Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536800018845/cf6010sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536800018845/cf6010Isup2.hkl |
CCDC reference: 155880
The synthesis of the title compound is described by Ruíz (1997). Crystals (m.p. 529 K) were grown by slow evaporation from ethanol.
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.
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).
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. |
C19H28O3 | Dx = 1.234 Mg m−3 |
Mr = 304.41 | Melting point: 236 K |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54180 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 40 reflections |
a = 7.3171 (3) Å | θ = 10.5–28.0° |
b = 10.6462 (6) Å | µ = 0.64 mm−1 |
c = 21.0401 (14) Å | T = 293 K |
V = 1639.01 (16) Å3 | Prism, colourless |
Z = 4 | 0.64 × 0.46 × 0.28 mm |
F(000) = 664 |
Siemens P4 four-circle diffractometer | 1987 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.043 |
Graphite monochromator | θmax = 69.1°, θmin = 4.2° |
ω/2θ scans | h = −8→1 |
Absorption correction: ψ scan (North et al., 1968) | k = −1→12 |
Tmin = 0.615, Tmax = 0.835 | l = −1→25 |
2214 measured reflections | 3 standard reflections every 100 reflections |
2031 independent reflections | intensity decay: none |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-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 = 1.07 | Δρmax = 0.21 e Å−3 |
2031 reflections | Δρmin = −0.16 e Å−3 |
203 parameters | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
0 restraints | Extinction coefficient: 0.0148 (11) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack (1983); 388 Friedel pairs |
Secondary atom site location: difference Fourier map | Absolute structure parameter: −0.3 (3) |
C19H28O3 | V = 1639.01 (16) Å3 |
Mr = 304.41 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 7.3171 (3) Å | µ = 0.64 mm−1 |
b = 10.6462 (6) Å | T = 293 K |
c = 21.0401 (14) Å | 0.64 × 0.46 × 0.28 mm |
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 = 0.835 | 3 standard reflections every 100 reflections |
2214 measured reflections | intensity decay: none |
2031 independent reflections |
R[F2 > 2σ(F2)] = 0.036 | H-atom parameters constrained |
wR(F2) = 0.103 | Δρmax = 0.21 e Å−3 |
S = 1.07 | Δρmin = −0.16 e Å−3 |
2031 reflections | Absolute structure: Flack (1983); 388 Friedel pairs |
203 parameters | Absolute structure parameter: −0.3 (3) |
0 restraints |
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. |
x | y | z | Uiso*/Ueq | ||
C1 | −0.2916 (3) | 0.8888 (2) | 0.27104 (10) | 0.0416 (5) | |
H1A | −0.4013 | 0.8841 | 0.2968 | 0.052* | |
H1B | −0.2607 | 0.9768 | 0.2658 | 0.052* | |
C2 | −0.3310 (3) | 0.8316 (3) | 0.20555 (10) | 0.0491 (6) | |
H2A | −0.3703 | 0.7452 | 0.2106 | 0.061* | |
H2B | −0.4291 | 0.8778 | 0.1852 | 0.061* | |
C3 | −0.1616 (3) | 0.8359 (2) | 0.16399 (10) | 0.0410 (5) | |
H3 | −0.1315 | 0.9242 | 0.1560 | 0.051* | |
O3 | −0.1879 (2) | 0.77530 (19) | 0.10416 (7) | 0.0545 (5) | |
H3A | −0.2893 | 0.7929 | 0.0902 | 0.068* | |
C4 | −0.0005 (3) | 0.7754 (2) | 0.19632 (9) | 0.0403 (5) | |
H4A | 0.1075 | 0.7878 | 0.1703 | 0.050* | |
H4B | −0.0221 | 0.6857 | 0.1995 | 0.050* | |
C5 | 0.0354 (3) | 0.8281 (2) | 0.26268 (9) | 0.0339 (4) | |
H5 | 0.0646 | 0.9172 | 0.2571 | 0.042* | |
C6 | 0.2000 (3) | 0.7685 (2) | 0.29433 (10) | 0.0432 (5) | |
H6A | 0.1730 | 0.6818 | 0.3050 | 0.054* | |
H6B | 0.3031 | 0.7692 | 0.2653 | 0.054* | |
C7 | 0.2479 (3) | 0.8407 (2) | 0.35406 (10) | 0.0396 (5) | |
H7A | 0.2890 | 0.9239 | 0.3419 | 0.050* | |
H7B | 0.3495 | 0.7988 | 0.3748 | 0.050* | |
C8 | 0.0917 (3) | 0.85474 (18) | 0.40246 (9) | 0.0318 (4) | |
H8 | 0.0819 | 0.7766 | 0.4268 | 0.040* | |
C9 | −0.0962 (2) | 0.88276 (18) | 0.37157 (9) | 0.0304 (4) | |
C10 | −0.1351 (3) | 0.82229 (19) | 0.30603 (9) | 0.0316 (4) | |
C11 | −0.2053 (3) | 0.9902 (2) | 0.39730 (9) | 0.0356 (5) | |
H11 | −0.2885 | 1.0298 | 0.3668 | 0.044* | |
O11 | −0.25030 (19) | 0.86249 (14) | 0.41395 (7) | 0.0387 (4) | |
C12 | −0.1480 (3) | 1.07242 (19) | 0.45184 (10) | 0.0358 (5) | |
H12A | −0.2536 | 1.0905 | 0.4782 | 0.045* | |
H12B | −0.1022 | 1.1515 | 0.4354 | 0.045* | |
C13 | −0.0006 (3) | 1.01079 (17) | 0.49239 (9) | 0.0320 (4) | |
C14 | 0.1469 (2) | 0.96026 (18) | 0.44767 (10) | 0.0321 (4) | |
H14 | 0.1788 | 1.0312 | 0.4201 | 0.040* | |
C15 | 0.3143 (3) | 0.9410 (2) | 0.49062 (11) | 0.0432 (5) | |
H15A | 0.3026 | 0.8655 | 0.5160 | 0.054* | |
H15B | 0.4261 | 0.9366 | 0.4660 | 0.054* | |
C16 | 0.3094 (3) | 1.0593 (2) | 0.53220 (12) | 0.0472 (5) | |
H16A | 0.3524 | 1.0407 | 0.5748 | 0.059* | |
H16B | 0.3857 | 1.1247 | 0.5141 | 0.059* | |
C17 | 0.1121 (3) | 1.09998 (19) | 0.53352 (10) | 0.0362 (5) | |
O17 | 0.0528 (2) | 1.18838 (14) | 0.56381 (8) | 0.0472 (4) | |
C18 | −0.0771 (3) | 0.9139 (2) | 0.54002 (10) | 0.0416 (5) | |
H18A | 0.0220 | 0.8763 | 0.5631 | 0.052* | |
H18B | −0.1427 | 0.8499 | 0.5174 | 0.052* | |
H18C | −0.1581 | 0.9552 | 0.5692 | 0.052* | |
C19 | −0.1905 (4) | 0.6848 (2) | 0.31999 (11) | 0.0484 (6) | |
H19A | −0.3102 | 0.6833 | 0.3387 | 0.061* | |
H19B | −0.1042 | 0.6481 | 0.3489 | 0.061* | |
H19C | −0.1914 | 0.6378 | 0.2811 | 0.061* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0309 (10) | 0.0589 (13) | 0.0349 (10) | 0.0070 (10) | −0.0005 (9) | −0.0052 (11) |
C2 | 0.0354 (11) | 0.0732 (16) | 0.0385 (11) | 0.0060 (12) | −0.0012 (9) | −0.0063 (13) |
C3 | 0.0449 (12) | 0.0477 (11) | 0.0303 (10) | 0.0033 (11) | 0.0005 (9) | −0.0037 (10) |
O3 | 0.0518 (9) | 0.0773 (12) | 0.0346 (8) | 0.0139 (10) | −0.0060 (7) | −0.0139 (9) |
C4 | 0.0387 (10) | 0.0493 (11) | 0.0330 (10) | 0.0039 (10) | 0.0035 (9) | −0.0013 (10) |
C5 | 0.0325 (10) | 0.0382 (9) | 0.0309 (10) | 0.0022 (9) | 0.0058 (8) | 0.0009 (9) |
C6 | 0.0367 (11) | 0.0546 (13) | 0.0382 (10) | 0.0129 (11) | 0.0048 (9) | −0.0058 (11) |
C7 | 0.0308 (9) | 0.0510 (12) | 0.0371 (10) | 0.0102 (10) | 0.0006 (8) | −0.0020 (11) |
C8 | 0.0332 (9) | 0.0310 (9) | 0.0312 (9) | 0.0047 (8) | −0.0007 (8) | 0.0008 (9) |
C9 | 0.0282 (9) | 0.0339 (9) | 0.0291 (9) | 0.0010 (8) | 0.0029 (8) | 0.0026 (9) |
C10 | 0.0295 (9) | 0.0350 (9) | 0.0303 (9) | −0.0014 (8) | 0.0037 (7) | −0.0013 (9) |
C11 | 0.0326 (9) | 0.0415 (10) | 0.0327 (9) | 0.0054 (9) | 0.0016 (8) | 0.0003 (9) |
O11 | 0.0363 (7) | 0.0450 (8) | 0.0349 (7) | −0.0050 (7) | 0.0099 (6) | −0.0035 (7) |
C12 | 0.0360 (9) | 0.0363 (9) | 0.0352 (10) | 0.0067 (9) | 0.0033 (8) | −0.0018 (9) |
C13 | 0.0345 (9) | 0.0291 (8) | 0.0325 (10) | −0.0027 (8) | 0.0033 (8) | −0.0018 (9) |
C14 | 0.0316 (9) | 0.0304 (8) | 0.0343 (10) | 0.0023 (8) | 0.0026 (8) | 0.0028 (9) |
C15 | 0.0369 (10) | 0.0421 (11) | 0.0506 (12) | 0.0055 (9) | −0.0085 (10) | −0.0094 (11) |
C16 | 0.0429 (11) | 0.0440 (11) | 0.0547 (13) | −0.0006 (10) | −0.0080 (11) | −0.0115 (12) |
C17 | 0.0430 (10) | 0.0327 (9) | 0.0328 (10) | −0.0059 (9) | 0.0032 (8) | 0.0010 (10) |
O17 | 0.0498 (9) | 0.0435 (8) | 0.0482 (8) | −0.0046 (7) | 0.0095 (7) | −0.0146 (8) |
C18 | 0.0523 (11) | 0.0409 (10) | 0.0317 (9) | −0.0104 (11) | 0.0034 (9) | 0.0029 (10) |
C19 | 0.0640 (14) | 0.0413 (11) | 0.0400 (11) | −0.0140 (12) | 0.0078 (12) | −0.0019 (11) |
C1—C2 | 1.534 (3) | C9—C11 | 1.496 (3) |
C1—C10 | 1.534 (3) | C9—C10 | 1.548 (3) |
C2—C3 | 1.517 (3) | C10—C19 | 1.547 (3) |
C3—O3 | 1.428 (3) | C11—O11 | 1.442 (3) |
C3—C4 | 1.506 (3) | C11—C12 | 1.503 (3) |
C4—C5 | 1.527 (3) | C12—C13 | 1.524 (3) |
C5—C6 | 1.516 (3) | C13—C17 | 1.526 (3) |
C5—C10 | 1.546 (2) | C13—C14 | 1.530 (3) |
C6—C7 | 1.514 (3) | C13—C18 | 1.543 (3) |
C7—C8 | 1.538 (3) | C14—C15 | 1.536 (3) |
C8—C14 | 1.526 (3) | C15—C16 | 1.534 (3) |
C8—C9 | 1.550 (3) | C16—C17 | 1.507 (3) |
C9—O11 | 1.453 (2) | C17—O17 | 1.217 (3) |
C2—C1—C10 | 112.84 (19) | C1—C10—C9 | 111.87 (16) |
C3—C2—C1 | 110.61 (18) | C5—C10—C9 | 111.14 (15) |
O3—C3—C4 | 108.06 (18) | C19—C10—C9 | 105.80 (16) |
O3—C3—C2 | 112.61 (18) | O11—C11—C9 | 59.26 (12) |
C4—C3—C2 | 111.47 (17) | O11—C11—C12 | 115.29 (17) |
C3—C4—C5 | 112.98 (17) | C9—C11—C12 | 124.93 (18) |
C6—C5—C4 | 112.62 (17) | C11—O11—C9 | 62.23 (12) |
C6—C5—C10 | 111.43 (16) | C11—C12—C13 | 111.98 (16) |
C4—C5—C10 | 112.71 (16) | C12—C13—C17 | 115.59 (16) |
C7—C6—C5 | 109.62 (17) | C12—C13—C14 | 107.84 (16) |
C6—C7—C8 | 115.27 (17) | C17—C13—C14 | 100.74 (15) |
C14—C8—C7 | 106.71 (16) | C12—C13—C18 | 113.25 (17) |
C14—C8—C9 | 110.76 (15) | C17—C13—C18 | 104.10 (16) |
C7—C8—C9 | 113.59 (16) | C14—C13—C18 | 114.84 (16) |
O11—C9—C11 | 58.51 (12) | C8—C14—C13 | 117.10 (15) |
O11—C9—C10 | 110.02 (15) | C8—C14—C15 | 118.66 (16) |
C11—C9—C10 | 122.83 (16) | C13—C14—C15 | 104.33 (16) |
O11—C9—C8 | 113.72 (14) | C16—C15—C14 | 101.98 (16) |
C11—C9—C8 | 117.95 (17) | C17—C16—C15 | 105.59 (17) |
C10—C9—C8 | 117.16 (16) | O17—C17—C16 | 125.0 (2) |
C1—C10—C5 | 107.49 (15) | O17—C17—C13 | 125.84 (19) |
C1—C10—C19 | 109.40 (18) | C16—C17—C13 | 109.16 (17) |
C5—C10—C19 | 111.16 (17) |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3A···O17i | 0.82 | 2.02 | 2.828 (2) | 171 |
C18—H18B···O11 | 0.96 | 2.32 | 2.990 (3) | 126 |
Symmetry code: (i) −x−1/2, −y+2, z−1/2. |
Experimental details
Crystal data | |
Chemical formula | C19H28O3 |
Mr | 304.41 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 293 |
a, b, c (Å) | 7.3171 (3), 10.6462 (6), 21.0401 (14) |
V (Å3) | 1639.01 (16) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.64 |
Crystal size (mm) | 0.64 × 0.46 × 0.28 |
Data collection | |
Diffractometer | Siemens P4 four-circle diffractometer |
Absorption correction | ψ scan (North et al., 1968) |
Tmin, Tmax | 0.615, 0.835 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2214, 2031, 1987 |
Rint | 0.043 |
(sin θ/λ)max (Å−1) | 0.606 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.036, 0.103, 1.07 |
No. of reflections | 2031 |
No. of parameters | 203 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.21, −0.16 |
Absolute structure | Flack (1983); 388 Friedel pairs |
Absolute structure parameter | −0.3 (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).
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3A···O17i | 0.82 | 2.02 | 2.828 (2) | 171 |
C18—H18B···O11 | 0.96 | 2.32 | 2.990 (3) | 126 |
Symmetry code: (i) −x−1/2, −y+2, z−1/2. |
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).