EXPEDITIOUS SYNTHESIS OF AZASUGARS BY THE DOUBLE REDUCTIVE AMINATION OF DICARBONYL SUGARS

Polyhydroxylated pyrrolidines and piperidines were prepared by the dou ble reductive amination of dicarbonyl, sugars with primary amines and NaCNBH3 in MeOH. Stereocontrol in these reactions depended on the natu re of the amine and dicarbonyl sugar. For example, 5-keto-D-fructose ( 7) gave three pyrrolidine stereoisomers, with the N-alkylated 2,5-anhy dro-2,5-imino-D-glucitol predominating. Under similar reaction conditi ons with benzhydrylamine, 5-keto-D-glucose (20) afforded a 96:4 mixtur e of piperidines favoring D-gluco 25A, whereas 5-keto-D-mannose (6) pr oduced a 67:33 mixture enriched in D-manno isomer 40. This method allo wed for the direct and relatively short synthesis of 1-deoxynojirimyci n (DNJ, 1) and 1-deoxymannojirimycin (DMJ, 5) and N-alkylated derivati ves thereof. Similar reactions with O-protected 5-keto-D-glucose deriv atives 21 and 22 were less stereoselective and lower yielding.