Received 31 August 2011
Comparison of racemic epi-inosose and (-)-epi-inosose
The conversion of myo-inositol to epi-inositol can be achieved by the hydride reduction of an intermediate epi-inosose derived from myo-inositol. (-)-epi-Inosose, (I), crystallized in the monoclinic space group P21, with two independent molecules in the asymmetric unit [Hosomi et al. (2000). Acta Cryst. C56, e584-e585]. On the other hand, (2RS,3SR,5SR,6SR)-epi-inosose, C6H10O6, (II), crystallized in the orthorhombic space group Pca21. Interestingly, the conformation of the molecules in the two structures is nearly the same, the only difference being the orientation of the C-3 and C-4 hydroxy H atoms. As a result, the molecular organization achieved mainly through strong O-HO hydrogen bonding in the racemic and homochiral lattices is similar. The compound also follows Wallach's rule, in that the racemic crystals are denser than the optically active form.
epi-Inositol is known to affect regulation of the myo-inositol biosynthetic pathway (Shaldubina et al., 2002) and has been evaluated as a potential antidepressant drug that could interact with the Li+ ion and myo-inositol receptors in the brain (Einat et al., 1998; Belmaker et al., 1998; Williams et al., 2002). We have reported previously the synthesis of epi-inositol by the reduction of racemic epi-inosose (Patil et al., 2011).
A Cambridge Structural Database (CSD, Version 5.31; Allen, 2002) search yielded the structure of the optically active (-)-epi-inosose (CSD refcode XEGVUA; Hosomi et al., 2000) prepared enantioselectively by a bioconversion from myo-inositol (Hosomi et al., 2000). We were thus presented with an opportunity for the comparison of the molecular assembly in the crystals of these homochiral, (I), and racemic, (II), inososes. Single-crystal X-ray intensity measurements for crystals of (II) were recorded at ambient temperature (297 K), as reported for (I). Crystals of the racemic ketone are orthorhombic, belonging to the noncentrosymmetric space group Pca21 (Fig. 1), while the homochiral ketone crystallizes in the noncentrosymmetric space group P21, with two independent molecules (A and B) in the asymmetric unit. The atom numbering for the racemic form is consistent with that reported for the optically active compound to enable easier comparison of the crystal structures.
The superimposition of the molecules in the asymmetric unit of (I) and the corresponding enantiomer in (II) reveals an excellent fit of the non-H atoms, with r.m.s. deviations of 0.0058 and 0.0094 Å for the overlaid non-H atoms shown in Figs. 2a and 2b, respectively. The most significant differences are in the orientations of the hydroxy H atoms at C3 and C4. The conformation of the C3 hydroxy H atom of (II) matches that of molecule B in the asymmetric unit of crystals of (I), whereas the conformation of the C4 hydroxy group matches that of molecule A.
There is a close correspondence in the unit-cell parameters of the two structures: the a axes lengths are nearly the same and interchange of the b and c axes of the orthorhombic racemic form results in edge lengths that are nearly identical to those of the homochiral crystal lattice [a = 11.197 (2), b = 8.932 (2), c = 6.976 (2) Å and = 90.21 (2)° for (I)]. In accordance with Wallach's rule (Wallach, 1895; Brock et al., 1991), the racemic crystal is 1.7% denser than the enantiomerically pure crystal, and its melting point is 492-495 K. The melting point of the crystals of (I) is not available for comparison. The unit cell of racemic epi-inosose consists of four molecules, i.e. two pairs of enantiomers, whereas that of (-)-epi-inosose contains two pairs of the two symmetry-independent molecules of the asymmetric unit.
The presence of five hydroxy groups and a carbonyl group results in extensive hydrogen-bonding interactions in the crystal. In the crystals of (II), each enantiomer forms a homochiral hydrogen-bonded chain along the c axis through O6-H6O4v, with adjacent heterochiral molecular chains along the a axis linked by short and linear O3-H3O2ii, O4-H4O6iii, O5-H5O3iv and C3-H8O4vii interactions (Fig. 3a, symmetry codes and geometric parameters in Table 1). In the case of (I), each of the two molecules in the asymmetric unit forms a similar O6-H5O4viii hydrogen-bonded chain along the b axis. Interestingly, the carbonyl O atom (O7) of only one of the molecules of (I) (molecule B) is involved in O-HO hydrogen bonding [O9-H12O7xi; symmetry codes for (I) as in Fig. 3b], because of the conformational differences in the hydroxy groups of the two molecules in the asymmetric unit. The adjacent molecular chains along the a axis are linked by a large number of hydrogen-bonding interactions (Fig. 3b).
A view of these molecular chains down the c axis in (II) and b axis in (I) shows a corrugated-sheet-like assembly (Fig. 4). Adjacent sheets are linked by bifurcated hydrogen-bonding interactions involving carbonyl atom O1 (O2-H2O1i and C2-H7O1vi) and O2-H2O6i and C6-H11O2vi contacts in the racemic crystal (Fig. 4a and Table 1). In the crystals of the optically active form, neighbouring sheets are linked by O2-H1O9xv, O3-H2O10xv, O10-H13O11xvi, O11-H14O6xiv, C2-H6O1xiii and C6-H10O2xiii contacts (Fig. 4b). Thus, the overall molecular organization in the crystals of the racemic and enantiopure compound is remarkably similar. This is primarily due to the fact that the second molecule in the asymmetric unit of (I) plays the role of the second enantiomer in the crystal packing. While the thermodynamic stability of the two crystals cannot be experimentally evaluated owing to the absence of adequate thermal data, estimation of lattice energies for (I) and (II) using the Oprop module of the OPiX program suite (Gavezzotti, 2003) yielded a value of -204.75 kJ mol-1 for (I) and -253.5 kJ mol-1 for (II), consistent with the crystal densities.
| || Figure 1 |
The molecular structure of racemic epi-inosose, (II) [the (2R,3S,5S,6S)-enantiomer], showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
| || Figure 2 |
The overlap of the molecules in the crystals of (-)-epi-inosose, (I), and racemic epi-inosose, (II), showing the differences in the orientations of the hydroxy groups. In (a), one of the two independent molecules in the asymmetric unit of (I) (blue in the electronic version of the paper) and the corresponding enantiomer in (II) (red) is shown, while in (b) the second independent molecule in the asymmetric unit of (I) (green) and the corresponding enantiomer in (II) (red) is shown.
| || Figure 3 |
Chains of molecules linked through hydrogen-bonding interactions (dotted lines) in the crystal structures of (a) (II) and (b) (I). The different colours represent the enantiomers of (II) in (a) (dark blue and light blue in the electronic version of the paper) and the independent molecules in the asymmetric unit of (I) in (b) (purple and light pink). H atoms not involved in hydrogen bonding have been omitted. [Symmetry codes: (ii) -x + , y, z + ; (iii) x + , -y, z; (iv) x - , -y, z; (v) -x, -y, z - ; (vii) -x + , y, z - ; (viii) -x + 2, y - , -z; (ix) -x + 2, y + , -z; (x) -x + 1, y + , -z; (xi) -x + 1, y - , -z; (xii) x, y - 1, z.]
| || Figure 4 |
A view of the molecular packing down (a) the c axis in crystals of (II) and (b) the b axis in crystals of (I). Dotted lines represent hydrogen-bonding interactions, some of which (shown in Fig. 3) have been omitted for clarity. [Symmetry codes: (i) x + , -y + 1, z; (vi) -x, -y + 1, z + ; (xiii) x + 2, y + , -z + 1; (xiv) -x + 2, y - , -z + 1; (xv) -x + 1, y + , -z + 1; (xvi) -x + 1, y - , -z + 1.]
All inositol ring H atoms were placed in geometrically idealized positions, with C-H = 0.98 Å. They were constrained to ride on their parent atoms, with Uiso(H) = 1.2Ueq(C). The O-bound H atoms were located in difference Fourier maps and refined isotropically. The refined O-H distances were in the range 0.79 (3)-0.91 (3) Å. Although (I) is racemic, it crystallizes in a noncentrosymmetric space group. In the absence of strong anomalously scattering elements in the structure, the absolute structure was chosen arbitrarily and the Friedel pairs were merged prior to structure refinement.
Data collection: SMART (Bruker, 2003); cell refinement: SAINT (Bruker, 2003); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).
Supplementary data for this paper are available from the IUCr electronic archives (Reference: SF3158 ). Services for accessing these data are described at the back of the journal.
SK and MTP are recipients of Senior Research Fellowships from CSIR, New Delhi, India. This work was supported by the Department of Science and Technology, New Delhi, India.
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