Synthesis of carba- and C-fucopyranosides and their evaluation as alpha-fucosidase inhibitors - Analysis of an unusual conformation adopted by an amino-C-fucopyranoside

Several carba- and C-fucopyranosides bearing a variety of substituents at t heir pseudoanomeric positions have been synthesized and tested as inhibitor s of bovine kidney a-fucosidase. From the IC50 values, some conclusions abo ut the structure-activity relationship could be drawn, The presence of a hy droxyl group close to the pseudoanomeric position, or the presence of an ar omatic ring as substituent, were beneficial for inhibitory activity. A 1-(R )-amino-phenylmethyl C-fucopyranoside, the activity of which increased 40 t imes when the pH was changed from 5.0 to 7.0, adopted a C-4(1) conformation , in contrast to the C-1(4) form normally adopted by natural fucopyranoside s. The conformation of this compound was analyzed in comparison with that o f the 1-(S)-configured epimer, using NMR spectroscopy and molecular modelin g.