11α,15α-Dihy­droxy­androst-4-ene-3,17-dione

Yan-Bing Shen; Min Wang; Qi-Kun Liang; Jian-Mei Luo

doi:10.1107/S1600536811038608

. 2011 Sep 30;67(Pt 10):o2752. doi: 10.1107/S1600536811038608

11α,15α-Dihydroxyandrost-4-ene-3,17-dione

Yan-Bing Shen ^a, Min Wang ^a,^*, Qi-Kun Liang ^a, Jian-Mei Luo ^a

PMCID: PMC3201477 PMID: 22058810

Abstract

The title compound, C₁₉H₂₆O₄, was biotransformed from androstenedione. In the crystal, intermolecular O—H⋯O hydrogen bonds link molecules into a corrugated sheet, which lies parallel to the ab plane. Ring A has a slightly distorted half-chair conformation, rings B and C adopt chair conformations, while the cyclopentane ring D adopts a 14α-envelope conformation.

Related literature

For related structures, see: Galdecki et al. (1990 ▶); Thamotharan et al. (2004 ▶); Vasuki et al. (2002 ▶). For details of biotransformation, see: Ahmad et al. (1992 ▶); Kollerov et al. (2008 ▶); Malaviya & Gomes (2008 ▶); Perez et al. (2006 ▶). For conformational analysis, see Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₉H₂₆O₄
M _r = 318.40
Orthorhombic,
a = 7.8716 (8) Å
b = 12.2725 (12) Å
c = 17.2100 (16) Å
V = 1662.6 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 113 K
0.22 × 0.18 × 0.12 mm

Data collection

Rigaku Saturn 724CCD diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005 ▶) T _min = 0.981, T _max = 0.990
17662 measured reflections
2275 independent reflections
2050 reflections with I > 2σ(I)
R _int = 0.047

Refinement

R[F ² > 2σ(F ²)] = 0.037
wR(F ²) = 0.081
S = 1.03
2275 reflections
218 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: CrystalClear (Rigaku, 2005 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811038608/lw2070sup1.cif

e-67-o2752-sup1.cif^{(21.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811038608/lw2070Isup2.hkl

e-67-o2752-Isup2.hkl^{(111.9KB, 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—H3⋯O2ⁱ	0.88 (3)	1.94 (3)	2.800 (2)	164 (3)
O2—H2⋯O1ⁱⁱ	0.81 (3)	1.95 (3)	2.7600 (19)	180 (3)

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 21076158), the Program for New Century Excellent Talents in Universities (No. NCET-08–0911) and the Foundation for Excellent Doctoral Dissertations of Tianjin University of Science and Technology in 2010 (No. B201001).

supplementary crystallographic information

Comment

Androst-4-ene-3,17-dione (AD) is the important intermediate in the pharmaceutical industry (Perez et al., 2006; Kollerov et al. 2008). The production of several high value steroid drugs is mostly derived from key compounds such as AD by chemical synthesis (Ahmad et al., 1992; Malaviya & Gomes, 2008).

The structure of the title compound is depicted in Fig. 1. The 11α,15α-dihydroxy-androstenedione has three six-membered rings (A/B/C) and one five-membered rings (D). Ring A has a slightly distorted half-chair conformation. Rings B and C adopt chair conformations, while the cyclopentane ring D adopts a 14α-envelope conformation. The torsion angle C8—C9—C11—O2 = 162.83 (13), indicates that the 11-hydroxy has an α configuration. The 15-hydroxy has an α configuration with the torsion angle C13—C14—C15—O3 = -160.83 (14)°. The bond lengths and angles are within normal ranges (Thamotharan et al., 2004; Vasuki, et al., 2002; Galdecki et al., 1990).

Two types of intermolecular hydrogen bonds contribute to the formation of a two-dimensional corrugated sheet lying parallel to the ab-plane, Figure 2. The O3 hydroxyl hydrogen forms a hydrogen bond to hydroxyl atom O2 at (1-x,y,z) by unit translation along the a-axis. Hydroxyl oxygen O2 forms a hydrogen bond to the screw-related carbonyl atom O1 at (1-x,-1/2+y,1/2-z), Table 1.

Experimental

Reagents: Colletotrichum lini AS3. 4486 was obtained from Institute of Microbiology, Chinese Academy of Sciences and maintained on Potato Dextrose Agar at 4°C. Androst-4-en-3,17-dione was obtained from Tianjin Pharmaceutical Company.

Cultures Protocol: Colletotrichum lini AS3. 4486 was cultivated in shake flasks in two consecutive cultivation steps: 72 h for seed culture and 24 h for cell cultivation. Seed medium comprised glucose 30 g/L, corn steep liquor 10 g/L and tap water (pH 7.0). Cell cultivation medium comprised glucose 3 g/L, corn steep liquor 10 g/L, soy meal 10 g/L, NaNO₃ 2 g/L, KH₂PO₄, 1 g/L, K₂HPO₄, 2 g/L, MgSO₄.7H₂O 0.5g/L, KCl, 0.5g/L, FeSO₄.7H₂O, 0.02 g/L, (pH 7.0). Cells were grown in 250 ml shake flasks containing 50 ml culture medium on a rotary shaker (200 r/min) at 25°C using 10% (v/v) of the seed culture as inoculum.

Biotransformation: 50 mg of the androst-4-en-3,17-dione dissolved in 1 ml of ethanol was added to the culture after 24 h for growth and the reaction was allowed to proceed for 72 h. The mycelium was then removed by filtration.

Separation and purification: The biomass and the broth were extracted separately with EtOAc. All extracts were combined and dried (anhydr. MgSO₄). The solvents after filtration were evaporated under reduced pressure. The crude extracts were purified by Si gel column using dichloromethane/ether/methanol (25:2:1, v/v/v). The white powder was diffused with n-hexane/acetone at room temperature. Colorless prismatic crystals suitable for X-ray analysis were obtained.