Preparation of Zwitterionic Ribonucleoside Phosphoramidites for Solid-Phase siRNA Synthesis

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, lea...

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Bibliographic Details
Published inJournal of organic chemistry Vol. 73; no. 13; pp. 4994 - 5002
Main Authors Smicius, Romualdas, Engels, Joachim W
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 04.07.2008
Amer Chemical Soc
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Summary: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.
Bibliography:Text giving details of the synthesis, purification, and characterization of N4-benzoylcytidine, N6,N6-dibenzoyladenosine, and compounds 1a−e and figures giving 1H NMR, 13C NMR, and HSQC NMR spectra of the new compounds 2−5 and 31P NMR spectra for phosphoramidites 6a−d. This material is available free of charge via the Internet at http://pubs.acs.org.
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ISSN:0022-3263
1520-6904
DOI:10.1021/jo800451m