Acyclic forms of [1-C-13]aldohexoses in aqueous solution: Quantitation by C-13 NMR and deuterium isotope effects on tautomeric equilibria

High-resolution C-13 NMR spectra (150 MHz) have been obtained on the comple te series of D-aldohexoses (D-allose 1, D-altrose 2, D-galactose 3, D-gluco se 4, D-gulose 5, D-idose 6, D-mannose 7, D-talose 8) selectively labeled w ith C-13 at C1 in order to detect and quantify the percentages of acyclic f orms, and to measure and/or confirm percentages of furanoses and pyranoses, in aqueous solution. Aldehyde and hydrate signals were detected for all al dohexoses, and percentages of these forms at 30 degrees C ranged from 0.006 to 0.7% (hydrate) and 0.0032 to 0.09% (aldehyde). Aldehyde percentages are largest for the altro, ido, and talo configurations, ranging from 0.01 to 0.09%; the ido configuration yielded the most hydrate (0.74%). Hydrate/alde hyde ratios vary with aldohexose configuration, ranging from 1.5 to 13, wit h gluco exhibiting the smallest ratio and gulo the largest. H-2 Equilibrium isotope effects (EIEs) on aldohexose anomerization were measured in D-gala ctose 3 and D-talose 8 selectively C-13- and H-2-labeled at C1 and H1. The H-2 isotope effect on C-13 chemical shift, and broadband H-1- and H-2-decou pling, were exploited to permit simultaneous observation and quantitation o f the protonated and deuterated molecules in NMR samples containing equimol ar mixtures of D-[1-C-13] aldose and D-(1-C-13; 1-H-2] aldose. Small H-2 El Es were observed for 8, but were undetectable for 3. These results suggest that configuration at C2 influences the magnitude of the H-2 isotope effect at H1 and/or that the observed effect cannot be reliably interpreted due t o complications arising from the involvement of acyclic aldehyde forms as i ntermediates in the interconversion. of cyclic forms. The observed H-2 isot ope effects on aldohexose tautomeric equilibria provide new insights into t he important question of whether H-2 substitutions can alter aldofuranose r ing conformation, and lead to the identification of an optimal H-2- and C-1 3-substituted 2-deoxyribofuranose isotopomer on which to investigate this p otential effect.