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

• Published in: European Journal of Organic Chemistry 2011-12, Vol.2011 (36), p.7390-7399
• Main Authors: Hatton, Wilfried, Hunault, Julie, Egorov, Maxim, Len, Christophe, Pipelier, Muriel, Blot, Virginie, Silvestre, Virginie, Fargeas, Valérie, Ané, Adjou, McBrayer, Tami, Detorio, Mervi, Cho, Jong-Hyun, Bourgougnon, Nathalie, Dubreuil, Didier, Schinazi, Raymond F., Lebreton, Jacques
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Bacteriology; Biological and medical sciences; Carbohydrates. Nucleosides and nucleotides; Chemistry; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Glycosylation; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Life Sciences; Medical sciences; Medicinal chemistry; Metathesis; Microbiology and Parasitology; Nitrogen heterocycles; Nucleic acids; Nucleic bases, nucleotides; Nucleosides; Nucleosides, nucleotides and oligonucleotides; Organic chemistry; Pharmacology. Drug treatments; Preparations and properties
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201100859

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‐α‐D‐glucofuranose, an inexpensive starting material, based on a ring‐closing metathesis (RCM) reaction followed by Vorbrüggen‐type nucleobase coupling. Antiviral and cytotoxicity activities of the targeted modified nucleosides, as well as their phosphoramidate prodrugs, are described. An efficient route to a set of pyrimidine nucleosides fused with a 4′‐C,3′‐O‐propylene bridge has been developed. Antiviral and cytotoxicity activities of these bicyclic nucleosides, as well as their phosphoramidate prodrugs, are presented.