The endo‐ and exo‐Anomeric Effects in Furanosides. A Computational Study

Abstract

The anomeric effect is rarely studied in the context of furanoses. Owing to large flexibility of the furanose ring, its influence is inherently coalesced with those of other steric and stereoelectronic factors governing the conformation and other molecular properties of furanoses. In this article the energetic magnitude of the exo‐ and endo‐anomeric effects in furanose systems is reported for the first time for a series of different ring substituents. Our computational study, performed at the M062X/6‐31G(d) level of theory, was complemented by the “hybrid” quantum mechanics/molecular mechanics–molecular dynamics simulations. The results indicate that the energetic magnitude of the endo‐anomeric effect changes in the following order of ring substituents: ‐Br > ‐Cl > ‐F > ‐OCH3 > ‐SCH3 > ‐OH > ‐NH2 > ‐CN > ‐CH3. The corresponding energies are highly correlated with the analogous values calculated for pyranoses, but are systematically larger by, on average, 2.7 kJ/mol. Analogously to pyranoses, the exo‐anomeric effect acts toward stabilization of the gauche+ or gauche‐rotamers for the axially‐ or equatorially‐oriented exocyclic, rotatable groups, respectively. However, the energy contributions to those rotamers differ between furanoses and pyranoses and are dependent on the substituent orientation.