Total asymmetric synthesis of (-)-conduramine B-1 and of its enantiomer. N-Benzyl derivatives of conduramine B-1 are beta-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 1mM concentration, N-benzylated derivatives of (-)-conduramine B-1 are selective and competitive inhibitors of beta-glucosidases with K(i) in low micromolecular range.
Łysek
Robert
R
Laboratoire de Glycochimie et de Synthèse Asymétrique, Ecole Polytechnique Fédérale de Lausanne (EPFL), ISIC, BCH, CH-1015 Lausanne-Dorigny, Switzerland.
Schütz
Catherine
C
Vogel
Pierre
P
D001234:Aspergillus niger / Q000201:enzymology; D001421:Bacteria, Anaerobic / Q000201:enzymology; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D044602:Cellulases / Q000037:antagonists & inhibitors*; D053138:Cyclohexenes; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006595:Hexosamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D027861:Prunus / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014995:Xylosidases / Q000037:antagonists & inhibitors*
D001643:Bridged Bicyclo Compounds; D053138:Cyclohexenes; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D006595:Hexosamines; C030791:valienamine; D044602:Cellulases; D014995:Xylosidases; C026579:exo-1,4-beta-D-xylosidase