Synthesis and Conformational Analysis of (a-d-Galactosyl)henylmethane and a-,b-Difluoromethane Analogues: Interactions with the Plant Lectin Viscumin

摘要

(a-d-Galactosyl)phenylmethane (1), (a- and b-d-galactosyl)-ACHTUNGTRENUNG(difluoro)phenylmethane (2 and 3)have been prepared and their conformations in solution were described by using a combination of force-field calculations and NMR spectroscopic studies.Galactoside 1 adopts a 4C1 chair conformation and an exo anomeric orientation,as is the case for natural agalactosides.The X-ray crystal structure of its difluoromethylene derivative 2 similarly shows a 4C1 chair onformation. Surprisingly, compound 2 exhibits a different equilibrium between 1C4 chair and 1S3 skew boat conformations and significant flexibility around the pseudoglycosidic linkage when in solution.The b-stereoisomer 3 adopts a major 4C1 chair conformation. Interestingly,C-galactosides 1, 2, and 3 bind to viscumin (VAA), a galactoside-specific lectin, which is confirmed by NMR experiments and docking calculations.