A C ‐linked Glycomimetic in the Gas Phase and in Solution: Synthesis and Conformation of the Disaccharide Manα(1,6)‐ C ‐ManαOPh

The effect of carbon is subtle but sweet : The flexible C‐linkage in the newly synthesised C ‐glycosyl mimetic, Manα(1,6)‐ C ‐ManαOPh allows OHπ bonding, both in the gas phase and in aqueous solution. This interaction is absent in the O‐linked disaccharide (see figure).The intrinsic conformational preference of a newly synthesised glycomimetic, the C‐ linked disaccharide Manα(1,6)‐ C ‐ManαOPh ( 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 Manα(1,6)‐ C ‐ManαOMe ( 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 1 which adopts a conformation (not populated in 2 ) with glycosidic dihedral angles ( ϕ , ψ , ω ) of −72°, 52° and 66°; supported in part by an OHπ hydrogen bond. This conformer is also strongly populated in an aqueous solution of 1 (and very weakly, of 3 ) together with a second conformer, with dihedral angles ( ϕ , ψ , ω ) of about −60°, 180° and 60°, not seen in the gas phase but by far the dominant conformer in an aqueous solution of 3. The C ‐disaccharide 1 was tested as a potential inhibitor, but displayed no significant inhibitory activity against Jack Bean α‐mannosidase.