Synthesis of branched-chain nitro and amino sugars by the nitromethane route

Abstract

Addition of 5- O-benzyl-1,2- O-isopropylidene-α- d- erythro-pentofuranos-3-ulose ( 1) to excess nitromethane and 1 molar equivalent of sodium methoxide in methanol gave 5- O-benzyl-1,2- O-isopropylidene-3- C-nitromethyl-α- d-ribofuranose ( 2) in 60% yield. Under essentially the same conditions, 1,2:5,6-di- O-isopropylidene-α- d- ribo-hexofuranos-3-ulose ( 4) yielded 1,2:5,6-di- O-isopropylidene-3- C-nitromethyl-α- d-glucofuranose ( 5) in 71% yield. Treatment of the ketose 4 with nitromethane and sodium hydride gave 5 and the allo-epimer 5a in a total yield of 91%. The proof of structure of the branched-chain nitro sugars is described. Selective hydrolysis of 5 gave the partially blocked into sugar 6, which was converted by catalytic hydrogenation into the branched-chain amino sugar 9 (characterized as its N-acetyl derivative). Oxidation of 6 with sodium metaperiodate, followed by reduction of the aldehydo-derivative with sodium borohydride, afforded 1,2- O-isopropylidene-3- C-nitromethyl-α- d-xylofuranose ( 7). Reduction of 7 yielded the partially blocked amino sugar 13. Compounds 7 and 13 were unblocked to afford the unsubstituted, branched-chain, nitro and amino sugars. The 3-acetate of 5 was converted by a Schmidt-Rutz reaction into a nitroolefin (not isolated), which was hydrogenated with sodium borohydride in ethanol to yield mainly 3-deoxy-1,2:5,6-di- O-isopropylidene-3- C-nitromethyl-α- d-glucofuranose ( 17, assigned on basis of its n.m.r. spectrum).