Synthesis of novel ammonium and selenonium ions and their evaluation as inhibitors of UDP-galactopyranose mutase.
The syntheses of two ammonium salts of 1,4-dideoxy-1,4-imino-d-galactitol containing erythritol sulfate side chains are described. The parent compound is a known inhibitor of the enzyme UDP-galactopyranose mutase (UDP-galactopyranose furanomutase, E.C. 5.4.99.9), which is responsible for the conversion of UDP-galactopyranose into UDP-galactofuranose and is presumably protonated in its active form. The side chain was chosen because it is present in a known sulfonium ion alpha-glucosidase inhibitor, salacinol. The syntheses of the selenonium analogues derived from 1,4-dideoxy-1,4-seleno-d-galactitol are also described. The synthetic strategy in the syntheses of all four salts involved the nucleophilic attack of a protected derivative of the alditol at the least hindered carbon of 2,4-O-benzylidene d- or l-erythritol-1,3-cyclic sulfate to give adducts that were subsequently deprotected. The importance of different protecting groups used in the various syntheses is also highlighted. Enzyme inhibition assays carried out on these compounds, and the corresponding sulfonium ions synthesized previously, show that they are poor inhibitors of UDP-galactopyranose mutase.
Veerapen
Natacha
N
Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
Yuan
Yue
Y
Sanders
David A R
DA
Pinto
B Mario
BM
D002236:Carbohydrate Conformation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005420:Flavoproteins / Q000037:antagonists & inhibitors; D007202:Indicators and Reagents; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors*; D007711:Klebsiella pneumoniae / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D009904:Optical Rotation; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D018036:Selenium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005420:Flavoproteins; D007202:Indicators and Reagents; D000644:Quaternary Ammonium Compounds; D018036:Selenium Compounds; D019751:Intramolecular Transferases; C098051:UDP-galactopyranose mutase