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

Abstract

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.