3β,5α,6β-Trihydroxyandrostan-17-one

The title compound, C19H30O4, is an androstan-17-one derivative synthesized from the dehydroepiandrosterone through a sequential addition of an oxidant, followed by a trans-diaxial opening of the epoxide generated, with Bi(OTf)3 (OTf is trifluoromethanesulfonate). The six-membered rings have a slightly flattened chair conformation, while the five-membered ring adopts a 14-α envelope conformation. All rings are trans fused. In the crystal, the molecules are connected by O—H⋯O hydrogen bonds involving the hydroxyl and carbonyl groups, forming a three-dimensional network. A quantum mechanical ab initio Roothan Hartree–Fock calculation of the free molecule gives bond lengths, valency angles and ring torsion angles of the free molecule at equilibrium geometry (energy minimum) close to the experimental values.

The title compound, C 19 H 30 O 4 , is an androstan-17-one derivative synthesized from the dehydroepiandrosterone through a sequential addition of an oxidant, followed by a trans-diaxial opening of the epoxide generated, with Bi(OTf) 3 (OTf is trifluoromethanesulfonate). The six-membered rings have a slightly flattened chair conformation, while the fivemembered ring adopts a 14-envelope conformation. All rings are trans fused. In the crystal, the molecules are connected by O-HÁ Á ÁO hydrogen bonds involving the hydroxyl and carbonyl groups, forming a three-dimensional network. A quantum mechanical ab initio Roothan Hartree-Fock calculation of the free molecule gives bond lengths, valency angles and ring torsion angles of the free molecule at equilibrium geometry (energy minimum) close to the experimental values.
supplementary materials sup-2 In order to gain some insight on how the crystal packing of (I) might affect the molecular geometry we have performed quantum chemical calculations on the equilibrium geometry of the free molecule. The calculations were performed with the computer program GAMESS (Schmidt et al., 1993).
The ab-initio calculations reproduce well the observed experimental bond lengths and valency angles of the molecule.
Also, the calculated conformation of the rings are very close to the experimental values.
The molecules are hydrogen-bonded via the hydroxyl and carbonyl groups forming a three-dimension hydrogen bond pattern. Each hydroxyl group acts as both donnor and acceptor, thus full potential for hydrogen bonding is achieved in the crystal struture. In addition to these bonds, three weak intramolecular interactions can be spotted involving atoms O5 and O6 and CH, CH 2 and CH 3 groups.

Experimental
Synthesis of (I) was performed using a new and recently reported (Carvalho et al., 2010b) fast and high yielding sequential chemical approach for the straightforward preparation of 5α,6β-dihydroxy-steroids using 3β-hydroxy-Δ 5 -steroids as raw materials. The protocol involves two steps: (i) formation of the epoxide from Δ 5 -steroids, using MMPP as oxidative agent; and (ii) trans-diaxial epoxide opening with Bi(OTf) 3 in commercial acetone. Crystallization from ethanol at room temperature afforded colorless crystals suitable for X-ray analysis. Analytical data of compound (I) is in accordance with the literature (Carvalho et al., 2010b).

Refinement
All hydrogen atoms were refined as riding on their parent atoms using SHELXL97 defaults. The absolute configuration was not determined from the X-ray data, as the molecule lacks any strong anomalous scatterer atom at the Mo Kα wavelength, but was known from the synthetic route. Friedel pairs were merged before refinement. Fig. 1  Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.