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A series of deoxynojirimycin-triazole hybrid iminosugars had been prepared and investigated against a panel of glucosidases. Compound 10f (IC50 = 0.063 ± 0.006 mM) exhibited improved inhibitory potency against α-glucosidase compared to 1-deoxynojirimycin (IC50 = 0.155 ± 0.015 mM). Moreover, analysis of the kinetics of enzyme inhibition by using Lineweaver–Burk plots indicated that 10f inhibited α-glucosidase in a competitive manner. Compound 10m displayed moderate inhibition of α-glucosidase and β-glucosidase. The structure-activity relationships indicated that the introduction of the phenyl group and the nature of 4-position substituents on the phenyl ring had significant effects on the glucosidase inhibitory potency of the compounds. [ABSTRACT FROM AUTHOR]

A straightforward synthesis of N-alkylated 1-deoxynojirimycin derivatives modified at the 6-O-position has been described. The key intermediate in the synthesis of target compounds was 2,3,4-tri-O-benzyl-1,5-dideoxy-1,5-imino-D-glucitol, which was prepared from 2,3,4,6-tetra-O-benzyl-1,5-dideoxy-1,5-imino-D-glucitol. Optimal conditions have been established for the synthesis of the key intermediate by varying reaction parameters. Reductive amination and subsequent alkylation of the 6-O-position followed by hydrogenolysis were the main reaction steps, which gave target compounds 6-O-ethyl-N-octyl-1,5-dideoxy-1,5-imino-D-glucitol and 6-O-butyl-N-octyl-1,5-dideoxy-1,5-imino-D-glucitol. This synthetic route is flexible and can be useful for the synthesis of other lipophilic iminosugar derivatives. [ABSTRACT FROM AUTHOR]