Synthesis and conformational behavior of the difluoromethylene linked C-glycoside analog of beta-galactopyranosyl-(1<-->1)-alpha-mannopyranoside.
C-Glycosides in which the pseudoglycosidic substituent is a methylene group have been advertised as hydrolytically stable mimetics of their parent O-glycosides. While this substitution assures greater stability, the lower polarity and increased conformational flexibility in the intersaccharide linker brought about by this change may compromise biological mimicry. In this regard, C-glycosides, in which the pseudoanomeric methylene is replaced with a difluoromethylene group, are interesting because the CF2 group is more of an isopolar replacement for oxygen than CH2. In addition, the CF2 residue is expected to instill conformational bias into the intersaccharide torsions. Herein is described the synthesis and conformational behavior of the difluoromethylene linked C-glycoside of beta-D-galactopyranosyl-(1<-->1)-alpha-D-mannopyranoside. The synthesis centers on the formation of the galactose residue via an oxocarbenium ion-enol ether cyclization. Conformational analysis, using a combination of molecular mechanics, dynamics, and NMR spectroscopy, suggests that the difluoro-C-glycoside populates the non-exo-Gal/exo-Man conformer to a major extent (ca 50%), with a minor contribution ( approximately 15%) from the exo-Gal/exo-Man conformer that corresponds to the ground sate of the parent O-glycoside.
Denton
Richard W
RW
Department of Chemistry, Hunter College, 695 Park Avenue, New York, NY 10021, USA.
Tony
Kurissery A
KA
Hernández-Gay
José Juan
JJ
Cañada
F Javier
FJ
Jiménez-Barbero
Jesús
J
Mootoo
David R
DR
D002236:Carbohydrate Conformation; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D005697:Galactosides / Q000737:chemistry*; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D007202:Indicators and Reagents; D008358:Mannose / Q000737:chemistry*; D008958:Models, Molecular
D004187:Disaccharides; D005697:Galactosides; D006027:Glycosides; D006845:Hydrocarbons, Fluorinated; D007202:Indicators and Reagents; C007816:beta-galactoside; C102075:difluoromethane; D008358:Mannose