A C-linked glycomimetic in the gas phase and in solution: synthesis and conformation of the disaccharide Manalpha(1,6)-C-ManalphaOPh.

Journal article

The effect of carbon is subtle but sweet: The flexible C-linkage in the newly synthesised C-glycosyl mimetic, Manalpha(1,6)-C-ManalphaOPh allows OH--pi 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 Manalpha(1,6)-C-ManalphaOPh (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 Manalpha(1,6)-C-ManalphaOMe (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 (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 in an aqueous solution of 1 (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 1 was tested as a potential inhibitor, but displayed no significant inhibitory activity against Jack Bean alpha-mannosidase.

Authors: Drouin, L; Stanca-Kaposta, E; Saundh, P; Fairbanks, A; Kemper, S

• Publication status: Published
• Journal: Chemistry (Weinheim an der Bergstrasse, Germany)
• Volume: 15
• Issue: 16
• Pages: 4057-4069
• Publication date: 2009-01-01
• DOI: 10.1002/chem.200802179
• EISSN: 1521-3765
• ISSN: 0947-6539
• Language: English
• Keywords: Mannosides; Molecular Structure; alpha-Mannosidase; Magnetic Resonance Spectroscopy; Disaccharides