The preferred conformation of 2-fluoro-2-deoxy β-D-mannopyranosyl fluoride. An X-ray crystallographic and 2-dimensional proton nuclear magnetic resonance study

Abstract

STEPHEN G. WITHERS, IAN P. STREET, and STEVEN J. RETTIG. Can. J. Chem. 64, 232 (1986). The preferred conformation of 2-fluoro-2-deoxy P-D-mann~pyran~Syl fluoride has been determined in the solid state by X-ray crystallography and in aqueous solution by 2-dimensional J-resolved proton nuclear magnetic resonance. Crystals of 2-fluoro-2-deoxy P-D-mannopyranosyl fluoride are monoclinic, a 4 10.9150(8), b 4 4.9079(4), c 4 6.9902(6) A, P = 105.158(4)", Z = 2, space group P2]. The structure was solved by direct methods and was refined by full-matrix least-squares procedures to R = 0.028 and R,, = 0.031 for 797 reflections with 1 2 3u(I). The sugar ring was present in an essentially undistorted 4CI chair conformation. Weak, but significant interactions, presumably hydrogen bonding of the type OH . .. 232 (1986). On a dCtermin6 la conformation privilCgiCe du fluorure du fluoro-2 dtoxy-2 P-D-mannopyrannosyle tant a 1'Ctat solide en faisant appel diffraction des rayons-X qu'en solution aqueuse en faisant appel a la rmn du 'H bidimensionnelle rCsolue pour J . Les cristaux du fluoru!e du fluoro-2 dCoxy-2 P-D-mannopyrannosyle sont monocliniques avec a= 10,9150(8), b=4,9079(4), c=6,9902(6) A, P = 105,158(4)", Z=2 et groupe d'espace P2'. On a rCsolu la structure par des methodes directes et on l'a affinCe par la mCthode des moindres carrCs (matrice entikre) jusqu'a des valeurs de R=0,028 et R, = 0,03 1 pour 797 rkflexions avec 1 2 3a(I). Le cycle du sucre existe essentiellement dans une conformation chaise 4~1 qui n'est pas dCformCe. Dans la maille du cristal, on observe des interactions faibles, mais significatives, qui sont probablement dues B des liaisons hydrogknes du type OH. . . F et CH . . . F. Les constantes de couplage observtes dans le spectre rmn du 'H en solution ne peuvent &tre expliqukes que par une conformation chaise 4~I .On discute brikvement de ces rksultats par rapport aux rCsultats obtenus rCcemment concernant l'interaction des sucres fluoro-dCoxy avec les sites de liaison enzymatique.[Traduit par le journal] IntroductionThe mode of interaction of carbohydrates and proteins has been attracting considerable interest of late, particularly since the antigenic determinants of red blood cells are oligosaccharides and it is their interaction with receptor proteins that is central to blood type recognition (1). In order to probe the intermolecular forces dominating such interactions, deoxy-and fluorodeoxy-saccharide analogues have been employed in several specificity studies (2-5). Such analogues are useful since the hydroxyl moiety is replaced by a smaller, and therefore sterically compatible, substituent, but one of different electronic properties. Systematic studies of mono-substituted derivatives can therefore provide information on the factors contributing to binding at each position. The enzyme glycogen phosphorylase provides a useful model system for a study of carbohydrate/ protein interactions since the three-dimensional structure of the glycogen phosphorylase/glucose complex has been determined by X-ray ...

Substrate Distortion by aβ-Mannanase: Snapshots of the Michaelis and Covalent-Intermediate Complexes Suggest aB2,5 Conformation for the Transition State

“…Pre‐incubation of the acid–base mutant Man26A E212A with 1 prior to crystallization allowed partial14 accumulation of a 2‐fluoromannotriosyl moiety covalently linked to the nucleophile E320. Intriguingly, the covalently linked −1 mannopyranoside ring was not observed in the expected 4 C 1 chair but instead adopts a conformation close to the O S 2 skew boat (Figure 1 c, Scheme ) 15. Together, the intermediate O S 2 and Michaelis 1 S 5 conformations flank the B 2,5 boat on the pseudorotational itinerary (Scheme ).…”

Glycosylidene Carbenes. Part 23. Regioselective glycosidation of deoxy‐ and fluorodeoxy‐myo‐inositol derivatives

“…considering that, as a rule, only strong intramolecular H-bonds are observed in the solid state [64], such as the H-bond between the two axial OH groups of 2 [19]. The F-substituent of (f)-4 is, however, involved in a weak F -H C interaction with H-C(3"') (F-H"' distance 2.360 A; for similar interactions, cc [26] [65]).…”

Protein-Carbohydrate Interactions

“…Chemically designed ligands have been used to assess the contribution made by individual hydrogen bonds (Withers et al, 1986;Bhattacharyya and Brewer, 1988;Quiocho, 1993). By using deoxy-and fluorodeoxy-saccharides, estimates for the strength of a hydrogen bond ranged from 0.5 to 3kcaJ mol"'.…”

“…The torsional freedom of the proton and lone pairs of a hydroxyl group on the carbohydrate 33 presumably allows optimisation of hydrogen bonds with the protein with some entropie cost due to fixing the rotamer. The ring oxygen of the sugar is sp^ hybridised, with the two bound carbons and the lone pairs of electrons of the ring oxygen arranged tetrahedrally allowing it to act as an acceptor of hydrogen bonds.Chemically designed ligands have been used to assess the contribution made by individual hydrogen bonds (Withers et al, 1986;Bhattacharyya and Brewer, 1988;Quiocho, 1993). By using deoxy-and fluorodeoxy-saccharides, estimates for the strength of a hydrogen bond ranged from 0.5 to 3kcaJ mol"'.…”