Synthesis and Conformational Analysis of (alpha-D-Galactosyl)phenylmethane and alpha-,beta-Difluoromethane Analogues: Interactions with the Plant Lectin Viscumin
alpha-D-Galactosyl)phenylmethane (1). (alpha- and beta-D-galactosyl)-(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 I adopts a C-4(1) chair conformation and an exo anomeric orientation. as is the case for natural alpha-galactosides. The X-ray crystal structure of its difluoromethylene derivative 2 similarly shows a C-4(1) chair conformation. Surprisingly, compound 2 exhibits a different equilibrium between C-1(4) chair and S-1(3) skew boat conformations and significant flexibility around the pseudoglycosidic linkage when in solution. The beta-stereoisomer 3 adopts a major C-4(1) chair conformation. Interestingly, C-galactosides 1, 2, and 3 bind to viscurnin (VAA), a galactoside-specific lectin, which is confirmed by NMR experiments and docking calculations.