Synthesis of all-cis 2,5-imino-2,5-dideoxy-fucitol and its evaluation as a potent fucosidase and galactosidase inhibitor

We here describe a simple and efficient synthetic method for a non-hydrolysable precursor of a GDP-fucose analogue: The synthesis of the racemic aminofuranofucitol 3 from sorbic alcohol by nitroso-Diels–Alder reaction. This ‘all-cis-pyrrolidine’, with all substituents occupying a cis position, has been determined as a potent inhibitor of α-l-fucosidase and a moderate inhibitor of α- and β-d-galactosidase. The good recognition of this fucose moiety analogue by specific enzymes is thus confirmed. The C-anomeric bond in this particular structure is in the β-position and makes this compound an interesting candidate for further chemical modifications. Influence of the methyl and hydroxymethyl groups on the inhibition potency is discussed.

Graphical abstractWe describe the synthesis of the racemic aminofuranofucitol 3 from sorbic alcohol by nitroso-Diels–Alder as template for the synthesis of GDP-fucose analogues. Evaluation of this pyrrolidine as potent fucosidase and galactosidase inhibitor is discussed.Figure optionsDownload full-size imageDownload as PowerPoint slide