Glycosylation of aromatic amines II: Kinetics and mechanisms of the hydrolytic reaction between kynurenine and glucose

✍ Scribed by Madhushree Y. Gokhale; Lee E. Kirsch

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 226 KB
• Volume: 98
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.21754

✦ Synopsis

The kinetics of the weakly basic aromatic amine, kynurenine, with glucose were studied as model reactants aimed at mechanistic understanding of pharmaceutically relevant amine-aldehyde reactions. The reaction kinetics of the forward and reverse processes (glycosylamine formation and hydrolysis) were studied under firstorder conditions in aqueous solutions at 408C in the pH range 1-6.5 in the presence of various buffers. The a-and b-glycosylamines were reversibly formed via an acyclic imine that was not present in detectable quantities. Rate-limiting formation of the imine was complex and involved the addition of the amine and aldehyde to form the carbinolamine followed by the acid-catalyzed dehydration to the imine. The pH-rate profile was characterized by three kinetically distinguishable processes. At lower pH values, the profile was consistent with specific acid-catalyzed rate-determining addition of amine and aldehyde. In the pH range of 4-6 a downward bend was attributable to the change in rate determining step from addition to dehydration. In the pH region of 2-3 the rate law was described by specific acid catalysis and solvolysis of the zwitterionic form of kynurenine. Nonlinear buffer effects and Bro ¨nsted plots were shown to be consistent with this interpretation of the pH-rate profile.