Synthesis of nucleoside 3'-alkylphosphonates: Intermediates for assembly of carbon-bridged dinucleotide analogues

Article abstract of DOI:10.1021/jo00079a027

Several 3'-modified nucleosides have been prepared, through an initial Wittig or Horner-Wadsworth-Emmons condensation with an adenosine 3'-ketone, followed by catalytic hydrogenation of the resulting olefin. Subsequent reaction of the 3'α-methylene carboxylate with the lithium salt of diethyl ethylphosphonate gave a β-keto phosphonate, while reaction of the methylene carboxylate with LDA, diethyl chlorophosphite, and O₂ gives the corresponding α-phosphono ester. These new nucleoside phosphonates can be viewed as analogues of natural phosphates and also can serve as synthetic intermediates for preparation of carbon-bridged dinucleotide analogues. To give the first such example, the β-keto phosphonate 13 was allowed to react with a nucleoside 5'-aldehyde, affording the dinucleoside enone 23.