Perfluoroalkylation of Nitrones for the Synthesis of a Series of Fucosidase Inhibitors

Fucosidase inhibitors represent captivating targets for various biological applications. Iminosugars featuring a fluoroalkyl chain in the pseudoanomeric position were synthesized by nucleophilic addition of a perfluoroalkyl Grignard reagent to a nitrone. Reduction of the N–O bond of the hydroxylamine was achieved by treatment with an aqueous solution of sulfur dioxide. The pKa = 4.5 of the target pyrrolidine reflected a strong electronic effect of the fluoroalkyl chain. Inhibitory potencies of the fluorinated iminosugars and their corresponding hydroxylamines were evaluated against α‐L‐fucosidase at various pH values. Iminosugars featuring a fluoroalkyl chain in the pseudoanomeric position are synthesized by nucleophilic addition of a perfluoroalkyl Grignard reagent to a nitrone. Reduction of the N–O bond of the hydroxylamine is achieved by treatment with aqueous SO2. Inhibitory potencies of the fluorinated iminosugars and their corresponding hydroxylamines are evaluated against α‐L‐fucosidase at various pH values.