Synthesis of N-substituted 2-carboxamido azasugars via sequential Ugi-3CR/cyclization reaction

A convenient synthesis of novel N-substituted 2-carboxamido azasugars has been developed from a sugar-derived precursor. The one-pot sequential process involves the reaction of 5-O-tosylate ribose with amines and isocyanates, promoted by a catalytic amount of phosphoric acid, to afford the corresponding piperidine-based azasugar derivatives in good yields. This strategy provides efficient access to a series of functionalized azasugar C-glycosides featuring a carboxamido substituent at the pseudoanomeric position with high stereoselectivity. The utility of this methodology was further demonstrated by the synthesis of a polyhydroxylated N-substituted 2-carboxamido azasugar from d-mannose.