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Abstract
The reaction of weakly basic aromatic amines with aldehydic groups of reducing monosaccharides like glucose under acidic aqueous conditions resulted in the reversible formation of glycosylamines. The primary objective of this work was to determine the kinetics and mechanisms of this reaction using model aromatic amines like kynurenine, 2'-aminoacetophenone and daptomycin with glucose and other monosaccharides.
Reactions of kynurenine and 2'-aminoacetophenone were conducted in the presence of glucose in the pH range of 1 to 6.5 at 40°C in dilute hydrochloric acid or buffer solutions. Reaction products were separated using RP-HPLC and identified using LC-MS, UV spectroscopy and NMR spectroscopy. A simple reversible scheme describing the kinetics was used to estimate rate constants. An underlying chemically-based scheme which described the reversible formation of the glycosylamines from the reaction of aromatic amines and glucose via an imine intermediate was correlated to the observed rate constants to demonstrate that the formation and breakdown of the imine were the critical steps in glycosylamine formation and hydrolysis, respectively. pH rate profiles for imine formation were consistent with three major pathways: specific and general acid catalysis and solvolytic attack. The pH rate profiles for all model aromatic amine compounds displayed inflections in the pH range of 4--5 which were consistent with a change in rate determining step from the addition of the amine to the carbonyl carbon to dehydration of the tetrahedral intermediate associated with imine formation. Nonlinear buffer plots in the pH range of 4--5 confirmed the existence of a change in rate determining step. The addition of kynurenine to glucose followed two concurrent mechanisms; a concerted mechanism and a stepwise mechanism, unlike the other amines that predominantly followed a concerted mechanism for addition.
