Efficient Synthesis of 5-(β-D-Ribofuranosyl)nicotinamide and Its α-Isomer

Krzysztof W. Pankiewicz, Elzbieta Sochacka, Marek M. Kabat, Lech A. Ciszewski, Kyoichi A. Watanabe

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23 Scopus citations

Abstract

Condensation of 2,3-O-isopropylidene-5-O-(tetrahydropyranyl)-D-ribonolactone (3) with 3-cyano-5-lithiopyridine afforded 1-(3-cyanopyridin-5-yl)-2,3-O-isopropylidene-5-O-(tetrahydropyranyl)-β-D-ribofuran-1-ulose (5a), which was reduced with NaBH4 to a 1:1 allo/altro mixture of 5-[2,3-O-isopropylidene-5-O-(tetrahydropyranyl)-Dpentitol-1-yl]-3-cyanopyridine (7a). The isomers were chromatographically separated. Treatment of allo-7a with TsOH/MeOH gave 5-(2,3-O-isopropylidene-D-allo-pentitol-1-yl)-3-cyanopyridine (allo-8a), which was acetonated to give 5-(2,3:4,5-di-O-isopropylidene-D-o(Zo-pentitol-1-yl)-3-cyanopyridine (allo-9a). Mesylation of allo-9a to allo-10 followed by acid hydrolysis with CF3CO2H/CHCl3 afforded 5-(α-D-ribofuranosyl)-3-cyanopyridine (11a). The β-isomer la was synthesized in a similar manner from altro-7a. Inversion of the configuration at the C-1 position of 6-(2,3:4,5-di-O-isopropylidene-D-allo-pentitol-1-yl)-2-bromopyridine (allo-9b) into the corresponding altro isomer altro-9b was achieved albeit in modest yield (24%) by mesylation of allo-9b to allo-10b followed by treatment with potassium superoxide. Interconversion of altro-9a or -9b into the corresponding allo derivatives was readily achieved in excellent yield by oxidation with CrO3/pyridine/Ac2O to the corresponding keto intermediates 19 followed by borohydride reduction. Treatment of the 1-O-mesylate allo-10b with NaN3 in DMF afforded the corresponding 1-azido-1-deoxy altro derivative (17). Similar treatment of the 1-O-triflyl derivatives allo-15a,b with NaN3 or NaOAc in DMF surprisingly afforded allo-9a,b in good yield.

Original languageEnglish (US)
Pages (from-to)3473-3479
Number of pages7
JournalJournal of Organic Chemistry
Volume53
Issue number15
DOIs
StatePublished - Feb 1 1988

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