3β-Acet­oxy-19-hy­droxy-Δ5-pregnen-20-one

Aike Meier zu Greffen; Darius P Kranz; Jörg-M Neudörfl; Hans-Günther Schmalz

doi:10.1107/S1600536813002493

. 2013 Jan 31;69(Pt 2):o313. doi: 10.1107/S1600536813002493

3β-Acetoxy-19-hydroxy-Δ⁵-pregnen-20-one

Aike Meier zu Greffen ^a, Darius P Kranz ^a, Jörg-M Neudörfl ^a, Hans-Günther Schmalz ^a,^*

PMCID: PMC3569832 PMID: 23424578

Abstract

In the title compound, C₂₃H₃₄O₄, the C/D and D/E rings are trans fused and the A/B ring possesses an anti fusion. The two cyclohexane rings adopt a chair conformation while the cyclohexene ring exhibits a half-chair conformation. The cyclopentane ring displays an envelope conformation with the C atom bearing the methyl group as the flap. In the crystal, the molecules are linked by O—H⋯O hydrogen bonds, forming chains along the b axis.

Related literature

For an overview of steroids as biologically important molecules, see: Fieser & Fieser (1961) ▶; Hanson (2010 ▶). For examples of steroids possessing a rearranged A/B-ring system, see: Du et al. (2008 ▶); Aoki et al. (2006 ▶); Flyer et al. (2010 ▶). For related C-19-functionalized steroids, see: El Sheikh et al. (2007 ▶); Shenvi et al. (2008 ▶). For an overview of remote functionalization, see: Reese (2001 ▶); Heusler & Kalvoda (1964 ▶). For the first synthesis of the title compound, see: Halpern et al. (1963 ▶). For examples of the title compound as an intermediate for rearranged A/B-ring systems, see: Knox et al. (1965 ▶); Kranz et al. (2011 ▶). For a description of the Cambridge Structural Database, see: Allen (2002 ▶).

Experimental

Crystal data

C₂₃H₃₄O₄
M _r = 374.50
Orthorhombic,
a = 8.6960 (6) Å
b = 12.3708 (4) Å
c = 18.3303 (10) Å
V = 1971.91 (18) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 100 K
0.3 × 0.3 × 0.3 mm

Data collection

Nonius KappaCCD diffractometer
9889 measured reflections
2457 independent reflections
1943 reflections with I > 2σ(I)
R _int = 0.044

Refinement

R[F ² > 2σ(F ²)] = 0.037
wR(F ²) = 0.079
S = 0.99
2457 reflections
247 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: COLLECT (Hooft 1998 ▶); cell refinement: DENZO (Otwinowski & Minor, 1997 ▶); data reduction: DENZO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SCHAKAL99 (Keller, 1999 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Click here for additional data file.^{(30.4KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813002493/lr2076sup1.cif

e-69-0o313-sup1.cif^{(30.4KB, cif)}

Click here for additional data file.^{(120.7KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813002493/lr2076Isup2.hkl

e-69-0o313-Isup2.hkl^{(120.7KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3A⋯O2ⁱ	0.84	2.19	2.9305 (19)	147

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Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

The structural diversity of steroids as well as their unsurpassed biological potential qualify them as challenging targets for chemical synthesis and as lead structures for pharmacological research (Fieser & Fieser, 1961; Hanson, 2010). In recent years, some unusual steroids displaying a rearranged A/B-ring system with promising biological properties have been reported (Du et al., 2008; Aoki et al., 2006; Flyer et al., 2010). Important intermediates for the synthesis of such rearranged derivatives are C-19 functionalized steroids (El Sheikh et al., 2007; Shenvi et al., 2008). The functionalization of the unactivated angular C-10 methyl group is achieved by remote functionalization (Heusler et al., 1964; Reese, 2001). During our synthesis of diverse B-homo-steroids the C-19-hydroxy-steroid (I) was isolated as an intermediate (Kranz et al., 2011). The C/D and D/E rings in C₂₃H₃₄O₄ are trans fused and the A/B ring possesses an anti fusion. The A ring and the C ring adopt a chair conformation, while the other six membered B ring displays a half chair conformation (Fig. 1). In the five membered ring, the atoms show an envelope conformation and C14/C15/C16/C17 are nearly coplanar while the C13 deviates from the plane by 0.726 (2) Å. The C(5)–C(10)–C(19)–O(3) torsion angle is -165.71 (16)° and the torsion angles C(4)–C(5)–C(10)–C(1) with -45.0 (2)°, C(1)–C(10)–C(9)–C(11) with 68.3 (2)° and C(8)–C(14)–C(13)–C(12) with -58.9 (2)° are within the average range (Allen, 2002). The molecules are linked by O–H···O hydrogen bonds between the C19 hydroxy group of one steroid to the ester carbonyl oxygen of the next steroid, forming chain networks along the b axis. These chain networks generate layer structures parallel to the c axis (Fig. 2).

Experimental

The title compound C₂₃H₃₄O₄ was prepared in 3 steps starting from commercial pregnenolone-acetate (Kranz et al., 2011).