Synthesis and Conformational Behavior of the Difluoromethylene Linked C-glycoside Analog of Beta-galactopyranosyl-(1<-->1)-alpha-mannopyranoside

Overview

Journal Carbohydr Res

Publisher Elsevier

Specialties Biochemistry
Endocrinology

Date 2007 Jul 3

PMID 17601514

Citations 4

Authors

Richard W Denton

Kurissery A Tony

Jose Juan Hernandez-Gay

F Javier Canada

Jesus Jimenez-Barbero

David R Mootoo

Affiliations

Soon will be listed here.

Abstract

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.

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