Mechanistic Studies on the Formation of Pyrroles and Pyridines from [1- 13 C]-D-Glucose and [1- 13 C]-D-Arabinose

The Maillard reaction of [1-13C]-D-glucose and [1-13C]-D-arabinose with 4-aminobutyric acid (representing peptide bound lysine as well as a Strecker inactive amino acid) and L-isoleucine (representing a Strecker active amino acid) was investigated to get more insight into the reaction pathways involved. The extent and position of the labeling were determined by MS data. The results support 3-deoxyaldoketose as intermediate of N-alkyl-2-formyl-5-hydroxymethyl- and N-alkyl-2-formyl-5-methylpyrroles (1, 3, 7, 9) and disqualify 4-deoxy- and 1-deoxydiketose routes to N-alkyl-2-hydroxyacetyl- and N-alkyl-2-acetyl-pyrroles (2, 4, 8, 10), respectively. The 1, 3-dideoxy-1-amino-2, 4-diketose C is postulated as a new key intermediate in the formation route to 2, 4, 8, and 10 from D-glucose. In addition, this β-dicarbonyl route is correlated to the 3-deoxy-aldoketose route by keto-enol tautomerism as demonstrated by Maillard experiments in deuterium-oxide. The D-exchange ratios of compounds 1, 3, 7, 9, 13, and 14 (which were examined by MS- and 1H NMR spectroscopy) indicated incorporation of D-atoms at C4 of glucose. The β-dicarbonyl pathway of [1-13C]-D-glucose/L-isoleucine (glycine) Maillard experiments generates 2-acetyl-[5-13C]-pyrrole and 2-methyl-3-[6-13C]pyridinol via a Strecker active intermediate. Based on the results of these labeling experiments and on the results of Maillard experiments in deuteriumoxide a revised scheme of the Maillard reaction of D-glucose with amines and α-amino acids is presented.