Diosgenin hemihydrate

Diosgenin [or (22R,25R)-spirost-5-en-3β-ol] is the starting material of the Marker degradation, a cheap semi-synthesis of progesterone, which has been designated as an International Historic Chemical Landmark. Thus far, a single X-ray structure for diosgenin is known, namely its dimethyl sulfoxide solvate [Zhang et al. (2005 ▶). Acta Cryst. E61, o2324–o2325]. We have now determined the structure of the hemihydrate, C27H42O3·0.5H2O. The asymmetric unit contains two diosgenin molecules, with quite similar conformations, and one water molecule. Hydroxy groups in steroids and water molecules form O—H⋯O hydrogen-bonded R 5 4(10) ring motifs. Fused edge-sharing R(10) rings form a backbone oriented along [100], which aggregates the diosgenin molecules in the crystal structure.

Diosgenin [or (22R,25R)-spirost-5-en-3-ol] is the starting material of the Marker degradation, a cheap semi-synthesis of progesterone, which has been designated as an International Historic Chemical Landmark. Thus far, a single X-ray structure for diosgenin is known, namely its dimethyl sulfoxide solvate [Zhang et al. (2005). Acta Cryst. E61, o2324-o2325]. We have now determined the structure of the hemihydrate, C 27 H 42 O 3 Á0.5H 2 O. The asymmetric unit contains two diosgenin molecules, with quite similar conformations, and one water molecule. Hydroxy groups in steroids and water molecules form O-HÁ Á ÁO hydrogen-bonded R 5 4 (10) ring motifs. Fused edge-sharing R(10) rings form a backbone oriented along [100], which aggregates the diosgenin molecules in the crystal structure.

International Historic Chemical Landmark by the American Chemical Society and the Sociedad Química de México.
However, the X-ray structure of diosgenin remains unknown, and only the dimethyl sulfoxide solvate has been characterized crystallographically so far (Zhang et al., 2005). This is not surprising, taking into account the poor solubility of this steroid in polar solvents (Chen et al., 2012).
We have now crystallized diosgenin hemihydrate. The asymmetric unit contains two diosgenin molecules and one lattice water molecule (Fig. 1). Diosgenin displays a rigid conformation, as reflected by the small r.m.s. deviation for the fit between independent molecules, of 0.16 Å. This conformation is also very close to that observed in the DMSO solvate (Zhang et al., 2005; with r.m.s. deviations with the molecules of the title crystal: 0.22 and 0.23 Å).
In contrast with the DMSO solvate, in which discrete hydrogen bonds are formed between the steroid and the solvent, the hemihydrate gives rise to a supramolecular structure. Ring motifs R 5 4 (10) are formed by three diosgenin and two water molecules. These motifs share edges with neighboring symmetry-related R(10) rings, forming a chain of fused rings in the crystal (Fig. 2), oriented in the [100] direction. This backbone based on efficient hydrogen bonds aggregates molecules in the crystal, and allows the crystallization of the hemihydrate. Such one-dimensional supramolecular structure is found in other steroids hydrates. Indeed, 11 identical supramolecular arrangements were found in the CSD, predominantly for androstane and androstene derivatives hydrates (e.g. Xia et al., 2005). It thus seems that these kind of steroids functionalized with an alcohol group at C3 should have a propensity to crystallize as hydrates, since a stabilizing supramolecular structure may be arranged.

Experimental
Diosgenin hemihydrate was initially obtained as unreacted material in a reaction attempt between diosgenin and terephthaloyl chloride. The same hemihydrate may be obtained by stirring diosgenin in CH 2 Cl 2 (1 mmol in 20 ml) until complete dissolution. After washing the solution with distilled water, the organic phase is dried with anhydrous Na 2 SO 4 , filtered, and concentrated under reduced pressure. The residue is then crystallized from hexane/acetone (3:2).

Refinement
The search for a single-crystal was challenging. After a number of attempts, a sample with a thickness limited to 0.03 mm was collected, although data reduction revealed that it was not a single-crystal. The poor sample quality is reflected in the supplementary materials sup-2 . E68, o2357 high residual for symmetry-equivalent reflections, R int = 0.131. Hydroxy H atoms, H3, H53, H1W and H2W, were found in a difference map and refined freely. The geometry for the water molecule was however restrained, with O-H = 0.85 (2) Å, and H1W···H2W = 1.34 (1) Å. Other H atoms, bonded to C atoms, were placed in idealized positions and refined as riding to their carrier atoms. Isotropic displacement parameters for H atoms were calculated as U iso (H) = xU eq (carrier atom) where x = 1.5 for methyl H atoms and x = 1.2 for other H atoms. The absolute configuration was assigned from chiral centers with known configuration in the steroidal nucleus, and measured Friedel pairs (3683) were merged.

Figure 1
The asymmetric unit of the title compound. Displacement ellipsoids for non-H atoms are drawn at the 50% probability level.

Figure 2
A part of the one-dimensional supramolecular structure of the title compound, based on six diosgenin and three water molecules. H atoms not involved in hydrogen bonds have been omitted, and the projection is normal to [010]. One R (10) motif is shown as a solid yellow polygon, with H-bonds components of the edges displayed as dashed bonds.