Carbohydrate Reaction Intermediates:  Effect of Ring-Oxygen Protonation on the Structure and Conformation of Aldofuranosyl Rings

Abstract

The effect of ring-oxygen protonation on the structure and conformational properties of a model deoxyaldofuranose, 2-deoxy-β-d-glycero-tetrofuranose 2, has been examined with the use of NMR spectroscopy and ab initio molecular orbital calculations conducted at the HF/6-31G* level of theory. The computational method was validated by comparing the conformational behavior of 2 derived from PSEUROT treatment of 3 J HH values measured in 2 (2H2O solvent) with that predicted from the theoretical calculations. Coupling data indicate that 2 favors S forms in solution (∼89% 4T3, ∼11% E2), while MO data indicated more comparable populations of the same or very similar N and S forms. Protonation of 2 at the ring oxygen (O4), yielding 1, gave two distinct protonated forms which differed in the orientation of the proton about O4. Both forms showed substantial changes in ring structure and conformation compared to 2. Protonated forms almost exclusively prefer S forms (E3), and energy barriers for N/S interconversion were found to be considerably higher than those for 2, leading to the conclusion that 1 is more conformationally constrained than 2. Bond lengths in the vicinity of O4 changed significantly upon conversion of 2 to 1; for example, the C1−O4 bond length increases by ∼14%, the C1−H1 and C1−O1 bond lengths decrease by 1−5%, and the C4−O4 bond length increases by ∼5%. These results indicate that O4 protonation predisposes 2 toward ring opening by inducing specific structural and conformational modifications, thus providing a more concise explanation of the role of acid catalysis in furanose anomerization (i.e., 1 resembles the transition state of the acid-catalyzed anomerization reaction more than 2). The molecular orbital data obtained in this investigation also provide evidence for a new structural factor (a 1,3-effect involving oxygen lone-pair orbitals) that influences bond lengths in carbohydrates.

Thermodynamics of the Interaction of HCl withd-Fructose in Water at 278.15−318.15 K

“…In the recent paper, we suggested a so-called “H + -induced structural change” model to explain the differences in interaction between HCl−glucose and HCl−alcohol pairs. This model has been further confirmed by the very recent study of Serianni and colleagues . On the basis of this model and the hydration model of sugars mentioned above, we can easily understand why the decyclization of sugar will contribute a positive value to g EN , h EN , and Ts EN .…”

13C−1H and 13C−13C Spin-Coupling Constants in Methyl β-d-Ribofuranoside and Methyl 2-Deoxy-β-d-erythro- pentofuranoside: Correlations with Molecular Structure and Conformation

“…, the interaction of lone-pair orbitals on O3 with the C4−H4 bond) also affect C−H bond lengths in a consistent fashion. These latter interactions, when present, appear to cause bond shortening , and this effect is discussed in a recent report …”

“…Vicinal lone-pair effects (e.g., the interaction of lone-pair orbitals on O3 with the C3-H3 bond) appear to be substantial, with antiperiplanar arrangements causing bond lengthening as reported previously. 27,28,[50][51][52] In addition, recent studies 72 suggest that 1,3-interactions between oxygen lone-pair orbitals and C-H bonds (e.g., the interaction of lone-pair orbitals on O3 with the C4-H4 bond) also affect C-H bond lengths in a consistent fashion. These latter interactions, when present, appear to cause bond shortening, and this effect is discussed in a recent report.…”

“…These latter interactions, when present, appear to cause bond shortening, and this effect is discussed in a recent report. 72 Thus, it appears that C-H bond orientation, while important, may not be the sole determinant of C-H bond length in aldofuranosyl rings.…”

Deuterium Nuclear Spin–Lattice Relaxation Times and Quadrupolar Coupling Constants in Isotopically Labeled Saccharides

“…4), it is important to appreciate that these bond lengths will be significantly affected by vicinal lone-pair (35), 1,3-lone-pair (36), and 1,4-lone-pair (33) effects in saccharides. Thus, for example, rotation of C-O bonds on carbons bearing deuterons changes the disposition of oxygen lone-pairs with respect to the C-2 H bond, thereby changing its length and, indirectly, affecting the magnitudes of 1 J CH and 2 H NQCC values.…”