Synthesis of 5'-methylene-phosphonate furanonucleoside prodrugs: application to D-2'-deoxy-2'-α-fluoro-2'-β-C-methyl nucleosides.
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.
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Decatur, Georgia 30033, USA.
Ugo
U
Pradere
Franck
F
Amblard
Steven J
SJ
Coats
Raymond F
RF
Schinazi
D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis; D016174:Hepacivirus / Q000187:drug effects*; D008697:Methane / Q000031:analogs & derivatives; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010756:Phosphoric Acids / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000577:Amides; D000998:Antiviral Agents; D009705:Nucleosides; D010756:Phosphoric Acids; D011355:Prodrugs; C030011:carbene; C011067:phosphoramidic acid; D008697:Methane