The Proton Magnetic Resonance Spectra and Tautomeric Equilibria of Aldoses in Deuterium Oxide

Abstract

The proton magnetic resonance spectra of D-sylose, D-lyxose, n-arabinose, D-ribose, D -~~L I C O S~, n-mannose, and D-galactose were determined a t 100 Mc.p.s. in deuteriu~ri oxide. 'I'he chemical shifts and structures of a number of ring protons in these compounds were determined either by spin-deco~~pling experiments or by synthesis of specifically deuterated compounds. 'I'he proton magnetic resonance parameters are shown to provide considerable information on the conformations and tautonleric equilibria for the sugars in aqueo~ls solution. I t is concluded that, for aldoppranoses in a chair conformation, the chemical shift of equatorial protons a t a given position is virtually independent of configurational changes a t other positions. However, an axial proton is shielded about 0.3 p.p.111. less by an axial hydrosyl group a t a neighboring position than when the hydroxyl group is in an equatorial orientation. An axial hydrosyl group leads to deshielding of a n opposing axial proton b y about 0.35 p.p.m. By using the chemical shifts of the ring protons of @-D-xylopyranose and @ -D -~~u c o~~~~I I o s~ as reference point, the chernical shifts of protons in other pyranose structures could be anticipated to within a useful . . degree of accuracy.Lvidence was obtained that D-ribose and 2-deoxv-D-ribose esist in aqueous s o l u t i o~~ both in the pyranose and in the furanose forms. None of the other pentoses showed readily detectable anlounts of the furanose forrns a t equilibrium. rllthough D-allose does not give readily detectable alnounts of the furanose forms \vhen a t equilibriunl in aqueous solutions, n-altrose does. D-Talose showed only two forms, one of which was the @-pyranose structure.Lenz and Heeschen (I) examined the nuclear magnetic resonance (n.111.r.) spectra of D-glucose, D-mannose, 2-deoxy-D-glucose, and D-xylose with deuterium oxide as solvent. Only the signals of the anomeric protons were readily observed, and the spacings of these signals were used as coupling constants to estiillate conformational features for these sugars in aqueous solution. The observed spacings \\rere undoubtedly strongly influenced by virtual long-range coupling (2, 3) and, therefore, were not a direct measure of the coupling constants involved. Also, it is now evident (4, 5) that the relationship bet~veen the coupling constant and the dihedral angle defined by neighboring protons (the Ixarplus relationship) is subject to parameters other than the dihedral angle. Therefore, attempts to relate the spacings of the doublet signals for the anomeric protons of sugars t o precise molecular geometry are without either a theoretical or an empirical basis. Althougll coupling constants between neighboring protons cannot be used to predict precise conformational features, their use in appropriate instances for establishing configurationa1 features (6) remains unchallenged.Use has also been made of chemical shifts for establishing the configurations of sugars

Isotopically-enriched carbohydrates: The preparation of [2H]-enriched aldoses by catalytic hydrogenolysis of cyanohydrins with 2H2

“…Assignments of 13C chemical shifts have been made using [2H]-enriched carbohydrates based on the disappearance of the resonance arising from the carbon directly bound to the deuteron and on the upfield shifts experienced by carbon nuclei and y to the deuteron (1-4). The interpretation of complex 'Hmr spectra can also be aided by deuteration (5,6). The use of [13C]-enriched aldoses, aminoaldcses, and aldose phosphates permitted the unequivocal assignment of carbon chemical shifts, determination of 13C-H and 13C-13C coupling constants, and the in ~i f r o monitoring of enzyme-catalyzed conversions (7)(8)(9)(10)(11)(12).…”

“…The preparation of [2N]-enriched carbohydrates is most often accomplished by reduction of carbonyl derivatives with NaB2H, (4,5). This approach is limited by the availability of the appropriate carbonyl.…”

Pyranose–furanose and Anomeric Equilibria: Influence of Solvent and of Partial Methylation

“…Thus, 2,3-di-0-methyl-D-arabinose (I) shows a considerably higher content of furanose in solution than does D-arabinose itself. In deuterium oxide, I produces a t least three H-1 signals, whereas only two significant ones are found for arabinose (1,2). Although unequivocal assignments have not been made, the intensity of the weakest signal shows that a minimum of 17% of furanose is present in the solution of I.…”

“…Sugars having the xylo or lyxo configuration appear t o exist almost exclusively as pyranoses both in water (2,9) and in dimethyl sulfoxide (1) ; accordingly, each exhibits only two anomeric proton or hydroxyl proton signals (see belo\\-, honyever, for an additional comment on D-lyxose). This overwhelmingly greater preference for the pyranose form is also apparent with 2,3-di-0-methyl-D-xylose, 2,3-di-O-n1ethyl-~-gl~1cose, and 2,3-di-0-methyl-D-mannose, each of which sho~vs only two OH-1 signals4 ~vhen equilibrated in dimethyl sulfoxide.…”

Benzylic substitution in ring A of daunomycinone. Conversion of daunomycinone into thiodaunomycinone and related deoxy analogs

“…The 7R configuration of 9 was determined from the benzylic proton (H-7) which was shown as a multiplet at 6 5.077 having vll2 15.9 Hz, in agreement with an axial orientation of H-7. The stereochemistry at position 7 for compounds 8 and 9 can be ascertained on the basis of the chemical shifts in pyranoid rings (28)(29)(30); equatorial protons resonate at lower field than constitutionally similar axial protons. The benzylic proton H-7 for compound 8 was shown at relatively lower field (6 5.447) than that for compound 9 (6 5.077).…”