Synthesis of chimeric oligonucleotides containing phosphodiester, phosphorothioate, and phosphoramidate linkages

Org Lett. 2000 Jun 29;2(13):1819-22. doi: 10.1021/ol005842h.

Abstract

[reaction: see text] H-Phosphonate monomers of 2'-O-(2-methoxyethyl) ribonucleosides have been synthesized. Oxidation of oligonucleotide H-phosphonates has been optimized to allow the synthesis of oligonucleotides containing either 2'-deoxy or 2'-O-(2-methoxyethyl) ribonucleoside residues combined with three different phosphate modifications in the backbone, i.e., phosphodiester (PO), phosphorothioate (PS), and phosphoramidate (PN). Phosphodiester linkages were introduced by oxidation with a cocktail of 0.1 M Et(3)N in CCl(4)/Pyr/H(2)O (5:9:1) without affecting phosphorothioate or phosphoramidate linkages. For the synthesis of phosphoramidate-modified oligonucleotides, N(4)-acetyl deoxycytidine-3'-H-phosphonate monomers were used to avoid transamination during the oxidation step.

MeSH terms

  • Oligonucleotides / chemical synthesis*
  • Oligonucleotides / chemistry
  • Oligonucleotides, Antisense / chemical synthesis*
  • Oligonucleotides, Antisense / chemistry
  • Organothiophosphorus Compounds / chemical synthesis
  • Organothiophosphorus Compounds / chemistry
  • Thionucleotides / chemistry

Substances

  • Oligonucleotides
  • Oligonucleotides, Antisense
  • Organothiophosphorus Compounds
  • Thionucleotides