Molecular and crystal structure of N-(2-deoxy-D-aldohexos-2-yl)-glycines (Heyns compounds)

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 C-4(1) 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. H-1 and C-13 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 4C(1) alpha-pyranose form, with the C-4(1) 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.