C-nucleosides. Part 14. Synthesis of (6S)- and (6R)-6-methoxy-6-(β-D-ribofuranosyl) pyran-3(2H,6H)-one. Potential chiral synthons, and 6-(β-D-ribofuranosyl)pyridazine-3-carboxamide, a 2-azanicotinamide C-nucleoside, from 6-hydroxy-6-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)pyran-3(2H,6H)-one

Abstract

The synthesis of (6S)- and (6R)- 6-methoxy-6-(β-D-ribofuranosyl) pyran-3(2H,6H)-one 5a and 5b is described. Acetonization of 6S-compound 5a afforded two products, unexpected spiro compounds 6a and 6b in a 2:1 ratio. The configuration of the spiro-carbon in compounds 6a and 6b was established by NOE experiments. However, acetonization of the 6R-isomer 5b afforded compounds 6a and 6b in a 7:1 ratio. On the basis of the ratio of spiro compounds, the stereochemistry of compounds 5a and 5b was assigned as 6S and 6R, respectively. Treatment of compound 1 with hydrazine in dioxane afforded the 6-hydroxymethylpyridazine 7, a 2-azanicotinamide C-nucleoside, in 58% yield by a novel ring transformation. Krohnke oxidation converted the bromomethylpyridazine 8 into the aldehyde 10. Oxidation of aldehyde 10 in ethanolic potassium hydroxide at –78 °C with ozone afforded the ester 13 in 65% yield. The ester reacted with aq. ammonia in methanol to produce the 2-azanicotinamide C-nucleoside 14, the stereochemistry of which was determined by NOE experiments.