Fluorinated piperidine iminosugars and their N-alkylated derivatives: Synthesis, conformational analysis, immunosuppressive and glycosidase inhibitory activity studies

摘要

AbstractThe fluorinated piperidine iminosugars2a-4aand theirN-octyl andN-decyl derivatives2b,c-4b,cwere synthesized fromd-mannose/d-xylose using nucleophilic fluorination as the key step. The conformation of iminosugars2/3, either2C5or5C2, was assigned based on the1H NMR studies at different pH. Immunomodulatory activity of2a,c-4a,cwas examined using Mixed Lymphocyte Reaction (MLR) and B-cell assay. TheN-alkylated fluorinatedd-manno-iminosugars3b/4bwere found to be better immunosuppressive agents (IC50?=?5–6?μM) on T-cells. The fluorinated iminosugar3a/4aact as potent and selective inhibitors ofβ-glucosidase (IC50?=?4–8?μM). TheN-alkyl-iminosugars4b-cwere found to be moderate inhibitors ofα-glucosidase (yeast) andα-galactosidase (coffee beans), respectively.<