Design and synthesis of α-carboxy phosphononucleosides.
Rhodium catalyzed O-H insertion reactions employing α-diazophosphonate 20 with appropriately protected thymidine, uridine, cytosine, adenosine and guanosine derivatives leads to novel 5'-phosphononucleoside derivatives. Deprotection led to a novel series of phosphono derivatives bearing a carboxylic acid moiety adjacent to the phosphonate group with potential antiviral and/or anticancer activity. The phosphononucleosides bearing an α-carboxylic acid group are envisaged as potential diphosphate mimics. Conversion to mono- and diphosphorylated phosphononucleosides has been effected for evaluation as nucleoside triphosphate mimics. Most of the novel phosphononucleosides proved to be inactive against a variety of DNA and RNA viruses. Only the phosphono AZT derivatives 56-59 showed weak activity against HIV-1 and HIV-2.
Department of Chemistry, Analytical and Biological Chemistry Research Facility, University College Cork, Ireland.
Sebastien
S
Debarge
Jan
J
Balzarini
Anita R
AR
Maguire
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D015497:HIV-1 / Q000737:chemistry* / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D063065:Organophosphonates / Q000737:chemistry; D010766:Phosphorylation; D012238:Rhodium / Q000737:chemistry; D015215:Zidovudine / Q000138:chemical synthesis* / Q000737:chemistry
D000998:Antiviral Agents; D009711:Nucleotides; D063065:Organophosphonates; D015215:Zidovudine; D012238:Rhodium