J-COUPLING ANALYSIS AS A MEANS FOR STEREOCHEMICAL ASSIGNMENTS IN FURANOSIDES

The widespread use of coupling constant information for stereochemical assignment in pyranosides is based on the conformationally rigid six-membered ring they contain. For most pyranosides, one of the two possible chair conformations is largely predominant at room temperature, and this allows an easy discrimination between the large axial-axial couplings and the small axial-equatorial and equatorial-equatorial couplings. This is not the case for furanosides, where the flexibility of the five-membered ring (leading to the so called pseudorotation) causes large variations in coupling constants between conformers, which prevent such an easy correlation between coupling constant values and relative configuration of adjacent carbon atoms. As a consequence, stereochemical elucidation of furanosides is usually based on NOESY/ROESY correlations and/or chemical degradation. As a matter of fact, some correlation between vicinal couplings and relative configuration of furanosides is present in the literature. As early as in 1963, in a paper reporting the proton NMR spectra of all methyl pentofuranosides, it was clearly recognized that a "small" vicinal coupling in a furanoside implies that the coupled protons are trans oriented. However, this principle has been used in the subsequent structure elucidation work only sporadically, and, even then, in a way that resembles much more the empirical comparison with a model compound than the application of a general rule. The reason for this is probably that the threshold below which a coupling constant can be considered "small" has never been defined, making the practical application of this principle difficult. To clarify this point, we undertook an in-depth computational study of coupling constants of furanosides, and showed that in furanosides a vicinal coupling constant < 2.0 Hz (for H-1/H-2 or H-3/H-4) or < 3.5 Hz (for H-2/H-3) can be considered a proof of the trans orientation of the relevant protons.