C-Disaccharides as carba analogs of "natural" O-disaccharides are non-hydrolyzable carbohydrate mimics that could affect biosynthesis of glycoproteins and/or intercell communication and thus might have therapeutic use.
Conformational behavior of four 1,3-C-disaccharides of general formulae 1 and 2 containing D-glucopyranose or D-mannopyranose moiety at the non-reducing end and D-or L-2-deoxy-arabino-hexopyranoside or D-or L-mannopyranoside moiety, respectively, was studied using various computational methods based on molecular mechanics (MM) (ref.1) as well as ab initio/DFT calculations. Systematic mapping of conformational space was performed using the older MM3(96) forcefield and the resulting Ramachandran Φ, Ψ plots were compared with the plots obtained from molecular dynamic runs (GLYCAM06 and OPLS_2005 forcefields) with explicit solvents (water or methanol). For both MM methods, experimental NMR vicinal couplings around the pseudoglycosidic bond were compared with the calculated ones which were derived from the appropriate torsions using the Karplus equation. Alternatively, vicinal coupling constants 3JHH were calculated at the BHandH/IGLO-II level from 200 solute solvent clusters selected from MD snapshots, augmented with CPCM solvation and normal mode optimized.
Our results confirm that orientations around C-glycosidic bond are governed by the exo-anomeric effect and are very similar to each other for the studied compounds. Conformational preferences around C-aglycone bond, however, differ substantially and are controlled by 1,3-diaxial-like interactions and other effects.
References
1. Vích O., Kniežo L., Dvořáková H., Raichi I., Valenta Š.: Collect. Czech Chem. Commun. 2005, 70, 2086.
Acknowledgement
This work was supported by the Ministry of Education of the Czech Republic, project MSM6046137305.
