Fluorinated piperidine iminosugars and their N-alkylated derivatives: Synthesis,conformational analysis,immunosuppressive and glycosidase inhibitory activity studies |
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Authors: | Naresh Bhuma Sachin S. Burade Thierry Louat Jean Herman Sonali Kawade Pooja J. Doshi Dilip D. Dhavale |
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Affiliation: | 1. Department of Chemistry, Garware Research Centre, Savitribai Phule Pune University (Formerly University of Pune), Pune, 411007, India;2. KU Leuven, Interface Valorisation Platform (IVAP), Kapucijnenvoer 33, 3000, Leuven, Belgium;3. Department of Bio-Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Pune, 411007, India;4. Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven, 3000, Leuven, Belgium |
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Abstract: | The fluorinated piperidine iminosugars 2a-4a and their N-octyl and N-decyl derivatives 2b,c-4b,c were synthesized from d-mannose/d-xylose using nucleophilic fluorination as the key step. The conformation of iminosugars 2/3, either 2C5 or 5C2, was assigned based on the 1H NMR studies at different pH. Immunomodulatory activity of 2a,c-4a,c was examined using Mixed Lymphocyte Reaction (MLR) and B-cell assay. The N-alkylated fluorinated d-manno-iminosugars 3b/4b were found to be better immunosuppressive agents (IC50?=?5–6?μM) on T-cells. The fluorinated iminosugar 3a/4a act as potent and selective inhibitors of β-glucosidase (IC50?=?4–8?μM). The N-alkyl-iminosugars 4b-c were found to be moderate inhibitors of α-glucosidase (yeast) and α-galactosidase (coffee beans), respectively. |
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Keywords: | Iminosugars Conformational analysis Immunosuppressive activity Glycosidase inhibitory activity |
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