A C-linked glycomimetic in the gas phase and in solution: synthesis and conformation of the disaccharide Manalpha(1,6)-C-ManalphaOPh.
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.
Drouin
Ludovic
L
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, UK.
Stanca-Kaposta
E Cristina
EC
Saundh
Priptal
P
Fairbanks
Antony J
AJ
Kemper
Sebastian
S
Claridge
Timothy D W
TD
Simons
John P
JP
D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008362:Mannosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D043323:alpha-Mannosidase / Q000187:drug effects*
D004187:Disaccharides; D008362:Mannosides; C540308:manalpha(1,6)-C-manalphaOPh C-disaccharide; D043323:alpha-Mannosidase