Fluorinated piperidine iminosugars and their N-alkylated derivatives: Synthesis, conformational analysis, immunosuppressive and glycosidase inhibitory activity studies. Issue 8 (22nd February 2018)

• Record Type: Journal Article
• Authors: Bhuma, Naresh; Burade, Sachin S.; Louat, Thierry; Herman, Jean; Kawade, Sonali; Doshi, Pooja J.; Dhavale, Dilip D.
• Is Part Of: Tetrahedron. Volume 74:Issue 8(2018)
• Page Start: 852
• Page End: 858
• Publication Date: 2018-02-22
• Subjects: Iminosugars -- Conformational analysis -- Immunosuppressive activity -- Glycosidase inhibitory activity; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2017.12.059
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The fluorinated piperidine iminosugars2a-4a and their N -octyl and N -decyl derivatives2b, c-4b, c were synthesized fromd -mannose/d -xylose using nucleophilic fluorination as the key step. The conformation of iminosugars2 /3, either 2 C 5 or 5 C 2, was assigned based on the 1 H NMR studies at different pH. Immunomodulatory activity of2a, c-4a, c was examined using Mixed Lymphocyte Reaction (MLR) and B-cell assay. The N -alkylated fluorinatedd - manno -iminosugars3b/4b were found to be better immunosuppressive agents (IC50 = 5–6 μ M) on T-cells. The fluorinated iminosugar3a/4a act as potent and selective inhibitors of β -glucosidase (IC50 = 4–8 μ M). The N -alkyl-iminosugars4b-c were found to be moderate inhibitors of α -glucosidase (yeast) and α -galactosidase (coffee beans), respectively. Graphical abstract: Highlights: Synthesis of mono- and gem-difluorinated piperidine iminosugars and their N-octyl and N-decyl derivatives in a less number of steps. Introduction of mono- and gem di-fluorine achieved by using DAST (nucleophilic fluorinataing agent) in high yields. Conformation of iminosugars, either 2 C 5 or 5 C 2, was assigned based on the 1 H NMR studies at different pH. Immunosupressive activity evaluated in vitro by MLR assay and B-cell assay. Glycosidase inhibitory activity study of mono- and gem-difluorinated piperidine-iminosugars is described.