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4-Deoxy-4-fluoro-β-d-glucopyranose, C6H11FO5, (I), crystallizes from water at room temperature in a slightly distorted 4 C 1 chair conformation. The observed chair distortion differs from that observed in β-d-glucopyranose [Kouwijzer, van Eijck, Kooijman & Kroon (1995 ). Acta Cryst. B51, 209–220], (II), with the former skewed toward a B C3,O5 (boat) conformer and the latter toward an O5 TB C2 (twist–boat) conformer, based on Cremer–Pople analysis. The exocyclic hydroxymethyl group conformations in (I) and (II) are similar; in both cases, the O—C—C—O torsion angle is ~−60° (gg conformer). Intermolecular hydrogen bonding in the crystal structures of (I) and (II) is conserved in that identical patterns of donors and acceptors are observed for the exocyclic substituents and the ring O atom of each monosaccharide. Inspection of the crystal packing structures of (I) and (II) reveals an essentially identical packing configuration.
Fluorosugars find diverse applications in saccharide chemistry and biochemistry (Taylor, 1988 ), ranging from their use as activated donors in chemical glycosylations (e.g., glycosyl fluorides) (Yokoyama, 2000 ) to their use as molecular probes of enzyme reaction mechanisms (e.g., a covalent mechanism for lysozyme) (White et al., 1996 ). In this laboratory, specific fluorosugars have been prepared recently to investigate the mechanisms of protein-bound saccharide rearrangements that accompany non-enzyme-catalyzed protein glycation. One of these fluorosugars, 4-deoxy-4-fluoro-β-d-glucose, (I), crystallizes from water in the β-pyranose form (Fig. 1 ), which is the predominant tautomer of (I) observed in aqueous solution (~64%) based on NMR studies (Zhang & Serianni, unpublished results).
An inspection of the Cremer–Pople puckering parameters (Cremer & Pople, 1975 ) for (I) and for the related aldohexopyranose, β-d-glucopyranose, (II) (Kouwijzer et al., 1995 ) (Table 1 ), shows that both structures are slightly distorted 4 C 1 chair forms (q3 >> q2). The degree of distortion varies slightly with structure, with θII > θI. The direction of distortion, embodied in the ϕ value, is different for (I) and (II), with a boat-like (B C3,O5) distortion observed in (I) and a twist–boat (O5 TB C2) distortion observed in (II) (Fig. 2 ), based on idealized ϕ values of 0° for (I) and 330° for (II). Comparison with the crystal structure of 3-deoxy-β-d-ribo-hexopyranose (3-deoxy-β-d-glucopyranose; θ = 4.80 (14)° and ϕ = 59.0 (16)°; Zhang et al., 2007 ) shows that C4 fluorination [θ = 7.16 (13)°] distorts the β-d-glucopyranose ring [θ = 8.0 (3)°] slightly less than does C3 deoxygenation.
The structural parameters for (I) and (II) are compared in Table 2 . The endocyclic C—C bond lengths vary by ~0.01 Å between the two structures, with the C1—C2, C2—C3 and C4—C5 bonds elongated and the C3—C4 bond shortened in the fluorosugar. The exocyclic C5—C6 bond is essentially unchanged in the two structures. The endocyclic C1—O5 bond is ~0.01 Å longer in (I), whereas the C5—O5 bond is ~0.01 Å shorter. It is noteworthy that the largest difference in exocyclic C—O bond lengths occurs for C1—O1, which is nearly 0.03 Å shorter in the fluorosugar, (I). This latter effect is notable, considering that the site of F substitution is maximally displaced from the C1—O1 bond in terms of numbers of intervening covalent bonds. As expected, the exocyclic C4—F bond in (I) is about 0.02 Å shorter than the corresponding C4—O4 bond in (II).
Of the three endocyclic C—C—C bond angles, the C3—C4—C5 angle shows the greatest change, increasing by 2.5° in the fluorosugar. In contrast, the exocyclic C4—C5—C6 angle is 1.9° smaller in the fluorosugar. The C4—C5—O5 and C5—O5—C1 angles are essentially the same in (I) and (II).
Endocyclic torsion angles (absolute values) range from 50 to 66° in both (I) and (II), indicative of non-ideal chair conformations. Exocyclic hydroxymethyl conformations in (I) and (II) are gg (H5 anti to O6), with virtually identical O5—C5—C6—O6 torsion angles [−59.56 (16) and −60.4 (3)°].
All of the hydroxy H atoms in (I) serve as intermolecular hydrogen-bond donors, and atoms O2, O3, O5 and O6 serve as mono-acceptors in intermolecular hydrogen bonds, which link the molecules into a three-dimensional network. Atoms O1 and F do not act as hydrogen-bond acceptors within the hydrogen-bonding scheme. In comparison, all of the hydroxy H atoms in (II) serve as hydrogen-bond donors [the O4O2′ distance and O4—H4O2′ angle are 3.122 (3) Å and 140 (4)°, respectively] and atoms O1 and O4 do not act as hydrogen-bond acceptors. Remarkably, the overall packing motifs of (I) and (II) are essentially identical (Fig. 3 ) and the primary differences are minor changes in the cell parameters, notably a slight contraction of the b axis [9.2055 (3) cf 9.014 (2) Å] and an expansion of the c axis [12.6007 (3) cf 12.720 (2) Å] on going from (I) to (II).
The hydroxy atom O1 was found to be disordered over two positions, with the second very minor position with occupancy 0.06 (1) corresponding with the α-anomer. NMR spectra indicate that (I) is chemically pure. However, saccharides are known to undergo spontaneous anomerization in aqueous solution and it is plausible that this occurred during crystallization, resulting in the minor component observed.
Synthesis details for the preparation of 4-deoxy-4-fluoro-d-[2-13C]glucopyranose are given in the Supplementary material. After isolation and purification, this 13C isotopomer of (I) was dissolved in a minimal volume of distilled water and the solution was left at room temperature. Crystals of the title β-pyranose, (I), formed slowly and were harvested for structure determination.
Hydroxy atom O1 was found to be partially disordered with a very minor α-anomer component. The model was refined with the site occupancies of atoms O1 and O1A constrained to sum to unity, yielding values of 0.94 (1) and 0.06 (1), respectively. Due to the weak electron density at the minor component site, the C—O bond distances were restrained to be the same within experimental error and atom O1A was refined isotropically. The minor-component bond distances and angles are reported in the archived CIF. H atoms were positioned geometrically and treated as riding, with C—H = 0.99–1.00 Å and O—H = 0.84 Å, and with U iso(H) = 1.2U eq(C,O). The absolute stereochemistry was determined by the known configuration of the initial compound (methyl α-d-[2-13C]galactopyranoside). The stereochemistry was retained throughout the synthesis and the structure of the title compound is in agreement with this assessment. A measurement of the Hooft y parameter (Hooft et al., 2008 ) gives a value of 0.09 (5), and P2(true) and P3(true) values of 1.000 and 1.000, respectively.
Data collection: APEX2 (Bruker–Nonius, 2008 ); cell refinement: SAINT (Bruker–Nonius, 2008 ); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: XP (Sheldrick, 2008 ), POV-Ray (Cason, 2003 ) and DIAMOND (Brandenburg, 2009 ); software used to prepare material for publication: XCIF (Sheldrick, 2008 ), enCIFer (Allen et al., 2004 ), publCIF (Westrip, 2010 ) and PLATON (Spek, 2009 ).
Crystal structure: contains datablocks I, global. DOI: 10.1107/S0108270110034001/fn3060sup1.cif
This work was supported by the National Institute of Diabetes and Digestive and Kidney Disease (research grant No. DK065138).
Supplementary data for this paper are available from the IUCr electronic archives (Reference: FN3060). Services for accessing these data are described at the back of the journal.