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 1 adopts a (4)C(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 (4)C(1) chair conformation. Surprisingly, compound 2 exhibits a different equilibrium between (1)C(4) chair and (1)S(3) skew boat conformations and significant flexibility around the pseudoglycosidic linkage when in solution. The beta-stereoisomer 3 adopts a major (4)C(1) 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.
Kolympadi
Maria
M
Laboratoire de Glycochimie et Synthèse Asymétrique, Swiss Federal Institute of Technology (EPFL), Batochime, 1015 Lausanne, Switzerland.
Fontanella
Marco
M
Venturi
Chiara
C
André
Sabine
S
Gabius
Hans-Joachim
HJ
Jiménez-Barbero
Jesús
J
Vogel
Pierre
P
D002236:Carbohydrate Conformation; D005697:Galactosides / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010940:Plant Proteins / Q000737:chemistry; D054790:Ribosome Inactivating Proteins, Type 2 / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000737:chemistry*
D005697:Galactosides; D006845:Hydrocarbons, Fluorinated; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C488862:mistletoe lectin I; C102075:difluoromethane