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

摘要

The synthesis of 2-amino-5-(2-deoxy-β-D-ribofuranosyl) pyridine 2a, 2-amino-5-(2-deoxy-α-ribofuranosyl)-pyridine 23, 2-amino-5-(2-deoxy-β-D-ribofuranosyl)-3-methylpyridine 2b, 2-amino-5-(2-deoxy-α-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-2, 3-diyl)-D-ribofuranose 15 or form 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-methylpyrine 25 and 5-bromo-2, 4-bis(4-methoxybenzyl)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-Selecride 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.