Absence of Reverse Anomeric Effect in Furanosides

Abstract

A series of conformationally restricted N-"furanosides" has been synthesized, where the carbons of the tetrahydrofuran ring are kept in one plane by a rigid norbornane skeleton, permitting only the ring oxygen to move above or below the tetrahydrofuran ring plane. This causes the substituents of the anomeric carbon to occupy a pseudoaxial or a pseudoequatorial position. On protonation of these "norbornane-furanosides" with trifluoromethanesulfonic acid, all three compounds exhibited decreasing coupling constants for the anomeric proton, indicating a shift toward the pseudoaxial conformation. The coupling constant measurements were supported by volume integration of NOESY cross-peaks, which also showed a change toward the pseudoaxial conformation upon protonation of the nitrogen. These results provide no evidence for the so-called reverse anomeric effect; on the contrary they are in full agreement with a small normal anomeric effect.

Differential reactivity of α and β 2′-deoxyribonucleosides towards protonation and metalation

“…In furanoses similar to the ones discussed in this work, an inverse anomeric effect has recently been excluded[39].…”

Conformational effects in sugar ions: spectroscopic investigations in the gas phase and in solution

“…[2][3][4][5] Subsequent investigations explored its theoretical basis to distinguish between cause and effect, through semi-empirical and ab initio calculations, 6,7 but many others questioned its realityand its definition. [8][9][10][11][12][13][14][15][16] Perrin et al for example, 11 discussed two different measures of the RAE, one based on the equilibrium between the normal ( 4 C 1 ) and inverted ( 1 C 4 ) conformers of the a anomer; the other on the equilibrium between the a and b anomers of the 4 C 1 conformers, which forms the basis for the definition of the normal anomeric effect. Based on the second measure and comparing solution equilibria between the a and b anomers of a series of D-glucosylamines 10 and subsequently, N-(glycopyranosyl) imidazole 12 and aniline 13 derivatives, Perrin et al found no evidence for a reversal of the normal anomeric effect.…”

The Problem of Origins and Origins of the Problem: Influence of Language on Studies Concerning the Anomeric Effect

“…[64] Is the RAE operative in other systems? [65] Does the RAE behave as as ynthetic control element? [66] If the RAE model is agood one,then these questions are meaningful, and dedication of mental and physical resources to their elucidation is productive.B ut in the more parsimonious scenario in which no RAE exists,these inquiries are distracting.…”