A short and flexible route to aza-beta-(1 -> 6)-C-disaccharides: Selective alpha-glycosidase inhibitors
The syntheses of azaMan-beta-(1-->6)-C-Glc (4), azaGlc-beta-(1-->6)-C-Glc (5), and azaGal-beta-(1-->6)-C-Glc (6) based upon double reductive amination of acetylenic carbohydrate-derived diketones is described. The required diketones are obtained by addition of the acetylenic sugar anion derived from dibromoolefin 7 to benzyl-protected mannopyranolactone, glucopyranolactone, or galactopyranolactone, followed by reduction of the ketose and oxidation of the resulting diol. Ensuing double reductive amination and hydrogenolysis affords the target compounds in reasonable to good yields. Enzyme inhibition tests show that neither of the three compounds 4, 5, and 6 inhibit beta-glycosidases, while moderate to good inhibitory activities were found on alpha-glycosidases, the most active being 6 (alpha-galactosidase: K-i = 0.092 mu M).
Keywords: carbohydrates ; aza sugars ; double reductive amination ; enzyme ; inhibitors ; glycosidase inhibitors ; Aza-c-disaccharides ; biological evaluation ; reductive amination ; castanospermine ; glucosidase ; homonojirimycin ; swainsonine
Leiden Inst Chem, NL-2300 RA Leiden, Netherlands. Univ Lausanne, Chim Sect, BCH, CH-1015 Lausanne, Switzerland.
Record created on 2005-11-09, modified on 2016-08-08