Non-Stick Sugars: Synthesis of Difluorosugar Fluorides as Potential Glycosidase Inactivators

Four new difluorosugar fluorides, 2-deoxy-2,5-difluoro-alpha-L-idopyranosyl fluoride, 1,5-difluoro-D-glucopyranosyl fluoride, 1,5-difluoro-L-idopyranosyl fluoride, and 2-deoxy-1,2-difluoro-D-glucopyranosyl fluoride, were synthesized from known precursors by a radical bromination/fluoride displacement sequence, followed by deprotection. The compounds were tested as time-dependent inactivators of the beta-glucosidase from Agrobacterium sp. (Abg, EC 3.2.1.21) and, while they were shown to bind to the enzyme active site as reversible competitive inhibitors, the only time-dependent inactivation observed was traced to the presence of an extremely small amount (<0.1%) of a highly reactive contaminating impurity.