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 α-glucosidases, two amyloglucosidases, two β-glucosidases and one β-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 β-glucosidases with Ki in low micromolecular range.

Graphical abstractAlthough conduramine B-1 is not an inhibitor of β-glucosidases, N-benzyl derivatives inhibit these enzymes with Ki in low micromolar range. For 4i: Ki (β-glucosidase from almond) = 8 μM (competitive).Figure optionsDownload full-size imageDownload as PowerPoint slide