Glycosylation of aromatic amines III: Mechanistic implications of the pH-dependent glycosylation of various aromatic amines (kynurenine, 2′-aminoacetophenone, daptomycin, and sulfamethoxzaole)

Abstract

Glycosylation reaction kinetics of a series of aromatic amines (kynurenine, 2′-aminoacetophenone, daptomycin, and sulfamethoxazole) was compared to propose a unifying reaction mechanism. Kinetic studies were conducted in aqueous solutions containing glucose in the pH range 1–6.5 with 2′-aminoacetophenone and daptomycin. The resultant pH-rate profiles were compared to previously reported profiles for the reactions of glucose and kynurenine or sulfamethoxazole. Glycosylation of weakly basic aromatic amines involved the addition of the unprotonated amine to the aldehydic sugar leading to carbinolamine formation followed by specific acid catalyzed dehydration. All of the pH-rate profiles displayed characteristic downward bend at pH 4–5 due to a change from rate-determining addition to dehydration. In the pH-rate profile for kynurenine, a second downward bend was observed in the pH region 2–4. This feature was absent for the other substrates and was attributed to differences in reactivity of the two ionization states of the alpha carboxylic acid in kynurenine. This stabilization was not possible for the other amines studied. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4639–4649, 2009