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.
). 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
, 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observed in aqueous solution (~64%) based on NMR studies (Zhang & Serianni, unpublished results).
Figure 1 The structure of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii. The minor component of the disorder has been removed for clarity.
An inspection of the Cremer–Pople puckering parameters (Cremer & Pople, 1975
) for (I)
and for the related aldohexopyranose, β-d
(Kouwijzer et al.
) (Table 1), shows that both structures are slightly distorted 4
chair forms (q3
). The degree of distortion varies slightly with structure, with θII
. The direction of distortion, embodied in the ϕ value, is different for (I)
, with a boat-like (B
) distortion observed in (I)
and a twist–boat (O5
) 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
-glucopyranose; θ = 4.80 (14)° and ϕ = 59.0 (16)°; Zhang et al.
) shows that C4 fluorination [θ = 7.16 (13)°] distorts the β-d
-glucopyranose ring [θ = 8.0 (3)°] slightly less than does C3 deoxygenation.
Table 1 Cremer–Pople puckering parameters for (I) and (II)
Figure 2 Ring distortions observed in compounds (I) and (II), based on Cremer–Pople parameters. B denotes the boat form and TB denotes the twist–boat form. The definition of ϕ is given in Cremer & Pople (1975 ).
The structural parameters for (I)
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)
Table 2 Comparison of structural parameters in (I) and (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)
Endocyclic torsion angles (absolute values) range from 50 to 66° in both (I)
, indicative of non-ideal chair conformations. Exocyclic hydroxymethyl conformations in (I)
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 O4
O2′ distance and O4—H4
O2′ 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)
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)
Figure 3 Packing diagrams of (a) (I) and (b) (II), viewed along the a axis. Dashed lines indicate hydrogen bonds.
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.