Synthesis of nucleoside aminooxy acids

First nucleoside aminooxy acids were synthesized from furanoid sugar phthalimidooxy acids by N-glycosylation with uracil, thymine, N-benzoylcytosine, 6-N-benzoyladenine and 2-N-acetyl-6-O-diphenylcarbamoylguanine. Boc or Fmoc protected uridine aminooxy acid derivatives have also been prepared. As oxyamine protecting group, the phthalimido group was shown to be instable in MeOH, leading to the imide ring-opening product in a reversible way. This reaction was accelerated under acid or basic conditions. A uridine dimer linked by N-oxy amide has also been prepared by coupling of uridine aminooxy ester with uridine phthalimidooxy acid. These nucleoside aminooxy acids might constitute useful building blocks for the development of novel RNA mimics and conjugates with other biomolecules or reporter compounds.

Graphical abstractDownload full-size image