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A C ‐linked Glycomimetic in the Gas Phase and in Solution: Synthesis and Conformation of the Disaccharide Manα(1,6)‐ C ‐ManαOPh
Author(s) -
Drouin Ludovic,
StancaKaposta E. Cristina,
Saundh Priptal,
Fairbanks Antony J.,
Kemper Sebastian,
Claridge Timothy D. W.,
Simons John P.
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200802179
Subject(s) - conformational isomerism , disaccharide , chemistry , glycosidic bond , dihedral angle , hydrogen bond , crystallography , aqueous solution , alkane stereochemistry , infrared spectroscopy , stereochemistry , computational chemistry , crystal structure , organic chemistry , molecule , enzyme
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.