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In the title compound, C19H28O3, the ester linkage in ring A is equatorial. The six-membered rings A and B have chair conformations, but ring C can be better described as a half-chair. The five-membered ring D adopts a 14α-envelope conformation. The A/B, B/C and C/D ring junctions are all trans. The packing of the mol­ecules is assumed to be dictated mainly by intermolecular hydrogen bonds. There is an intramolecular C—H...O interaction between the O11 atom of the epoxy group and the methyl C18 group.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536800018845/cf6010sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536800018845/cf6010Isup2.hkl
Contains datablock I

CCDC reference: 155880

Key indicators

  • Single-crystal X-ray study
  • T = 293 K
  • Mean [sigma](C-C) = 0.003 Å
  • R factor = 0.036
  • wR factor = 0.103
  • Data-to-parameter ratio = 10.0

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


Yellow Alert Alert Level C:
STRVAL_01 From the CIF: _refine_ls_abs_structure_Flack -0.300 From the CIF: _refine_ls_abs_structure_Flack_su 0.300 Alert C Flack parameter is too small General Notes
REFLT_03 From the CIF: _diffrn_reflns_theta_max 69.10 From the CIF: _reflns_number_total 2031 Count of symmetry unique reflns 1777 Completeness (_total/calc) 114.29% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 254 Fraction of Friedel pairs measured 0.143 Are heavy atom types Z>Si present no WARNING: CuKa measured Friedel data can be used to determine absolute structure in a light-atom study only if the Friedel fraction is large.
0 Alert Level A = Potentially serious problem
0 Alert Level B = Potential problem
1 Alert Level C = Please check

Comment top

Corticosteroids have demonstrated substantial topical anti-inflamatory potency. In particular, betamethasone 17-benzoate has been in clinical practice for a long time (Lutsky et al., 1979). The strategy and importance for the synthesis of these compounds have antecedents in similar structures, with anabolic and/or androgenic activity, replacing the positions 9α and 11β with fluorine and hydroxyl, respectively (Shapiro et al., 1987). An example of this is 9α-fluoro-11β,17α-dihydroxy-17α-methyl-4-androsten-3-one (halotestin), a commercial compound 20 times more androgenic and 10 times more anabolic than methyltestosterone. In connection with our studies on the synthesis and characterization of bioactive steroids, the structure of the title compound, (I), could allow us to predict the possibility of presenting/displaying anabolic and/or androgenic properties. The absolute configuration was assumed to be the same as that predicted beforehand from the synthesis route. Fig. 1 shows the molecular structure of (I), with the corresponding numbering scheme. The C3—O3 bond of the hydroxy group is equatorially oriented and (-)antiperiplanar to the C3—C4 bond. The presence of OH bonded to C3 does not disturb the chair conformation in the ring A of the steroid nucleus. Ring A has a highly symmetrical chair conformation with all asymmetry parameters (Duax et al., 1976) below 4.3 (3)°. The average magnitude of the torsion angles is 55.08 (10)°. Ring B displays a chair conformation, as expected (Pfieffer et al., 1985), but this is not the case for ring C, which has a half-chair conformation. The five-membered ring D adopts a 14α-envelope conformation (Altona et al., 1968). The A/B, B/C and C/D ring junctions are all trans. Bond distances and valence angles are close to expected values (Honda et al., 1996). The packing of the molecules is assumed to be dictated mainly by intermolecular O3—H3a···O17 hydrogen bonds. There is an intramolecular C—H···O interaction between the O11 atom of the epoxy group and the methyl C18 group (Taylor & Kennard, 1982).

Experimental top

The synthesis of the title compound is described by Ruíz (1997). Crystals (m.p. 529 K) were grown by slow evaporation from ethanol.

Refinement top

H atoms were calculated geometrically and included in the refinement, but were constrained to ride on their parent atoms. The isotropic displacement parameters of the H atoms were fixed to 1.3Ueq of their parent atoms.

Computing details top

Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: DIAMOND (Bergerhoff, 1996); software used to prepare material for publication: PLATON (Spek, 1990), PARST (Nardelli, 1983, 1995) and PARSTCIF (Nardelli, 1991).

Figures top
[Figure 1] Fig. 1. Plot showing the atomic numbering scheme for the title compound. Displacement ellipsoids are drawn at 50% probability level for non-H atoms. H atoms have been omitted for clarity.
9β,11β-Epoxy-3β-hydroxy-5α-androstan-17-one top
Crystal data top
C19H28O3Dx = 1.234 Mg m3
Mr = 304.41Melting point: 236 K
Orthorhombic, P212121Cu Kα radiation, λ = 1.54180 Å
Hall symbol: P 2ac 2abCell parameters from 40 reflections
a = 7.3171 (3) Åθ = 10.5–28.0°
b = 10.6462 (6) ŵ = 0.64 mm1
c = 21.0401 (14) ÅT = 293 K
V = 1639.01 (16) Å3Prism, colourless
Z = 40.64 × 0.46 × 0.28 mm
F(000) = 664
Data collection top
Siemens P4 four-circle
diffractometer
1987 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.043
Graphite monochromatorθmax = 69.1°, θmin = 4.2°
ω/2θ scansh = 81
Absorption correction: ψ scan
(North et al., 1968)
k = 112
Tmin = 0.615, Tmax = 0.835l = 125
2214 measured reflections3 standard reflections every 100 reflections
2031 independent reflections intensity decay: none
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.036 w = 1/[σ2(Fo2) + (0.0626P)2 + 0.3007P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.103(Δ/σ)max = 0.006
S = 1.07Δρmax = 0.21 e Å3
2031 reflectionsΔρmin = 0.16 e Å3
203 parametersExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.0148 (11)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983); 388 Friedel pairs
Secondary atom site location: difference Fourier mapAbsolute structure parameter: 0.3 (3)
Crystal data top
C19H28O3V = 1639.01 (16) Å3
Mr = 304.41Z = 4
Orthorhombic, P212121Cu Kα radiation
a = 7.3171 (3) ŵ = 0.64 mm1
b = 10.6462 (6) ÅT = 293 K
c = 21.0401 (14) Å0.64 × 0.46 × 0.28 mm
Data collection top
Siemens P4 four-circle
diffractometer
1987 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)
Rint = 0.043
Tmin = 0.615, Tmax = 0.8353 standard reflections every 100 reflections
2214 measured reflections intensity decay: none
2031 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.036H-atom parameters constrained
wR(F2) = 0.103Δρmax = 0.21 e Å3
S = 1.07Δρmin = 0.16 e Å3
2031 reflectionsAbsolute structure: Flack (1983); 388 Friedel pairs
203 parametersAbsolute structure parameter: 0.3 (3)
0 restraints
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.2916 (3)0.8888 (2)0.27104 (10)0.0416 (5)
H1A0.40130.88410.29680.052*
H1B0.26070.97680.26580.052*
C20.3310 (3)0.8316 (3)0.20555 (10)0.0491 (6)
H2A0.37030.74520.21060.061*
H2B0.42910.87780.18520.061*
C30.1616 (3)0.8359 (2)0.16399 (10)0.0410 (5)
H30.13150.92420.15600.051*
O30.1879 (2)0.77530 (19)0.10416 (7)0.0545 (5)
H3A0.28930.79290.09020.068*
C40.0005 (3)0.7754 (2)0.19632 (9)0.0403 (5)
H4A0.10750.78780.17030.050*
H4B0.02210.68570.19950.050*
C50.0354 (3)0.8281 (2)0.26268 (9)0.0339 (4)
H50.06460.91720.25710.042*
C60.2000 (3)0.7685 (2)0.29433 (10)0.0432 (5)
H6A0.17300.68180.30500.054*
H6B0.30310.76920.26530.054*
C70.2479 (3)0.8407 (2)0.35406 (10)0.0396 (5)
H7A0.28900.92390.34190.050*
H7B0.34950.79880.37480.050*
C80.0917 (3)0.85474 (18)0.40246 (9)0.0318 (4)
H80.08190.77660.42680.040*
C90.0962 (2)0.88276 (18)0.37157 (9)0.0304 (4)
C100.1351 (3)0.82229 (19)0.30603 (9)0.0316 (4)
C110.2053 (3)0.9902 (2)0.39730 (9)0.0356 (5)
H110.28851.02980.36680.044*
O110.25030 (19)0.86249 (14)0.41395 (7)0.0387 (4)
C120.1480 (3)1.07242 (19)0.45184 (10)0.0358 (5)
H12A0.25361.09050.47820.045*
H12B0.10221.15150.43540.045*
C130.0006 (3)1.01079 (17)0.49239 (9)0.0320 (4)
C140.1469 (2)0.96026 (18)0.44767 (10)0.0321 (4)
H140.17881.03120.42010.040*
C150.3143 (3)0.9410 (2)0.49062 (11)0.0432 (5)
H15A0.30260.86550.51600.054*
H15B0.42610.93660.46600.054*
C160.3094 (3)1.0593 (2)0.53220 (12)0.0472 (5)
H16A0.35241.04070.57480.059*
H16B0.38571.12470.51410.059*
C170.1121 (3)1.09998 (19)0.53352 (10)0.0362 (5)
O170.0528 (2)1.18838 (14)0.56381 (8)0.0472 (4)
C180.0771 (3)0.9139 (2)0.54002 (10)0.0416 (5)
H18A0.02200.87630.56310.052*
H18B0.14270.84990.51740.052*
H18C0.15810.95520.56920.052*
C190.1905 (4)0.6848 (2)0.31999 (11)0.0484 (6)
H19A0.31020.68330.33870.061*
H19B0.10420.64810.34890.061*
H19C0.19140.63780.28110.061*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0309 (10)0.0589 (13)0.0349 (10)0.0070 (10)0.0005 (9)0.0052 (11)
C20.0354 (11)0.0732 (16)0.0385 (11)0.0060 (12)0.0012 (9)0.0063 (13)
C30.0449 (12)0.0477 (11)0.0303 (10)0.0033 (11)0.0005 (9)0.0037 (10)
O30.0518 (9)0.0773 (12)0.0346 (8)0.0139 (10)0.0060 (7)0.0139 (9)
C40.0387 (10)0.0493 (11)0.0330 (10)0.0039 (10)0.0035 (9)0.0013 (10)
C50.0325 (10)0.0382 (9)0.0309 (10)0.0022 (9)0.0058 (8)0.0009 (9)
C60.0367 (11)0.0546 (13)0.0382 (10)0.0129 (11)0.0048 (9)0.0058 (11)
C70.0308 (9)0.0510 (12)0.0371 (10)0.0102 (10)0.0006 (8)0.0020 (11)
C80.0332 (9)0.0310 (9)0.0312 (9)0.0047 (8)0.0007 (8)0.0008 (9)
C90.0282 (9)0.0339 (9)0.0291 (9)0.0010 (8)0.0029 (8)0.0026 (9)
C100.0295 (9)0.0350 (9)0.0303 (9)0.0014 (8)0.0037 (7)0.0013 (9)
C110.0326 (9)0.0415 (10)0.0327 (9)0.0054 (9)0.0016 (8)0.0003 (9)
O110.0363 (7)0.0450 (8)0.0349 (7)0.0050 (7)0.0099 (6)0.0035 (7)
C120.0360 (9)0.0363 (9)0.0352 (10)0.0067 (9)0.0033 (8)0.0018 (9)
C130.0345 (9)0.0291 (8)0.0325 (10)0.0027 (8)0.0033 (8)0.0018 (9)
C140.0316 (9)0.0304 (8)0.0343 (10)0.0023 (8)0.0026 (8)0.0028 (9)
C150.0369 (10)0.0421 (11)0.0506 (12)0.0055 (9)0.0085 (10)0.0094 (11)
C160.0429 (11)0.0440 (11)0.0547 (13)0.0006 (10)0.0080 (11)0.0115 (12)
C170.0430 (10)0.0327 (9)0.0328 (10)0.0059 (9)0.0032 (8)0.0010 (10)
O170.0498 (9)0.0435 (8)0.0482 (8)0.0046 (7)0.0095 (7)0.0146 (8)
C180.0523 (11)0.0409 (10)0.0317 (9)0.0104 (11)0.0034 (9)0.0029 (10)
C190.0640 (14)0.0413 (11)0.0400 (11)0.0140 (12)0.0078 (12)0.0019 (11)
Geometric parameters (Å, º) top
C1—C21.534 (3)C9—C111.496 (3)
C1—C101.534 (3)C9—C101.548 (3)
C2—C31.517 (3)C10—C191.547 (3)
C3—O31.428 (3)C11—O111.442 (3)
C3—C41.506 (3)C11—C121.503 (3)
C4—C51.527 (3)C12—C131.524 (3)
C5—C61.516 (3)C13—C171.526 (3)
C5—C101.546 (2)C13—C141.530 (3)
C6—C71.514 (3)C13—C181.543 (3)
C7—C81.538 (3)C14—C151.536 (3)
C8—C141.526 (3)C15—C161.534 (3)
C8—C91.550 (3)C16—C171.507 (3)
C9—O111.453 (2)C17—O171.217 (3)
C2—C1—C10112.84 (19)C1—C10—C9111.87 (16)
C3—C2—C1110.61 (18)C5—C10—C9111.14 (15)
O3—C3—C4108.06 (18)C19—C10—C9105.80 (16)
O3—C3—C2112.61 (18)O11—C11—C959.26 (12)
C4—C3—C2111.47 (17)O11—C11—C12115.29 (17)
C3—C4—C5112.98 (17)C9—C11—C12124.93 (18)
C6—C5—C4112.62 (17)C11—O11—C962.23 (12)
C6—C5—C10111.43 (16)C11—C12—C13111.98 (16)
C4—C5—C10112.71 (16)C12—C13—C17115.59 (16)
C7—C6—C5109.62 (17)C12—C13—C14107.84 (16)
C6—C7—C8115.27 (17)C17—C13—C14100.74 (15)
C14—C8—C7106.71 (16)C12—C13—C18113.25 (17)
C14—C8—C9110.76 (15)C17—C13—C18104.10 (16)
C7—C8—C9113.59 (16)C14—C13—C18114.84 (16)
O11—C9—C1158.51 (12)C8—C14—C13117.10 (15)
O11—C9—C10110.02 (15)C8—C14—C15118.66 (16)
C11—C9—C10122.83 (16)C13—C14—C15104.33 (16)
O11—C9—C8113.72 (14)C16—C15—C14101.98 (16)
C11—C9—C8117.95 (17)C17—C16—C15105.59 (17)
C10—C9—C8117.16 (16)O17—C17—C16125.0 (2)
C1—C10—C5107.49 (15)O17—C17—C13125.84 (19)
C1—C10—C19109.40 (18)C16—C17—C13109.16 (17)
C5—C10—C19111.16 (17)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3A···O17i0.822.022.828 (2)171
C18—H18B···O110.962.322.990 (3)126
Symmetry code: (i) x1/2, y+2, z1/2.

Experimental details

Crystal data
Chemical formulaC19H28O3
Mr304.41
Crystal system, space groupOrthorhombic, P212121
Temperature (K)293
a, b, c (Å)7.3171 (3), 10.6462 (6), 21.0401 (14)
V3)1639.01 (16)
Z4
Radiation typeCu Kα
µ (mm1)0.64
Crystal size (mm)0.64 × 0.46 × 0.28
Data collection
DiffractometerSiemens P4 four-circle
diffractometer
Absorption correctionψ scan
(North et al., 1968)
Tmin, Tmax0.615, 0.835
No. of measured, independent and
observed [I > 2σ(I)] reflections
2214, 2031, 1987
Rint0.043
(sin θ/λ)max1)0.606
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.036, 0.103, 1.07
No. of reflections2031
No. of parameters203
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.21, 0.16
Absolute structureFlack (1983); 388 Friedel pairs
Absolute structure parameter0.3 (3)

Computer programs: XSCANS (Siemens, 1996), XSCANS, SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 1997), DIAMOND (Bergerhoff, 1996), PLATON (Spek, 1990), PARST (Nardelli, 1983, 1995) and PARSTCIF (Nardelli, 1991).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3A···O17i0.822.022.828 (2)171
C18—H18B···O110.962.322.990 (3)126
Symmetry code: (i) x1/2, y+2, z1/2.
 

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