Cycloadditions of Sugar-Derived Nitrones Targeting Polyhydroxylated Indolizidines

The 1,3 dipolar cycloaddition reactions of three pentose- derived pyrroline N-oxides with mono- and disubstituted alkenes are reported. A strong dependence of the diastereoselectivity of the cycloadditions on the relative configuration of the nitrone stereocentres was observed. Further transformation of the reaction products allowed the synthesis of four new tetrahydroxylated indolizidines. Their activity as glycosidase inhibitors was evaluated against a panel of commercially available glycosidases. The specificity of inhibitory activity against amyloglucosidase and α-mannosidases depends on the configuration at C-2 of the indolizidine moiety.