Preparation of zwitterionic ribonucleoside phosphoramidites for solid-phase siRNA synthesis

J Org Chem. 2008 Jul 4;73(13):4994-5002. doi: 10.1021/jo800451m. Epub 2008 Jun 4.

Abstract

RNA oligomers, carrying 2'-O-modified nucleosides, proved to be extremely useful in different antisense strategies, including RNAi. The 2'-O-alkyl modification, carrying an amino functionality, deserves special attention due to its ability to neutralize the negatively charged phosphate backbone, leading to improved physicochemical and pharmaceutical properties of antisense agents. Here, we report a very short, convenient, and straightforward synthesis of phosphoramidites for all four 2'-aminoethyl-modified natural ribonucleosides, where the aminoethyl group is introduced in a single alkylation step.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Nucleic Acid Conformation
  • Organophosphorus Compounds / chemical synthesis*
  • RNA, Small Interfering / chemical synthesis*
  • Ribonucleosides / chemistry*

Substances

  • Organophosphorus Compounds
  • RNA, Small Interfering
  • Ribonucleosides
  • phosphoramidite