(25R)-6α-Hydroxy-5α-spirostan-3β-yl tosylate

The title steroid, C34H50O6S, is an intermediate on the synthetic route between diosgenin and brassinosteroids, which possess the A ring modified with the 2α,3α-diol functionality. The polycyclic spirostan system has the expected conformation, with six-membered rings adopting chair forms and the five-membered rings envelope forms (flap atoms are the methine C atom in the C/D-ring junction and the spiro C atom connecting rings E and F). The 3β-tosylate group is oriented in such a way that S=O bonds are engaged in intermolecular hydrogen bonds with O—H and C—H donors. Chains of molecules are formed along [100] via O—H⋯O hydrogen bonds, and secondary weak C—H⋯O interactions connect two neighbouring chains in the [001] direction.

The title steroid, C 34 H 50 O 6 S, is an intermediate on the synthetic route between diosgenin and brassinosteroids, which possess the A ring modified with the 2,3-diol functionality. The polycyclic spirostan system has the expected conformation, with six-membered rings adopting chair forms and the five-membered rings envelope forms (flap atoms are the methine C atom in the C/D-ring junction and the spiro C atom connecting rings E and F). The 3-tosylate group is oriented in such a way that S O bonds are engaged in intermolecular hydrogen bonds with O-H and C-H donors. Chains of molecules are formed along [100] via O-HÁ Á ÁO hydrogen bonds, and secondary weak C-HÁ Á ÁO interactions connect two neighbouring chains in the [001] direction.
Commonly, the crude product after the hydroboration-oxidation procedure is immediately oxidized in order to obtain the 6-keto derivative; we decided instead, to isolate and properly characterize the 6-hydroxy intermediate.
The compound crystallizes with one molecule in the asymmetric unit ( Fig. 1) and the conformation of the A-F ring system is as expected for a spirostan nucleus. All 6-membered rings have a chair conformation, while 5-membered rings D and E are envelopes on C14 and C22, respectively. The tosylate group in equatorial position at C3 is oriented in such a way that a potential intramolecular stabilizing O-H···π contact could be formed between the hydroxyl group at C6 and the benzene ring of the tosylate. However, this interaction should have an energy approaching zero, because of the too long H···π separation, ca. 4.4 Å. On the other hand, the tosylate orientation in the title compound is similar to that observed in cholesteryl tosylate (Cox et al., 1996), which has C-6 engaged in a double bond. This suggests that the tosylate orientation results from packing restraints or intermolecular interactions rather than intramolecular contacts.
Regarding the crystal structure, the single feature of interest is the intermolecular hydrogen bond formed between the hydroxyl group and one S═O group in the tosylate. These contacts link molecules in chains oriented in the [100] direction in the crystal. A weak hydrogen bond involving the other S═O group is observed between chains, C40-H40A···O34, characterized by a small C-H···O angle of 133° (Fig. 2).

Experimental
Diosgenin (750 mg, 1.8 mmol) was tosylated by means of p-TsCl/py/DCM, following the standard procedure, affording diosgenin tosylate quantitatively; the crude was properly washed, dried and immediately submitted to the next reaction.
Diosgenin tosylate (1 g, 1.76 mmol) was dissolved in THF (30 ml) and NaBH 4 (0.4 g, 10.8 mmol) was added. The system was sealed under Ar atmosphere and then, BF 3 . Et 2 O (0.7 ml, 5.6 mmol) was carefully added. The reaction mixture was kept for 2 h at room temperature, concentrated under reduced pressure, and re-dissolved in a solution of KOH/MeOH (2%, 50 ml), followed by 5 ml of 35% H 2 O 2 . The reaction mixture was stirred for 1 h; then the addition of water produced a precipitate, which was filtered off, washed with cold water, and dried under high vacuum. The resulting white powder was purified by column chromatography with hexanes/EtOAc 7:3 to afford the title compound as a white powder.

Refinement
Hydroxyl H atom H30 was found in a difference map and refined with free coordinates and isotropic U parameter. Other H atoms were placed in idealized positions and refined with a riding model and fixed isotropic U parameters. C-H bond lengths were fixed to 0.96 (methyl), 0.97 (methylene), or 0.98 Å (methine). Displacement parameters were calculated as U iso (H) = xU eq (parent C) where x = 1.5 (methyl) or 1.2 (methylene, methine). Anomalous dispersion of the tosylate S atom allowed to refine a Flack parameter (Flack, 1983), which is in agreement with the expected absolute configuration for the molecule.