N-α-Formyl-L-lysine

N-(1-Deoxy-D-fructos-1-yl)-L-amino acids (fructose amino acids), Amadori compounds, are formed by reaction of D-glucose and L-amino acids and Amadori rearrangement. They are detected in heat-processed natural products and various foodstuffs and are key products of the Maillard-Browning reaction. N-Nitroso-N-(1-deoxy-D-fructos-1-yl)-L-amino acids (N-NO-fructose amino acids), N-NO-Amadori compounds, are formed in high yields by reacting fructose amino acids with sodium nitrite in acidic aqueous solution. They constitute a new class of non-volatile, bis-beta-oxidized nitrosamine derivatives with unknown biological (mutagenic and/or carcinogenic) activity. N-NO-Fructose amino acids may be formed in nitrite-containing Maillard systems (e.g., cured-meat products, tobacco) or in the human stomach after ingestion of food containing fructose amino acids and nitrite in food or saliva. Thirteen fructose amino acids and 13 N-NO-fructose amino acids (-gly, -ala, -val, -leu, -ileu, -ser, -thr, -met, -asp, -pheala, -tyr, -his, -trp) were prepared and investigated by high-resolution 1H-nuclear magnetic resonance (NMR) and 13C-NMR spectroscopy. The percentage amounts of the sugar ring forms (beta-pyranose, beta-furanose, alpha-furanose and alpha-pyranose) of these compounds in D2O mutarotation equilibrium were determined by 13C-NMR spectroscopy, together with the amounts (%) of E/Z isomers in the case of N-NO-compounds. The nitrosation products of D-fru-L-tyr, D-fru-L-his and D-fru-L-trp were isolated and identified by spectroscopic methods (NMR, infra-red). The N-NO-fructose amino acids can be separated by reversed-phase, ion-pairing, high-performance liquid chromatography. In some case the E/Z isomers are separated.

Structure-reactivity relationships of Amadori rearrangement products compared to their related ketoses were derived from multiple NMR spectroscopic techniques. Besides structure elucidation of six Amadori rearrangement products derived from d-glucose and d-galactose with l-alanine, l-phenylalanine and l-proline, especially quantitative (13)C selective saturation transfer NMR spectroscopy was applied to deduce information on isomeric systems. It could be shown exemplarily that the Amadori compound N-(1-deoxy-d-fructos-1-yl)-l-proline exhibits much higher isomerisation rates than d-fructose, which can be explained by C-1 substituent mediated intramolecular catalysis. In combination with a reduced carbonyl activity of Amadori compounds compared to their related ketoses which results in an increased acyclic keto isomer concentration, the results on isomerisation dynamics lead to a highly significant increased reactivity of Amadori compounds. This can be clearly seen, comparing approximated carbohydrate milieu stability time constants (ACuSTiC) which is 1 s for N-(1-deoxy-d-fructos-1-yl)-l-proline and 10 s for d-fructose at pD 4.20 ± 0.05 at 350 K. In addition, first NMR spectroscopic data are provided, which prove that α-pyranose of (amino acid substituted) d-fructose adopts both, (2)C5 and (5)C2 conformation.

Heyns compounds, 2-carboxymethylamino-2-deoxy-D-glucose (1), -mannose (2), and -galactose (3), were prepared by N-carboxymethylation of the corresponding hexosamines and 1 was also prepared via the reaction of D-fructose with glycine. Both 1 and 3 crystallize from aqueous solutions as zwitterions in the alpha-pyranose form and in the 4C1 conformation. Crystalline 1 is nearly isostructural to N-acetylglucosamine, forming stacks of molecules with infinite chains of homodromic hydrogen bonds along the stacks. For both 1 and 3, all hydroxyl, ammonium, and carboxyl groups are involved in intermolecular hydrogen-bonding, and an intramolecular hydrogen bond in 3 is formed via interaction of the ammonium and carboxyl groups. 1H and 13C NMR spectra (D2O solutions) indicate that all of the compounds are conformationally unstable, and that the major form present in D2O solution at 25 degrees C is the 4C1 alpha-pyranose form, with the 4C1 beta-pyranose form present in lesser amounts. In addition, for solutions of 2 and 3, considerable amounts of alpha- and beta-furanose forms are present and exist in conformations favorable for a cis-relationship between the carboxymethylammonium and anomeric hydroxyl groups.