Total asymmetric synthesis of (−)-conduramine B-1 and of its enantiomer. N-Benzyl derivatives of conduramine B-1 are β-glucosidase inhibitors

The 'naked sugars' (+)- and (-)-7-oxabicyclo[2.2.1]hept-5-en-2-one have been converted into (-)-conduramine B-1 ((-)3) and its enantiomer (+)-3, respectively. They have been condensed with a variety of aldehydes in the presence of NaBH(OAC)(3). The N-substituted derivatives 4 and ent-4 so-obtained have been tested against two alpha-glucosidases, two amyloglucosidases, two beta-glucosidases and one beta-xylosidase for their inhibitory activities. Although (-)-3 and (+)-3 do not inhibit any of these enzymes at 1 mM concentration, N-benzylated derivatives of (-)-conduramine B-1 are selective and competitive inhibitors of beta-glucosidases with K-i in low micromolecular range. (c) 2005 Elsevier Ltd. All rights reserved.