Synthesis, conformational study, glycosidase inhibitory activity and molecular docking studies of dihydroxylated 4- and 5-amino-iminosugars

• Glycosidase inhibitory study of synthesized amino-iminosugars.
• Conformations of amino-iminosugars were assigned by using NMR experiments.
• Glycosidase inhibitory results were supported with the Molecular docking experiments.
• Intramolecular reductive cyclization afforded 4- and 5-amino-iminosugars in good yields.

An efficient methodology for the synthesis of new amino iminosugars 6a, 7a and 8, starting from d-glucose, is reported. The conformational study using 1H NMR data showed that the amino iminosugar 6a exists in the 2C5 while; the 7a and 8 exist in the 5C2 conformation. The inhibition activities with different glycosidases showed that 6a and 7a are poor glycosidase inhibitors. However, amino iminosugar 8 showed selective inhibition against the β-galactosidase (IC50=43 μM, Ki=153 μM). These results are substantiated by the molecular docking studies.

Figure optionsDownload as PowerPoint slide