Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270109010233/sk3302sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270109010233/sk3302Isup2.hkl |
CCDC reference: 735124
The synthesis of 6β-hydroxy-5β-methyl-20-oxo-19-norpregn-9(10)-en-3β-yl acetate, (I), was efficiently accomplished according to the previously reported method of Pinto, Salvador, Le Roux et al. (2008). The product of this reaction was isolated in 52% yield and identified as (I) from MS, IR, one-dimensional and two-dimensional NMR (Pinto, Salvador, Le Roux et al., 2008). Recrystallization from acetone/n-hexane at room temperature gave colourless single crystals suitable for X-ray diffraction analysis.
All H atoms were refined as riding on their parent atoms using SHELXL97 defaults, except for that of the hydroxyl group which had its coordinates freely refined with Uiso(H) = 1.5Ueq(O). The absolute configuration was not determined from the X-ray data but was known from the synthetic route.
Data collection: SMART (Bruker, 2003); cell refinement: SAINT (Bruker, 2003); data reduction: SAINT (Bruker, 2003); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).
Fig. 1. View of the molecule of the title compound, with displacement ellipsoids drawn at the 50% probability level. |
C23H34O4 | Dx = 1.178 Mg m−3 |
Mr = 374.50 | Melting point: 411 K |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 6566 reflections |
a = 5.8903 (2) Å | θ = 2.4–26.3° |
b = 9.6929 (2) Å | µ = 0.08 mm−1 |
c = 36.9988 (8) Å | T = 293 K |
V = 2112.41 (10) Å3 | Flat hexagonal prism, clear colourless |
Z = 4 | 0.36 × 0.23 × 0.11 mm |
F(000) = 816 |
Bruker APEXII CCD area-detector diffractometer | 3729 independent reflections |
Radiation source: fine-focus sealed tube | 2885 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.041 |
ϕ and ω scans | θmax = 30.5°, θmin = 2.2° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2000) | h = −8→8 |
Tmin = 0.882, Tmax = 0.991 | k = −13→13 |
59317 measured reflections | l = −52→52 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.044 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.133 | H-atom parameters constrained |
S = 1.05 | w = 1/[σ2(Fo2) + (0.0779P)2 + 0.1174P] where P = (Fo2 + 2Fc2)/3 |
3729 reflections | (Δ/σ)max < 0.001 |
249 parameters | Δρmax = 0.18 e Å−3 |
0 restraints | Δρmin = −0.17 e Å−3 |
C23H34O4 | V = 2112.41 (10) Å3 |
Mr = 374.50 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 5.8903 (2) Å | µ = 0.08 mm−1 |
b = 9.6929 (2) Å | T = 293 K |
c = 36.9988 (8) Å | 0.36 × 0.23 × 0.11 mm |
Bruker APEXII CCD area-detector diffractometer | 3729 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2000) | 2885 reflections with I > 2σ(I) |
Tmin = 0.882, Tmax = 0.991 | Rint = 0.041 |
59317 measured reflections |
R[F2 > 2σ(F2)] = 0.044 | 0 restraints |
wR(F2) = 0.133 | H-atom parameters constrained |
S = 1.05 | Δρmax = 0.18 e Å−3 |
3729 reflections | Δρmin = −0.17 e Å−3 |
249 parameters |
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 | 0.4722 (4) | 0.12481 (19) | 0.12583 (5) | 0.0490 (5) | |
H1A | 0.5308 | 0.1163 | 0.1502 | 0.059* | |
H1B | 0.5598 | 0.0636 | 0.1105 | 0.059* | |
C2 | 0.2256 (4) | 0.0786 (2) | 0.12548 (5) | 0.0525 (5) | |
H2A | 0.2163 | −0.0171 | 0.1330 | 0.063* | |
H2B | 0.1391 | 0.1337 | 0.1425 | 0.063* | |
C3 | 0.1252 (4) | 0.0935 (2) | 0.08821 (5) | 0.0489 (4) | |
H3 | −0.0358 | 0.0680 | 0.0887 | 0.059* | |
O3A | 0.2516 (3) | −0.00496 (14) | 0.06584 (4) | 0.0515 (3) | |
C3A | 0.1608 (4) | −0.0463 (2) | 0.03472 (5) | 0.0527 (5) | |
O3B | −0.0239 (3) | −0.0109 (2) | 0.02454 (4) | 0.0742 (5) | |
C3B | 0.3192 (5) | −0.1385 (2) | 0.01506 (6) | 0.0689 (7) | |
H3B1 | 0.3134 | −0.2292 | 0.0254 | 0.103* | |
H3B2 | 0.4708 | −0.1029 | 0.0169 | 0.103* | |
H3B3 | 0.2758 | −0.1432 | −0.0099 | 0.103* | |
C4 | 0.1503 (3) | 0.2403 (2) | 0.07486 (5) | 0.0462 (4) | |
H4A | 0.0467 | 0.2979 | 0.0886 | 0.055* | |
H4B | 0.1014 | 0.2431 | 0.0498 | 0.055* | |
C5 | 0.3888 (3) | 0.30562 (18) | 0.07705 (4) | 0.0402 (4) | |
C5A | 0.5356 (3) | 0.2532 (2) | 0.04534 (4) | 0.0476 (4) | |
H5A1 | 0.4563 | 0.2678 | 0.0230 | 0.071* | |
H5A2 | 0.5650 | 0.1565 | 0.0484 | 0.071* | |
H5A3 | 0.6767 | 0.3026 | 0.0449 | 0.071* | |
C6 | 0.3567 (4) | 0.4633 (2) | 0.07496 (4) | 0.0443 (4) | |
H6 | 0.2593 | 0.4887 | 0.0954 | 0.053* | |
O6 | 0.2385 (3) | 0.50490 (16) | 0.04296 (3) | 0.0568 (4) | |
H6A | 0.3248 | 0.5008 | 0.0256 | 0.085* | |
C7 | 0.5771 (4) | 0.5393 (2) | 0.08019 (5) | 0.0499 (5) | |
H7A | 0.5502 | 0.6377 | 0.0780 | 0.060* | |
H7B | 0.6828 | 0.5126 | 0.0614 | 0.060* | |
C8 | 0.6829 (3) | 0.50866 (19) | 0.11734 (4) | 0.0417 (4) | |
H8 | 0.8477 | 0.5173 | 0.1146 | 0.050* | |
C9 | 0.6366 (3) | 0.36341 (18) | 0.13065 (4) | 0.0409 (4) | |
C10 | 0.5061 (3) | 0.27213 (18) | 0.11307 (4) | 0.0412 (4) | |
C11 | 0.7514 (4) | 0.3358 (2) | 0.16667 (5) | 0.0503 (5) | |
H11A | 0.9147 | 0.3379 | 0.1634 | 0.060* | |
H11B | 0.7102 | 0.2442 | 0.1749 | 0.060* | |
C12 | 0.6851 (4) | 0.44162 (18) | 0.19574 (5) | 0.0453 (4) | |
H12A | 0.5245 | 0.4332 | 0.2011 | 0.054* | |
H12B | 0.7690 | 0.4230 | 0.2178 | 0.054* | |
C13 | 0.7360 (3) | 0.58741 (19) | 0.18293 (4) | 0.0397 (4) | |
C14 | 0.6117 (3) | 0.61062 (17) | 0.14663 (4) | 0.0384 (3) | |
H14 | 0.4508 | 0.5924 | 0.1514 | 0.046* | |
C15 | 0.6307 (5) | 0.7650 (2) | 0.14027 (5) | 0.0604 (6) | |
H15A | 0.5101 | 0.7974 | 0.1246 | 0.073* | |
H15B | 0.7760 | 0.7883 | 0.1295 | 0.073* | |
C16 | 0.6084 (6) | 0.8276 (2) | 0.17831 (6) | 0.0710 (7) | |
H16A | 0.4628 | 0.8732 | 0.1809 | 0.085* | |
H16B | 0.7277 | 0.8947 | 0.1825 | 0.085* | |
C17 | 0.6286 (4) | 0.7076 (2) | 0.20541 (5) | 0.0492 (4) | |
H17 | 0.4743 | 0.6795 | 0.2120 | 0.059* | |
C18 | 0.9926 (4) | 0.6111 (3) | 0.18014 (7) | 0.0648 (6) | |
H18A | 1.0619 | 0.5940 | 0.2032 | 0.097* | |
H18B | 1.0211 | 0.7048 | 0.1730 | 0.097* | |
H18C | 1.0555 | 0.5495 | 0.1625 | 0.097* | |
C20 | 0.7519 (5) | 0.7448 (3) | 0.23992 (6) | 0.0668 (6) | |
O20 | 0.8547 (6) | 0.8505 (2) | 0.24285 (6) | 0.1158 (10) | |
C21 | 0.7429 (7) | 0.6458 (3) | 0.27057 (6) | 0.0921 (11) | |
H21A | 0.8692 | 0.5834 | 0.2690 | 0.138* | |
H21B | 0.6037 | 0.5944 | 0.2695 | 0.138* | |
H21C | 0.7501 | 0.6955 | 0.2930 | 0.138* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0626 (12) | 0.0410 (9) | 0.0433 (8) | 0.0061 (9) | −0.0129 (9) | −0.0002 (8) |
C2 | 0.0628 (12) | 0.0486 (10) | 0.0462 (9) | 0.0035 (10) | 0.0044 (9) | 0.0007 (8) |
C3 | 0.0395 (9) | 0.0570 (11) | 0.0502 (9) | 0.0048 (9) | −0.0001 (8) | −0.0065 (8) |
O3A | 0.0494 (7) | 0.0536 (7) | 0.0516 (7) | 0.0060 (7) | −0.0065 (6) | −0.0118 (6) |
C3A | 0.0621 (13) | 0.0501 (10) | 0.0457 (9) | −0.0041 (10) | −0.0046 (9) | −0.0001 (8) |
O3B | 0.0676 (11) | 0.0944 (13) | 0.0605 (9) | 0.0082 (11) | −0.0198 (8) | −0.0072 (9) |
C3B | 0.0915 (19) | 0.0569 (12) | 0.0583 (11) | 0.0061 (13) | −0.0018 (13) | −0.0095 (10) |
C4 | 0.0378 (9) | 0.0558 (10) | 0.0450 (8) | 0.0128 (9) | −0.0026 (8) | −0.0034 (8) |
C5 | 0.0416 (9) | 0.0471 (9) | 0.0318 (7) | 0.0124 (8) | −0.0028 (7) | −0.0031 (7) |
C5A | 0.0426 (10) | 0.0597 (11) | 0.0406 (8) | 0.0121 (9) | 0.0005 (7) | −0.0080 (8) |
C6 | 0.0528 (11) | 0.0494 (9) | 0.0308 (7) | 0.0165 (9) | −0.0023 (8) | 0.0037 (7) |
O6 | 0.0662 (9) | 0.0660 (9) | 0.0383 (6) | 0.0236 (9) | −0.0079 (6) | 0.0083 (6) |
C7 | 0.0660 (13) | 0.0475 (9) | 0.0362 (8) | 0.0050 (10) | 0.0003 (8) | 0.0054 (7) |
C8 | 0.0429 (9) | 0.0447 (9) | 0.0377 (7) | 0.0037 (8) | 0.0006 (7) | 0.0004 (7) |
C9 | 0.0457 (9) | 0.0413 (8) | 0.0356 (7) | 0.0127 (8) | −0.0053 (7) | −0.0002 (6) |
C10 | 0.0473 (10) | 0.0411 (8) | 0.0351 (7) | 0.0107 (8) | −0.0047 (7) | −0.0005 (7) |
C11 | 0.0616 (12) | 0.0435 (9) | 0.0458 (9) | 0.0106 (10) | −0.0189 (9) | −0.0019 (8) |
C12 | 0.0552 (11) | 0.0440 (9) | 0.0366 (7) | 0.0028 (9) | −0.0109 (8) | 0.0012 (7) |
C13 | 0.0336 (8) | 0.0443 (9) | 0.0412 (8) | −0.0011 (8) | −0.0046 (7) | −0.0032 (7) |
C14 | 0.0388 (9) | 0.0379 (8) | 0.0385 (7) | 0.0026 (8) | −0.0014 (7) | 0.0001 (7) |
C15 | 0.0906 (17) | 0.0416 (9) | 0.0492 (10) | 0.0010 (12) | −0.0061 (11) | 0.0034 (8) |
C16 | 0.110 (2) | 0.0468 (11) | 0.0559 (11) | 0.0095 (14) | −0.0147 (14) | −0.0062 (9) |
C17 | 0.0550 (11) | 0.0472 (10) | 0.0454 (9) | 0.0023 (10) | −0.0052 (8) | −0.0077 (8) |
C18 | 0.0389 (10) | 0.0845 (17) | 0.0709 (13) | −0.0071 (12) | −0.0037 (10) | −0.0076 (13) |
C20 | 0.0866 (17) | 0.0616 (12) | 0.0522 (11) | −0.0017 (14) | −0.0102 (12) | −0.0142 (10) |
O20 | 0.163 (3) | 0.0923 (14) | 0.0918 (14) | −0.0498 (18) | −0.0469 (15) | −0.0115 (12) |
C21 | 0.145 (3) | 0.0878 (19) | 0.0437 (11) | 0.007 (2) | −0.0139 (16) | −0.0065 (11) |
C1—C10 | 1.517 (3) | C8—C9 | 1.516 (3) |
C1—C2 | 1.520 (3) | C8—C14 | 1.525 (2) |
C1—H1A | 0.9700 | C8—H8 | 0.9800 |
C1—H1B | 0.9700 | C9—C10 | 1.341 (3) |
C2—C3 | 1.507 (3) | C9—C11 | 1.518 (2) |
C2—H2A | 0.9700 | C11—C12 | 1.536 (3) |
C2—H2B | 0.9700 | C11—H11A | 0.9700 |
C3—O3A | 1.467 (2) | C11—H11B | 0.9700 |
C3—C4 | 1.513 (3) | C12—C13 | 1.520 (3) |
C3—H3 | 0.9800 | C12—H12A | 0.9700 |
O3A—C3A | 1.331 (2) | C12—H12B | 0.9700 |
C3A—O3B | 1.201 (3) | C13—C18 | 1.532 (3) |
C3A—C3B | 1.483 (3) | C13—C14 | 1.546 (2) |
C3B—H3B1 | 0.9600 | C13—C17 | 1.565 (3) |
C3B—H3B2 | 0.9600 | C14—C15 | 1.519 (3) |
C3B—H3B3 | 0.9600 | C14—H14 | 0.9800 |
C4—C5 | 1.543 (3) | C15—C16 | 1.538 (3) |
C4—H4A | 0.9700 | C15—H15A | 0.9700 |
C4—H4B | 0.9700 | C15—H15B | 0.9700 |
C5—C10 | 1.536 (2) | C16—C17 | 1.540 (3) |
C5—C6 | 1.542 (3) | C16—H16A | 0.9700 |
C5—C5A | 1.543 (2) | C16—H16B | 0.9700 |
C5A—H5A1 | 0.9600 | C17—C20 | 1.513 (3) |
C5A—H5A2 | 0.9600 | C17—H17 | 0.9800 |
C5A—H5A3 | 0.9600 | C18—H18A | 0.9600 |
C6—O6 | 1.432 (2) | C18—H18B | 0.9600 |
C6—C7 | 1.506 (3) | C18—H18C | 0.9600 |
C6—H6 | 0.9800 | C20—O20 | 1.195 (3) |
O6—H6A | 0.8200 | C20—C21 | 1.487 (4) |
C7—C8 | 1.538 (2) | C21—H21A | 0.9600 |
C7—H7A | 0.9700 | C21—H21B | 0.9600 |
C7—H7B | 0.9700 | C21—H21C | 0.9600 |
C10—C1—C2 | 113.60 (17) | C7—C8—H8 | 106.9 |
C10—C1—H1A | 108.8 | C10—C9—C8 | 123.94 (15) |
C2—C1—H1A | 108.8 | C10—C9—C11 | 124.41 (17) |
C10—C1—H1B | 108.8 | C8—C9—C11 | 111.64 (16) |
C2—C1—H1B | 108.8 | C9—C10—C1 | 123.06 (15) |
H1A—C1—H1B | 107.7 | C9—C10—C5 | 122.66 (16) |
C3—C2—C1 | 110.77 (17) | C1—C10—C5 | 114.20 (16) |
C3—C2—H2A | 109.5 | C9—C11—C12 | 112.56 (15) |
C1—C2—H2A | 109.5 | C9—C11—H11A | 109.1 |
C3—C2—H2B | 109.5 | C12—C11—H11A | 109.1 |
C1—C2—H2B | 109.5 | C9—C11—H11B | 109.1 |
H2A—C2—H2B | 108.1 | C12—C11—H11B | 109.1 |
O3A—C3—C2 | 104.73 (16) | H11A—C11—H11B | 107.8 |
O3A—C3—C4 | 112.22 (16) | C13—C12—C11 | 110.63 (15) |
C2—C3—C4 | 110.54 (17) | C13—C12—H12A | 109.5 |
O3A—C3—H3 | 109.8 | C11—C12—H12A | 109.5 |
C2—C3—H3 | 109.8 | C13—C12—H12B | 109.5 |
C4—C3—H3 | 109.8 | C11—C12—H12B | 109.5 |
C3A—O3A—C3 | 118.69 (17) | H12A—C12—H12B | 108.1 |
O3B—C3A—O3A | 123.3 (2) | C12—C13—C18 | 110.81 (19) |
O3B—C3A—C3B | 126.0 (2) | C12—C13—C14 | 108.20 (14) |
O3A—C3A—C3B | 110.7 (2) | C18—C13—C14 | 112.74 (17) |
C3A—C3B—H3B1 | 109.5 | C12—C13—C17 | 116.53 (16) |
C3A—C3B—H3B2 | 109.5 | C18—C13—C17 | 108.85 (18) |
H3B1—C3B—H3B2 | 109.5 | C14—C13—C17 | 99.30 (14) |
C3A—C3B—H3B3 | 109.5 | C15—C14—C8 | 120.53 (16) |
H3B1—C3B—H3B3 | 109.5 | C15—C14—C13 | 104.06 (15) |
H3B2—C3B—H3B3 | 109.5 | C8—C14—C13 | 113.12 (14) |
C3—C4—C5 | 117.24 (16) | C15—C14—H14 | 106.0 |
C3—C4—H4A | 108.0 | C8—C14—H14 | 106.0 |
C5—C4—H4A | 108.0 | C13—C14—H14 | 106.0 |
C3—C4—H4B | 108.0 | C14—C15—C16 | 103.91 (16) |
C5—C4—H4B | 108.0 | C14—C15—H15A | 111.0 |
H4A—C4—H4B | 107.2 | C16—C15—H15A | 111.0 |
C10—C5—C6 | 107.94 (14) | C14—C15—H15B | 111.0 |
C10—C5—C4 | 111.61 (15) | C16—C15—H15B | 111.0 |
C6—C5—C4 | 107.01 (15) | H15A—C15—H15B | 109.0 |
C10—C5—C5A | 109.75 (14) | C15—C16—C17 | 106.95 (17) |
C6—C5—C5A | 110.92 (16) | C15—C16—H16A | 110.3 |
C4—C5—C5A | 109.58 (14) | C17—C16—H16A | 110.3 |
C5—C5A—H5A1 | 109.5 | C15—C16—H16B | 110.3 |
C5—C5A—H5A2 | 109.5 | C17—C16—H16B | 110.3 |
H5A1—C5A—H5A2 | 109.5 | H16A—C16—H16B | 108.6 |
C5—C5A—H5A3 | 109.5 | C20—C17—C16 | 114.02 (18) |
H5A1—C5A—H5A3 | 109.5 | C20—C17—C13 | 115.56 (18) |
H5A2—C5A—H5A3 | 109.5 | C16—C17—C13 | 104.32 (16) |
O6—C6—C7 | 112.78 (16) | C20—C17—H17 | 107.5 |
O6—C6—C5 | 112.36 (15) | C16—C17—H17 | 107.5 |
C7—C6—C5 | 111.91 (16) | C13—C17—H17 | 107.5 |
O6—C6—H6 | 106.4 | C13—C18—H18A | 109.5 |
C7—C6—H6 | 106.4 | C13—C18—H18B | 109.5 |
C5—C6—H6 | 106.4 | H18A—C18—H18B | 109.5 |
C6—O6—H6A | 109.5 | C13—C18—H18C | 109.5 |
C6—C7—C8 | 111.68 (15) | H18A—C18—H18C | 109.5 |
C6—C7—H7A | 109.3 | H18B—C18—H18C | 109.5 |
C8—C7—H7A | 109.3 | O20—C20—C21 | 120.2 (2) |
C6—C7—H7B | 109.3 | O20—C20—C17 | 121.6 (2) |
C8—C7—H7B | 109.3 | C21—C20—C17 | 118.3 (2) |
H7A—C7—H7B | 107.9 | C20—C21—H21A | 109.5 |
C9—C8—C14 | 108.75 (14) | C20—C21—H21B | 109.5 |
C9—C8—C7 | 113.39 (16) | H21A—C21—H21B | 109.5 |
C14—C8—C7 | 113.47 (15) | C20—C21—H21C | 109.5 |
C9—C8—H8 | 106.9 | H21A—C21—H21C | 109.5 |
C14—C8—H8 | 106.9 | H21B—C21—H21C | 109.5 |
C10—C1—C2—C3 | 57.1 (2) | C4—C5—C10—C1 | 40.9 (2) |
C1—C2—C3—O3A | 65.3 (2) | C5A—C5—C10—C1 | −80.7 (2) |
C1—C2—C3—C4 | −55.8 (2) | C10—C9—C11—C12 | −123.2 (2) |
C2—C3—O3A—C3A | 160.07 (17) | C8—C9—C11—C12 | 55.3 (2) |
C4—C3—O3A—C3A | −80.0 (2) | C9—C11—C12—C13 | −55.9 (2) |
C3—O3A—C3A—O3B | −2.8 (3) | C11—C12—C13—C18 | −68.3 (2) |
C3—O3A—C3A—C3B | 176.56 (18) | C11—C12—C13—C14 | 55.7 (2) |
O3A—C3—C4—C5 | −65.7 (2) | C11—C12—C13—C17 | 166.49 (17) |
C2—C3—C4—C5 | 50.8 (2) | C9—C8—C14—C15 | −177.80 (19) |
C3—C4—C5—C10 | −42.8 (2) | C7—C8—C14—C15 | −50.6 (3) |
C3—C4—C5—C6 | −160.68 (15) | C9—C8—C14—C13 | 58.2 (2) |
C3—C4—C5—C5A | 78.98 (19) | C7—C8—C14—C13 | −174.57 (15) |
C10—C5—C6—O6 | −177.28 (15) | C12—C13—C14—C15 | 168.39 (18) |
C4—C5—C6—O6 | −57.0 (2) | C18—C13—C14—C15 | −68.7 (2) |
C5A—C5—C6—O6 | 62.5 (2) | C17—C13—C14—C15 | 46.4 (2) |
C10—C5—C6—C7 | 54.64 (19) | C12—C13—C14—C8 | −59.0 (2) |
C4—C5—C6—C7 | 174.89 (14) | C18—C13—C14—C8 | 63.9 (2) |
C5A—C5—C6—C7 | −65.63 (18) | C17—C13—C14—C8 | 178.92 (16) |
O6—C6—C7—C8 | 171.59 (15) | C8—C14—C15—C16 | −164.8 (2) |
C5—C6—C7—C8 | −60.55 (19) | C13—C14—C15—C16 | −36.6 (3) |
C6—C7—C8—C9 | 33.1 (2) | C14—C15—C16—C17 | 11.7 (3) |
C6—C7—C8—C14 | −91.64 (19) | C15—C16—C17—C20 | 144.0 (2) |
C14—C8—C9—C10 | 123.64 (19) | C15—C16—C17—C13 | 17.0 (3) |
C7—C8—C9—C10 | −3.6 (3) | C12—C13—C17—C20 | 80.0 (2) |
C14—C8—C9—C11 | −54.9 (2) | C18—C13—C17—C20 | −46.1 (2) |
C7—C8—C9—C11 | 177.84 (16) | C14—C13—C17—C20 | −164.15 (18) |
C8—C9—C10—C1 | 176.61 (18) | C12—C13—C17—C16 | −153.96 (19) |
C11—C9—C10—C1 | −5.0 (3) | C18—C13—C17—C16 | 79.9 (2) |
C8—C9—C10—C5 | 0.2 (3) | C14—C13—C17—C16 | −38.1 (2) |
C11—C9—C10—C5 | 178.57 (18) | C16—C17—C20—O20 | −11.5 (4) |
C2—C1—C10—C9 | 133.5 (2) | C13—C17—C20—O20 | 109.4 (3) |
C2—C1—C10—C5 | −49.8 (2) | C16—C17—C20—C21 | 168.6 (3) |
C6—C5—C10—C9 | −25.0 (2) | C13—C17—C20—C21 | −70.5 (3) |
C4—C5—C10—C9 | −142.35 (18) | C5A—C5—C13—C18 | −0.9 (2) |
C5A—C5—C10—C9 | 96.0 (2) | C1—C10—C9—C11 | −5.0 (3) |
C6—C5—C10—C1 | 158.26 (17) |
D—H···A | D—H | H···A | D···A | D—H···A |
O6—H6A···O3Bi | 0.82 | 2.06 | 2.863 (2) | 166 |
C5A—H5A2···O3A | 0.96 | 2.50 | 3.104 (3) | 121 |
C16—H16B···O20 | 0.97 | 2.39 | 2.803 (3) | 105 |
Symmetry code: (i) x+1/2, −y+1/2, −z. |
Experimental details
Crystal data | |
Chemical formula | C23H34O4 |
Mr | 374.50 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 293 |
a, b, c (Å) | 5.8903 (2), 9.6929 (2), 36.9988 (8) |
V (Å3) | 2112.41 (10) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.08 |
Crystal size (mm) | 0.36 × 0.23 × 0.11 |
Data collection | |
Diffractometer | Bruker APEXII CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2000) |
Tmin, Tmax | 0.882, 0.991 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 59317, 3729, 2885 |
Rint | 0.041 |
(sin θ/λ)max (Å−1) | 0.715 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.044, 0.133, 1.05 |
No. of reflections | 3729 |
No. of parameters | 249 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.18, −0.17 |
Computer programs: SMART (Bruker, 2003), SAINT (Bruker, 2003), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).
C3A—O3B | 1.201 (3) | C20—C21 | 1.487 (4) |
C6—O6 | 1.432 (2) | ||
C13—C17—C20—C21 | −70.5 (3) | C5A—C5—C13—C18 | −0.9 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O6—H6A···O3Bi | 0.82 | 2.06 | 2.863 (2) | 166 |
C5A—H5A2···O3A | 0.96 | 2.50 | 3.104 (3) | 121 |
C16—H16B···O20 | 0.97 | 2.39 | 2.803 (3) | 105 |
Symmetry code: (i) x+1/2, −y+1/2, −z. |
The Westphalen rearrangement is a well known reaction in steroid chemistry for the synthesis of olefinic 19-norsteroids. This classical transformation involves migration of the 10β-methyl group to the 5β-position with the formation of 5β-methyl-Δ9(10)-19-nor derivatives (Kamernitskii et al., 1987).
As part of our current interest on the application of bismuth(III) salts to the chemistry of epoxysteroids (Pinto et al., 2006, 2007; Pinto, Salvador, Le Roux et al., 2008), we have recently reported a catalytic process for the preparation of Westphalen-type compounds (Pinto, Salvador, Le Roux et al., 2008). Several 5β-methyl-Δ9(10)-19-norsteroids from the cholestane, androstane and pregnane series were prepared by reaction of the corresponding 5β,6β-epoxysteroids in 1,4-dioxane, using a catalytic amount of bismuth trifluoromethanesulfonate (Pinto, Salvador, Le Roux et al., 2008).
Of special interest was the preparation of the title 5β-methyl-Δ9(10)-19-norsteroid, (I). This compound is a pregnane derivative with a modified skeleton, structurally related to the endogenous hormone progesterone. In the last decade, extensive synthetic work developed by Polman and Kasal led to the preparation of analogues of progesterone possessing a 5β-methyl-Δ9(10)-19-nor structure, which have shown potent abortion-inducing activity (Polman & Kasal, 1990, 1991; Kasal et al., 1998). The title compound, (I), can then be seen as an intermediate in the synthesis of this family of compounds. In this communication, we report the molecular structure (I) and compare it with that of the free molecule as given by quantum mechanical ab initio calculation.
The structure of (I) with the corresponding atomic numbering scheme is shown in Fig. 1. This steroid compound is from the pregnane series with a double bond located in ring B at C9═C10. The typical C19-methyl group is absent. The acetoxy group at C3 is axial to ring A. The 5β-methyl group on ring B is also in an axial position, whereas the hydroxyl group at C6 is equatorial. The side chain attached to ring D is equatorial.
The angle between the least-squares planes of rings A and B is 19.43 (10)°, while the angle between ring A and rings C and D is 60.37 (6)°. Rings C and D are almost coplanar, as shown by the low value of the angle between their least-squares planes of 7.53 (6)°.
Rings A and ring C have conformations close to chair, as shown by the Cremer & Pople (1975) parameters [for ring A: Q = 0.507 (2)Å, θ = 168.3 (2)° and ϕ = 242.7 (11)°; for ring C: Q = 0.5811 (19)Å, θ = 2.49 (19)° and ϕ = 274 (4)°]. Ring B has a conformation close to half-chair [Q = 0.494 (2)Å, θ = 128.1 (2)° and ϕ = 246.2 (3)°]. RingD has a twisted conformation around the C13—C14 bond, with puckering parameters q2 = 0.457 (2)Å and ϕ2 = 194.4 (3)°, and asymmetry parameters (Duax & Norton, 1975) ΔC2(16) = ΔC2(13,14) = 3.9 (3)°.
Molecules of (I) are hydrogen bonded via the hydroxyl and acetoxy groups into infinite chains running in the [100] direction. Two short intramolecular interactions are present in the molecule: (i) between the 5β-methyl group and the neighbouring O3A atom and (ii) between the C20 carbonyl O atom and one of the H atoms bound to C16.
In order to gain some insight how the crystal packing of (I) might affect the molecular geometry, we have performed a quantum chemical calculation on the equilibrium geometry of the free molecule. These calculations were performed with the computer program GAMESS (Schmidt et al., 1993). A molecular orbital Roothan Hartree–Fock method was used with an extended 6–31 G(d,p) basis set. Tight conditions for convergence of both the self-consistent field cycles and maximum density and energy gradient variations were imposed (10-5 atomic units). The program was run on the Milipeia cluster of UC–LCA (using 16 Opteron cores, 2.2 GHz runing Linux).
The ab initio calculations reproduce well the observed experimental bond length and valency angles of the molecule. All valency angles match the experimental values within 2°. Calculated and experimental bond distances agree within 0.025Å, with the exception of the following bonds: C3–O3A [calculated (calc) = 1.436Å and experimental (exp) = 1.467 (2)Å], C6–O6 [calc = 1.406Å and exp = 1.432 (2)Å] and C20–C21 [calc = 1.514Å and exp = 1.487 (4)Å].
The calculations reproduce well the small angle between the least-squares planes of rings C and D [calc = 8.3° and exp = 7.53 (6)°]. However, the calculated angles between the least-squares planes of the free molecule between rings A and B [calc = 24° and exp = 19.43 (10)°] and between ring A and rings C and D [calc = 71.4° and exp = 60.37 (6)°] differ significantly from those of the molecule in the crystal. These results might be interpreted as a result of a small induced defolding of the molecule due to crystal packing. In addition, the acetoxy side chain is almost perpendicular to ring D in the calculations, but a large tilt is observed in the crystal, as shown by the C13—C17—C20—C21 torsion angle [calc = -92.6° and exp = -70.5 (3)°].
One of the aims of the present study was to gain some insight on the structural differences between the (I) and 5β,6β-epoxy-20-oxopregnan-3β-yl acetate, the starting compound for its preparation, whose structure we have recently reported recently (Pinto, Salvador & Paixão, 2008). This 5β,6β-epoxysteroid possesses a large C19–C10···C13–C18 pseudo-torsion angle of 15.74 (17)°, which indicates a significantly twisted steroid nucleus (Pinto, Salvador & Paixão, 2008).
Interestingly, the similar C5A–C5···C13—C18 pseudo-torsion abgle for the title Westphalen-type compound is much lower, with a value of -0.94 (19)°. Calculated ab initio values also reproduce these findings [22.2° for 5β,6β-epoxy-20-oxopregnan-3β-yl acetate (Pinto, Salvador & Paixão, 2008) and 5.0° for (I)]. Thus, when the 5β,6β-epoxysteroid is converted into 5β-methyl-Δ9(10)-19-norsteroid (I), a strong relief in the twist of steroid nucleus is observed. On other hand, low values for the C19–C10···C13–C18 pseudo-torsion angle are found in the literature for several 5α,6α-epoxysteroids (Hanson, Hitchcock & Nagaratnam, 1999; Hanson, Hitchcock & Kiran, 1999; Litvinovskaya et al., 1995).
These data suggest that important steric factors, such as the above-mentioned change in the torsion of the steroid nucleus, may contribute to explain the differential reactivity observed between 5β,6β-epoxy- and 5α,6α-epoxysteroids, which do not react under the same reaction conditions (Pinto, Salvador, Le Roux et al., 2008), although similar electronic factors are present in both diastereomeric epoxides.