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Synthesis of 5'-methylene-phosphonate furanonucleoside prodrugs: application to D-2'-deoxy-2'-?-fluoro-2'-?-C-methyl nucleosides.

ABSTRACT: A new and facile synthetic pathway to metabolically stable 5'-methylene-bis(pivaloyloxymethyl)(POM)phosphonate furanonucleoside prodrugs is reported. The key step involves a Horner-Wadsworth-Emmons reaction of a tetra(pivaloyloxymethyl) bisphosphonate salt with appropriately protected 5'-aldehydic nucleosides. This efficient approach was applied for the synthesis HCV related 2'-deoxy-2'-?-fluoro-2'-?-C-methyl nucleosides.

SUBMITTER: Pradere U

PROVIDER: S-EPMC3470451 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Synthesis of 5'-methylene-phosphonate furanonucleoside prodrugs: application to D-2'-deoxy-2'-α-fluoro-2'-β-C-methyl nucleosides.

Pradere Ugo U Amblard Franck F Coats Steven J SJ Schinazi Raymond F RF

Organic letters 20120823 17

A new and facile synthetic pathway to metabolically stable 5'-methylene-bis(pivaloyloxymethyl)(POM)phosphonate furanonucleoside prodrugs is reported. The key step involves a Horner-Wadsworth-Emmons reaction of a tetra(pivaloyloxymethyl) bisphosphonate salt with appropriately protected 5'-aldehydic nucleosides. This efficient approach was applied for the synthesis HCV related 2'-deoxy-2'-α-fluoro-2'-β-C-methyl nucleosides. ...[more]

PMID: 22917194

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