Publication Date:
2012-03-14
Description:
2'- O -Aminooxymethyl ribonucleosides are prepared from their 3',5'-disilylated 2'- O -phthalimidooxymethyl derivatives by treatment with NH 4 F in MeOH. The reaction of these novel ribonucleosides with 1-pyrenecarboxaldehyde results in the efficient formation of stable and yet reversible ribonucleoside 2'-conjugates in yields of 69–82%. Indeed, exposure of these conjugates to 0.5 M tetra- n -butylammonium fluoride (TBAF) in THF results in the cleavage of their iminoether functions to give the native ribonucleosides along with the innocuous nitrile side product. Conversely, the reaction of 5-cholesten-3-one or dansyl chloride with 2'- O -aminooxymethyl uridine provides permanent uridine 2'-conjugates, which are left essentially intact upon treatment with TBAF. Alternatively, 5'- O -aminooxymethyl thymidine is prepared by hydrazinolysis of its 3'- O -levulinyl-5'- O -phthalimidooxymethyl precursor. Pyrenylation of 5'- O -aminooxymethyl thymidine and the sensitivity of the 5'-conjugate to TBAF further exemplify the usefulness of this nucleoside for modifying DNA sequences either permanently or reversibly. Although the versatility and uniqueness of 2'- O -aminooxymethyl ribonucleosides in the preparation of modified RNA sequences is demonstrated by the single or double incorporation of a reversible pyrenylated uridine 2'-conjugate into an RNA sequence, the conjugation of 2'- O -aminooxymethyl ribonucleosides with aldehydes, including those generated from their acetals, provides reversible 2'- O -protected ribonucleosides for potential applications in the solid-phase synthesis of native RNA sequences. The synthesis of a chimeric polyuridylic acid is presented as an exemplary model.
Print ISSN:
0305-1048
Electronic ISSN:
1362-4962
Topics:
Biology
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