Conversion of 2-deoxy-d-ribose into 2-amino-5-(2-deoxy-β-d-ribofuranosyl)pyridine, 2′-deoxypseudouridine, and other C-(2′-deoxyribonucleosides)

Organic & Biomolecular Chemistry Pub Date: 2003-08-18 DOI: 10.1039/B306341K

Abstract

The synthesis of 2-amino-5-(2-deoxy-β-D-ribofuranosyl)pyridine 2a, 2-amino-5-(2-deoxy-α-D-ribofuranosyl)pyridine 23, 2-amino-5-(2-deoxy-β-D-ribofuranosyl)-3-methylpyridine 2b, 2-amino-5-(2-deoxy-α-D-ribofuranosyl)-3-methylpyridine 29 and 5-(2-deoxy-β-D-ribofuranosyl)-2,4-dioxopyrimidine [2′-deoxypseudouridine] 30a is described. These C-nucleosides are prepared either from 2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-D-ribofuranose 15 or from 2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-D-ribono-1,4-lactone 16, which are themselves prepared from 2-deoxy-D-ribose 13. The sugar derivatives are first allowed to react with the appropriate 5-lithio-pyridine or 5-lithio-pyrimidine derivatives, which are prepared from 5-bromo-2-(dibenzylamino)pyridine 12a, 5-bromo-2-[bis(4-methoxybenzyl)amino]pyridine 12b, 5-bromo-2-dibenzylamino-3-methylpyridine 25 and 5-bromo-2,4-bis(4-methoxybenzyloxy)pyrimidine 33. The products from the reactions between the lithio-derivatives and the lactol 15 are cyclized under Mitsunobu conditions; the products from the reactions between the lithio-derivatives and the lactone 16 are first reduced with L-Selectride before cyclization, also under Mitsunobu conditions. In all cases, the β-anomers of the protected C-nucleosides are the predominant products. Finally, the separation of the α- and β-anomers and the removal of all of the protecting groups are described.

Graphical abstract: Conversion of 2-deoxy-d-ribose into 2-amino-5-(2-deoxy-β-d-ribofuranosyl)pyridine, 2′-deoxypseudouridine, and other C-(2′-deoxyribonucleosides)
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