A C-linked Glycomimetic in the Gas Phase and in Solution: Synthesis and Conformation of the Disaccharide Man alpha(1,6)-C-Man alpha OPh

The intrinsic conformational preference of a newly synthesised comimetic, the C-linked disaccharide Man alpha(1,6)-C-Man alpha OPh(1), has been determined in the gas phase at about 10 K by infrared ion dip spectroscopy Coupled with density functional theory and ab initio calculations, and compared with its dynamical conformation in aqueous solution at 298 K by NMR spectroscopy. Comparisons are also made between these conformations and those of the corresponding O-linked disaccharide 2 in the gas phase and the C-linked disaccharide Man alpha(1,6)-C-Man alpha OMe (3) in the gas phase and in aqueous solution. The C- and O-linked disaccharides 1 and 2 present quite distinct conformational preferences in the gas phase: inter-glycosidic hydrogen bonding, seen in one of the two conformers populated in 2, is not seen in I which adopts a conformation (not populated in 2) with glycosidic dihedral angles (phi, psi, omega) of -72 degrees, 52 degrees and 66 degrees; supported in part by an OH-pi hydrogen bond. This conformer is also strongly populated ill all aqueous Solution Of I (and very weakly, of 3) together with a second conformer. with dihedral angles (phi, psi, omega) of about -60 degrees, 180 degrees and 60 degrees, not seen in the gas phase but by far the dominant conformer in an aqueous Solution of 3. The C-disaccharide I was tested as a potential inhibitor, but displayed no significant inhibitory activity against Jack Bean alpha-mannosidase.