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Acta Crystallogr Sect E Struct Rep Online. 2010 November 1; 66(Pt 11): o2894.
Published online 2010 October 23. doi:  10.1107/S160053681004033X
PMCID: PMC3009298

17β-Hy­droxy-17α-(hy­droxy­meth­yl)estr-4-en-3-one

Abstract

The title compound, C19H28O3, the fungal-transformed metabolite of the steroid methyl­oestrenol contains four fused rings A, B, C and D. Ring A adopts a half-chair and the trans-fused rings B and C adopt chair confirmations; the five-membered D ring is folded like an envelope. In the crystal, adjacent mol­ecules are linked by O—H(...)Ocarbon­yl and O—H(...)Ohy­droxy hydrogen bonds into a layer structure.

Related literature

For the synthesis, see: Hübner & Ponsold (1983 [triangle]); Ponsold et al. (1978a [triangle],b [triangle]); Szilagyi et al. (1984 [triangle]). For the crystal structures of three modified17b-hy­droxy-3-oxo-17a-(halogen/pseudo­halogenometh­yl)-estra-4-ene progestagens, see: Beck et al. (1986a [triangle],b [triangle],c [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2894-scheme1.jpg

Experimental

Crystal data

  • C19H28O3
  • M r = 304.41
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2894-efi1.jpg
  • a = 9.9696 (6) Å
  • b = 12.5858 (8) Å
  • c = 13.3968 (8) Å
  • V = 1680.97 (18) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.08 mm−1
  • T = 295 K
  • 0.35 × 0.20 × 0.10 mm

Data collection

  • Bruker SMART APEX CCD diffractometer
  • 11685 measured reflections
  • 2203 independent reflections
  • 1799 reflections with I > 2σ(I)
  • R int = 0.047

Refinement

  • R[F 2 > 2σ(F 2)] = 0.047
  • wR(F 2) = 0.119
  • S = 1.11
  • 2203 reflections
  • 207 parameters
  • 2 restraints
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.19 e Å−3
  • Δρmin = −0.28 e Å−3

Data collection: SMART (Bruker, 2003 [triangle]); cell refinement: SAINT (Bruker, 2003 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: X-SEED (Barbour, 2001 [triangle]); software used to prepare material for publication: publCIF (Westrip, 2010 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681004033X/hb5675sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053681004033X/hb5675Isup2.hkl

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

Acknowledgments

We thank the Higher Education Commission of Pakistan for supporting this study through an Indigenous Research Grant for PhDs, and the University of Malaya for supporting this study.

supplementary crystallographic information

Comment

Structure modification by using microbes, cells and fungi, i.e., biotransfromation, is an excellent method for understanding the structure-activity relationship of bioactive compounds and drugs. In this study, a new compound was isolated when the estrogen drug methyloestrenolone was incubated with Aspergillus niger. This study represents the first report of the biotransformation of methyloestrenolone; the compound is 17α-(hydroxymethyl)-estr-4-en-17β-ol-3-one (Scheme I, Fig. 1). Adjacent molecules are linked by OH···Ocarbonyl and OH···Ohydroxy hydrogen bonds into a layer structure (Fig. 2). Bond dimensions are similar to those found in three other 17β-hydroxy-3-oxo-17α-(halogen/pseudohalogenomethyl)-estra-4-ene progestagens (Beck et al., 1986a,b,c).

The title compound has been obtained by conventional chemical synthesis (Hübner & Ponsold, 1983; Ponsold et al., 1978a, 1978b; Szilagyi et al., 1984).

Experimental

Culture preparation

In 4 L water were dissolved glucose (40 g), peptone (20 g), yeast extract (12 g), potassium dihydrogen phosphate (20 g), sodium chloride (20 g) and glycerol (40 ml). The solution was distributed among 40 conical flasks (100 ml each); the mouths of the flasks were covered with cotton wool. The flasks were then heated at 374 K for 15 minutes. The spores of Aspergillus niger were transferred from slants grown on saboraud dextrose agar. The flasks were left on rotary shaker until there was sufficient growth of the spores. Methyloestrenolone (1 g) was distributed equally among the flasks in the form of its solution in acetone (20 ml, 0.5 ml per flask).

Fermentation of methyloestrenolone

Methyloestrenolone was also incubated with a liquid phase culture of Aspergillus niger (4 L) for 14 days. The biomass was separated by filtration and the filtrate extracted with dichloromethane The extract was dried with sodium sulfate; the solvent was evaporated to leave about 3 g of a brown gummy material. This was subjected to fractionation on a silica gel column with petroleum ether–ethyl acetate gradient solvent system. The fractions were subjected to size exclusion HPLC (GS-320, methanol, 35 minute retention time). Evaporation of the solvent gave the title compound as colorless prisms of (I).

Refinement

Carbon-bound H-atoms were placed in calculated positions (C—H 0.93 to 0.98 Å) and were included in the refinement in the riding model approximation, with U(H) set to 1.2 to 1.5U(C).

The hydroxy H-atoms were located in a difference Fourier map, and were refined with a distance restraint of O–H 0.84±0.01 Å; their temperature factors were freely refined.

The absolute configuration was assumed to be that of methyloestrenolone itself; 1656 Friedel pairs were merged.

Figures

Fig. 1.
The molecuylar structure of (I) at the 50% probability level; hydrogen atoms are drawn as spheres of arbitrary radius.
Fig. 2.
Layer structure.

Crystal data

C19H28O3F(000) = 664
Mr = 304.41Dx = 1.203 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 2043 reflections
a = 9.9696 (6) Åθ = 2.5–21.3°
b = 12.5858 (8) ŵ = 0.08 mm1
c = 13.3968 (8) ÅT = 295 K
V = 1680.97 (18) Å3Prism, colorless
Z = 40.35 × 0.20 × 0.10 mm

Data collection

Bruker SMART APEX CCD diffractometer1799 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.047
graphiteθmax = 27.5°, θmin = 2.2°
ω scansh = −12→12
11685 measured reflectionsk = −15→16
2203 independent reflectionsl = −17→13

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.047Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.119H atoms treated by a mixture of independent and constrained refinement
S = 1.11w = 1/[σ2(Fo2) + (0.0591P)2 + 0.0486P] where P = (Fo2 + 2Fc2)/3
2203 reflections(Δ/σ)max = 0.001
207 parametersΔρmax = 0.19 e Å3
2 restraintsΔρmin = −0.28 e Å3

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
O10.5961 (3)1.11961 (17)1.13914 (18)0.0682 (7)
O20.39264 (19)0.32100 (16)1.04677 (15)0.0492 (5)
O30.6378 (2)0.26561 (14)0.97416 (16)0.0462 (5)
C10.6147 (3)0.8388 (2)1.17666 (19)0.0464 (7)
H1A0.51760.83851.17220.056*
H1B0.64080.79061.22970.056*
C20.6631 (3)0.9507 (2)1.2017 (2)0.0506 (7)
H2A0.62350.97341.26430.061*
H2B0.75980.95031.20970.061*
C30.6256 (3)1.0271 (2)1.1211 (2)0.0451 (6)
C40.6340 (3)0.9862 (2)1.0191 (2)0.0420 (6)
H40.61851.03280.96660.050*
C50.6628 (2)0.88515 (19)0.99789 (19)0.0356 (6)
C60.6928 (3)0.8510 (2)0.89256 (19)0.0438 (7)
H6A0.78930.84800.88390.053*
H6B0.65840.90440.84710.053*
C70.6336 (3)0.74360 (19)0.86388 (19)0.0445 (7)
H7A0.66890.72200.79950.053*
H7B0.53700.74990.85790.053*
C80.6673 (3)0.65901 (18)0.94171 (18)0.0333 (5)
H80.76510.65320.94680.040*
C90.6117 (3)0.69403 (18)1.04371 (16)0.0310 (5)
H90.51530.70641.03500.037*
C100.6743 (3)0.80063 (18)1.07782 (17)0.0329 (5)
H100.77010.78791.08900.040*
C110.6269 (3)0.60786 (18)1.12419 (19)0.0393 (6)
H11A0.72090.60151.14180.047*
H11B0.57850.62981.18350.047*
C120.5748 (3)0.49914 (18)1.09091 (16)0.0342 (6)
H12A0.59400.44701.14230.041*
H12B0.47820.50261.08260.041*
C130.6389 (2)0.46399 (18)0.99316 (17)0.0306 (5)
C140.6106 (3)0.55026 (19)0.91475 (17)0.0336 (5)
H140.51290.55840.91160.040*
C150.6536 (4)0.4988 (2)0.8161 (2)0.0542 (8)
H15A0.74880.50870.80440.065*
H15B0.60400.52850.76040.065*
C160.6199 (3)0.3807 (2)0.8303 (2)0.0525 (7)
H16A0.69730.33730.81400.063*
H16B0.54660.36050.78670.063*
C170.5796 (2)0.36350 (19)0.94063 (18)0.0343 (5)
C180.7903 (3)0.4452 (2)1.0088 (2)0.0494 (7)
H18B0.82910.50601.04120.074*
H18C0.83290.43450.94540.074*
H18D0.80330.38351.04980.074*
C190.4282 (3)0.3522 (2)0.9490 (2)0.0419 (6)
H19A0.38570.41950.93310.050*
H19B0.39680.29960.90160.050*
H20.3200 (19)0.288 (2)1.041 (2)0.065 (10)*
H30.595 (4)0.242 (3)1.023 (2)0.098 (16)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0825 (17)0.0374 (11)0.0847 (16)0.0077 (11)0.0139 (13)−0.0098 (11)
O20.0399 (11)0.0470 (11)0.0606 (13)−0.0140 (9)0.0059 (9)0.0023 (9)
O30.0407 (11)0.0276 (9)0.0702 (15)0.0056 (8)0.0070 (10)0.0029 (9)
C10.0666 (19)0.0341 (14)0.0384 (14)−0.0083 (13)0.0058 (13)−0.0056 (11)
C20.064 (2)0.0374 (14)0.0500 (17)−0.0081 (14)0.0078 (15)−0.0113 (12)
C30.0394 (14)0.0333 (14)0.0627 (17)−0.0052 (12)0.0067 (13)−0.0055 (12)
C40.0438 (15)0.0303 (13)0.0520 (15)−0.0035 (11)−0.0025 (13)0.0058 (11)
C50.0342 (13)0.0307 (12)0.0418 (14)−0.0074 (10)0.0000 (11)0.0038 (10)
C60.0580 (17)0.0341 (14)0.0395 (14)−0.0086 (13)0.0047 (12)0.0086 (11)
C70.0672 (19)0.0362 (14)0.0300 (13)−0.0089 (14)−0.0019 (13)0.0038 (10)
C80.0377 (12)0.0302 (12)0.0319 (12)−0.0034 (10)0.0021 (10)0.0003 (9)
C90.0335 (12)0.0270 (11)0.0326 (12)−0.0035 (10)0.0008 (10)0.0013 (9)
C100.0375 (13)0.0287 (12)0.0325 (13)−0.0033 (10)−0.0022 (10)−0.0002 (9)
C110.0582 (17)0.0310 (12)0.0288 (12)−0.0027 (12)−0.0022 (12)0.0035 (9)
C120.0461 (15)0.0276 (12)0.0291 (12)−0.0033 (11)0.0013 (10)0.0052 (9)
C130.0276 (12)0.0288 (11)0.0354 (13)−0.0004 (10)0.0002 (10)−0.0006 (9)
C140.0392 (13)0.0312 (12)0.0305 (12)−0.0036 (11)0.0015 (10)−0.0007 (9)
C150.085 (2)0.0407 (15)0.0373 (15)−0.0107 (16)0.0157 (15)−0.0060 (12)
C160.071 (2)0.0397 (15)0.0470 (16)−0.0072 (15)0.0116 (15)−0.0112 (13)
C170.0348 (12)0.0263 (12)0.0417 (13)0.0010 (10)0.0006 (11)−0.0003 (10)
C180.0350 (15)0.0390 (15)0.074 (2)0.0006 (12)−0.0044 (14)−0.0035 (14)
C190.0380 (13)0.0345 (14)0.0532 (15)−0.0042 (11)−0.0071 (12)0.0012 (12)

Geometric parameters (Å, °)

O1—C31.225 (3)C9—C101.549 (3)
O2—C191.413 (3)C9—H90.9800
O2—H20.84 (3)C10—H100.9800
O3—C171.434 (3)C11—C121.530 (3)
O3—H30.84 (3)C11—H11A0.9700
C1—C21.526 (4)C11—H11B0.9700
C1—C101.529 (3)C12—C131.523 (3)
C1—H1A0.9700C12—H12A0.9700
C1—H1B0.9700C12—H12B0.9700
C2—C31.493 (4)C13—C141.537 (3)
C2—H2A0.9700C13—C181.543 (3)
C2—H2B0.9700C13—C171.563 (3)
C3—C41.463 (4)C14—C151.533 (3)
C4—C51.334 (4)C14—H140.9800
C4—H40.9300C15—C161.536 (4)
C5—C61.505 (4)C15—H15A0.9700
C5—C101.514 (3)C15—H15B0.9700
C6—C71.524 (3)C16—C171.546 (4)
C6—H6A0.9700C16—H16A0.9700
C6—H6B0.9700C16—H16B0.9700
C7—C81.527 (3)C17—C191.520 (3)
C7—H7A0.9700C18—H18B0.9600
C7—H7B0.9700C18—H18C0.9600
C8—C141.524 (3)C18—H18D0.9600
C8—C91.539 (3)C19—H19A0.9700
C8—H80.9800C19—H19B0.9700
C9—C111.537 (3)
C19—O2—H2106 (2)C12—C11—H11A108.9
C17—O3—H3110 (3)C9—C11—H11A108.9
C2—C1—C10111.0 (2)C12—C11—H11B108.9
C2—C1—H1A109.4C9—C11—H11B108.9
C10—C1—H1A109.4H11A—C11—H11B107.8
C2—C1—H1B109.4C13—C12—C11111.6 (2)
C10—C1—H1B109.4C13—C12—H12A109.3
H1A—C1—H1B108.0C11—C12—H12A109.3
C3—C2—C1110.9 (2)C13—C12—H12B109.3
C3—C2—H2A109.5C11—C12—H12B109.3
C1—C2—H2A109.5H12A—C12—H12B108.0
C3—C2—H2B109.5C12—C13—C14107.80 (19)
C1—C2—H2B109.5C12—C13—C18109.8 (2)
H2A—C2—H2B108.1C14—C13—C18112.4 (2)
O1—C3—C4122.2 (3)C12—C13—C17117.6 (2)
O1—C3—C2122.0 (3)C14—C13—C17101.23 (18)
C4—C3—C2115.7 (2)C18—C13—C17107.9 (2)
C5—C4—C3123.2 (3)C8—C14—C15118.7 (2)
C5—C4—H4118.4C8—C14—C13113.9 (2)
C3—C4—H4118.4C15—C14—C13103.9 (2)
C4—C5—C6121.0 (2)C8—C14—H14106.5
C4—C5—C10122.3 (2)C15—C14—H14106.5
C6—C5—C10116.6 (2)C13—C14—H14106.5
C5—C6—C7114.4 (2)C14—C15—C16103.9 (2)
C5—C6—H6A108.7C14—C15—H15A111.0
C7—C6—H6A108.7C16—C15—H15A111.0
C5—C6—H6B108.7C14—C15—H15B111.0
C7—C6—H6B108.7C16—C15—H15B111.0
H6A—C6—H6B107.6H15A—C15—H15B109.0
C6—C7—C8111.2 (2)C15—C16—C17108.1 (2)
C6—C7—H7A109.4C15—C16—H16A110.1
C8—C7—H7A109.4C17—C16—H16A110.1
C6—C7—H7B109.4C15—C16—H16B110.1
C8—C7—H7B109.4C17—C16—H16B110.1
H7A—C7—H7B108.0H16A—C16—H16B108.4
C14—C8—C7112.5 (2)O3—C17—C19107.4 (2)
C14—C8—C9109.51 (19)O3—C17—C16108.3 (2)
C7—C8—C9109.1 (2)C19—C17—C16110.0 (2)
C14—C8—H8108.5O3—C17—C13113.66 (19)
C7—C8—H8108.5C19—C17—C13114.7 (2)
C9—C8—H8108.5C16—C17—C13102.65 (19)
C11—C9—C8112.66 (19)C13—C18—H18B109.5
C11—C9—C10111.39 (19)C13—C18—H18C109.5
C8—C9—C10111.39 (19)H18B—C18—H18C109.5
C11—C9—H9107.0C13—C18—H18D109.5
C8—C9—H9107.0H18B—C18—H18D109.5
C10—C9—H9107.0H18C—C18—H18D109.5
C5—C10—C1111.2 (2)O2—C19—C17110.1 (2)
C5—C10—C9111.69 (19)O2—C19—H19A109.6
C1—C10—C9111.8 (2)C17—C19—H19A109.6
C5—C10—H10107.3O2—C19—H19B109.6
C1—C10—H10107.3C17—C19—H19B109.6
C9—C10—H10107.3H19A—C19—H19B108.2
C12—C11—C9113.1 (2)
C10—C1—C2—C358.7 (3)C11—C12—C13—C1865.7 (3)
C1—C2—C3—O1145.9 (3)C11—C12—C13—C17−170.4 (2)
C1—C2—C3—C4−37.6 (4)C7—C8—C14—C1559.1 (3)
O1—C3—C4—C5−178.4 (3)C9—C8—C14—C15−179.4 (2)
C2—C3—C4—C55.1 (4)C7—C8—C14—C13−178.2 (2)
C3—C4—C5—C6−169.7 (3)C9—C8—C14—C13−56.7 (3)
C3—C4—C5—C107.0 (4)C12—C13—C14—C860.2 (3)
C4—C5—C6—C7−140.6 (3)C18—C13—C14—C8−60.9 (3)
C10—C5—C6—C742.5 (3)C17—C13—C14—C8−175.7 (2)
C5—C6—C7—C8−50.0 (3)C12—C13—C14—C15−169.2 (2)
C6—C7—C8—C14−179.5 (2)C18—C13—C14—C1569.7 (3)
C6—C7—C8—C958.8 (3)C17—C13—C14—C15−45.2 (2)
C14—C8—C9—C1150.0 (3)C8—C14—C15—C16161.0 (2)
C7—C8—C9—C11173.5 (2)C13—C14—C15—C1633.4 (3)
C14—C8—C9—C10175.97 (19)C14—C15—C16—C17−8.6 (3)
C7—C8—C9—C10−60.5 (3)C15—C16—C17—O3−139.3 (3)
C4—C5—C10—C114.6 (4)C15—C16—C17—C19103.6 (3)
C6—C5—C10—C1−168.6 (2)C15—C16—C17—C13−18.8 (3)
C4—C5—C10—C9140.3 (2)C12—C13—C17—O3−87.4 (3)
C6—C5—C10—C9−42.9 (3)C14—C13—C17—O3155.4 (2)
C2—C1—C10—C5−46.5 (3)C18—C13—C17—O337.3 (3)
C2—C1—C10—C9−172.2 (2)C12—C13—C17—C1936.6 (3)
C11—C9—C10—C5178.6 (2)C14—C13—C17—C19−80.5 (2)
C8—C9—C10—C551.9 (3)C18—C13—C17—C19161.3 (2)
C11—C9—C10—C1−56.0 (3)C12—C13—C17—C16155.8 (2)
C8—C9—C10—C1177.2 (2)C14—C13—C17—C1638.7 (2)
C8—C9—C11—C12−50.1 (3)C18—C13—C17—C16−79.5 (3)
C10—C9—C11—C12−176.1 (2)O3—C17—C19—O253.7 (3)
C9—C11—C12—C1354.1 (3)C16—C17—C19—O2171.4 (2)
C11—C12—C13—C14−56.9 (3)C13—C17—C19—O2−73.6 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O2—H2···O3i0.84 (3)1.95 (3)2.779 (3)171 (3)
O3—H3···O1ii0.84 (3)2.18 (3)2.904 (3)144 (4)

Symmetry codes: (i) x−1/2, −y+1/2, −z+2; (ii) x, y−1, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HB5675).

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