Pyranose ring puckering in aldopentoses, ketohexoses and deoxyaldohexoses. A molecular dynamics study

Conformation of monosaccharides, including the ring shape, has for years been the subject of intensive research. Although d-aldohexopyranoses are the most extensively studied pyranoses, there also exist other groups of saccharides that contain analogous chemical system of the six-membered ring. Here we describe in details the results of the molecular dynamics-based conformational analysis concerning a series of pyranoses, namely: d-aldopentoses, d-ketohexoses as well as deoxy- (d-quinovose, l-fucose, l-rhamnose) and dideoxy- (abequose, paratose, tyvelose, digitoxose) derivatives of aldohexoses. By using the carbohydrate-dedicated GROMOS 56a6_CARBO force field, we determined the conformational properties of both the lactol and hydroxymethyl groups as well as the anomeric populations for all considered compounds. The orientation of the lactol group follows the trend expected on the basis of the exo-anomeric effect for all compounds whereas the conformation of the hydroxymethyl group in d-ketohexoses is represented by the two gauche (with respect to the ring oxygen atom) rotamers. The special emphasis is put on the ring-inversion properties studied in the context of both the full chair-chair inversion and the chair-boat/skew-boat rearrangement. The calculated ring-distortion energies, compared with those obtained for regular d-aldohexopyranoses allowed for estimating the influence of particular substituents on the ring flexibility. Overall, such influence is correlated with the dimension of the substituent and its orientation but is limited to the case of the chair-chair inversion whereas the chair-to-boat/skew-boat rearrangement exhibits roughly the same properties for all pyranoses. For all d-aldopyranoses the α anomers exhibit lower ring-inversion free energies in comparison to the β anomers whereas this trend is inverted in the case of d-ketohexopyranoses.