ⟨10.1002/ejoc.201100859⟩. ⟨hal-00858162⟩