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The title compounds, C
22H
31NO
3 and C
20H
27NO
2, have similar conformations except in the molecular geometry and the bonding of two of the rings. These differences lead to marked differences in the biological activities of these compounds. Molecules of both compounds are linked by weak C—H
O hydrogen bonds in the crystal structures.
Supporting information
CCDC references: 251326; 251327
The preparation of (1) and (2) was described by Miljković at al. (1997). Treatment of (2) with acetic anhydride in pyridine (b) afforded the fragmentation product (I). By further treatment with sodium ethoxide in ethanol (c), compound (I) was transformed into 3β-hydroxy-17-methyl-17-oxo-16,17-seco-5-androstene-16-carbonitrile. Oppenauer oxidation of this compound using aluminium(III) tert-butoxide in cyclohexanone (d) gave (II) (Penov-Gaši et al., 2001). M.p. 398–401 K for (I) and 406–409 K for (II).
H atoms were placed in idealized positions? and treatd as riding, with Uiso(H) values fixed at 1.3Ueq of the parent atoms, or 1.5 Ueq for methyl H atoms.
For both compounds, data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software; data reduction: CAD-4 Software; program(s) used to solve structure: SHELXS86 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows, Version 1.074 (Farrugia, 1997); software used to prepare material for publication: CSU (Vicković, 1988).
(I) 3
β-acetoxy-17-methyl-17-oxo-16,17-seco-5-androstene-16-carbonitrile
top
Crystal data top
C22H31NO3 | F(000) = 776 |
Mr = 357.48 | Dx = 1.194 Mg m−3 |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54180 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 25 reflections |
a = 5.946 (2) Å | θ = 15.0–23.9° |
b = 16.120 (2) Å | µ = 0.62 mm−1 |
c = 20.746 (3) Å | T = 293 K |
V = 1988.5 (8) Å3 | Plate, colourless |
Z = 4 | 0.20 × 0.18 × 0.04 mm |
Data collection top
Enraf–Nonius CAD-4 diffractometer | Rint = 0.037 |
Radiation source: fine-focus sealed tube | θmax = 74.7°, θmin = 3.5° |
Graphite monochromator | h = −6→7 |
ω/2θ scans | k = −20→20 |
6350 measured reflections | l = −25→25 |
2354 independent reflections | 3 standard reflections every 120 min |
1621 reflections with I > 2σ(I) | intensity decay: none |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.040 | H-atom parameters constrained |
wR(F2) = 0.136 | w = 1/[σ2(Fo2) + (0.0734P)2 + 0.1452P] where P = (Fo2 + 2Fc2)/3 |
S = 0.99 | (Δ/σ)max = 0.035 |
2354 reflections | Δρmax = 0.21 e Å−3 |
240 parameters | Δρmin = −0.17 e Å−3 |
12 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0015 (4) |
Crystal data top
C22H31NO3 | V = 1988.5 (8) Å3 |
Mr = 357.48 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 5.946 (2) Å | µ = 0.62 mm−1 |
b = 16.120 (2) Å | T = 293 K |
c = 20.746 (3) Å | 0.20 × 0.18 × 0.04 mm |
Data collection top
Enraf–Nonius CAD-4 diffractometer | Rint = 0.037 |
6350 measured reflections | 3 standard reflections every 120 min |
2354 independent reflections | intensity decay: none |
1621 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.040 | 12 restraints |
wR(F2) = 0.136 | H-atom parameters constrained |
S = 0.99 | Δρmax = 0.21 e Å−3 |
2354 reflections | Δρmin = −0.17 e Å−3 |
240 parameters | |
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 | x | y | z | Uiso*/Ueq | |
C1 | −0.0163 (6) | 0.06363 (17) | 0.86123 (14) | 0.0554 (8) | |
H1A | −0.0882 | 0.0153 | 0.8424 | 0.072* | |
H1B | 0.1419 | 0.0615 | 0.8499 | 0.072* | |
C2 | −0.0379 (8) | 0.0586 (2) | 0.93461 (15) | 0.0635 (9) | |
H2A | −0.1954 | 0.0541 | 0.9463 | 0.082* | |
H2B | 0.0387 | 0.0093 | 0.9501 | 0.082* | |
C3 | 0.0619 (6) | 0.1341 (2) | 0.96606 (14) | 0.0573 (8) | |
H3 | 0.2245 | 0.1357 | 0.9584 | 0.075* | |
C4 | −0.0466 (7) | 0.2127 (2) | 0.94081 (14) | 0.0562 (8) | |
H4A | −0.2029 | 0.2143 | 0.9541 | 0.073* | |
H4B | 0.0287 | 0.2605 | 0.9592 | 0.073* | |
C5 | −0.0337 (6) | 0.21722 (17) | 0.86811 (13) | 0.0467 (7) | |
C6 | 0.0463 (6) | 0.28373 (19) | 0.83919 (15) | 0.0539 (7) | |
H6 | 0.1030 | 0.3257 | 0.8653 | 0.070* | |
C7 | 0.0538 (6) | 0.29735 (17) | 0.76779 (14) | 0.0547 (8) | |
H7A | 0.2084 | 0.2937 | 0.7532 | 0.071* | |
H7B | −0.0004 | 0.3527 | 0.7582 | 0.071* | |
C8 | −0.0883 (5) | 0.23420 (16) | 0.73111 (12) | 0.0417 (6) | |
H8 | −0.2470 | 0.2479 | 0.7380 | 0.054* | |
C9 | −0.0446 (5) | 0.14728 (16) | 0.75956 (12) | 0.0420 (6) | |
H9 | 0.1186 | 0.1390 | 0.7592 | 0.055* | |
C10 | −0.1206 (5) | 0.14242 (18) | 0.83103 (13) | 0.0436 (6) | |
C11 | −0.1461 (6) | 0.07858 (17) | 0.71803 (14) | 0.0550 (8) | |
H11A | −0.1002 | 0.0250 | 0.7348 | 0.072* | |
H11B | −0.3089 | 0.0816 | 0.7201 | 0.072* | |
C12 | −0.0703 (6) | 0.08662 (18) | 0.64824 (14) | 0.0525 (8) | |
H12A | −0.1329 | 0.0411 | 0.6234 | 0.068* | |
H12B | 0.0922 | 0.0823 | 0.6464 | 0.068* | |
C13 | −0.1431 (5) | 0.16902 (19) | 0.61770 (14) | 0.0438 (6) | |
C14 | −0.0400 (5) | 0.23978 (16) | 0.65810 (12) | 0.0423 (6) | |
H14 | 0.1233 | 0.2341 | 0.6536 | 0.055* | |
C15 | −0.0987 (6) | 0.32725 (18) | 0.63134 (14) | 0.0525 (8) | |
H15A | 0.0242 | 0.3647 | 0.6413 | 0.068* | |
H15B | −0.1101 | 0.3238 | 0.5848 | 0.068* | |
C16 | −0.3070 (7) | 0.3628 (2) | 0.65641 (16) | 0.0615 (9) | |
C17 | −0.0397 (6) | 0.1682 (2) | 0.54995 (14) | 0.0506 (7) | |
C18 | −0.4006 (5) | 0.1757 (2) | 0.61359 (18) | 0.0604 (9) | |
H18A | −0.4608 | 0.1253 | 0.5961 | 0.091* | |
H18B | −0.4406 | 0.2214 | 0.5862 | 0.091* | |
H18C | −0.4611 | 0.1847 | 0.6559 | 0.091* | |
C19 | −0.3782 (5) | 0.1382 (2) | 0.83789 (16) | 0.0621 (9) | |
H19A | −0.4314 | 0.0861 | 0.8214 | 0.093* | |
H19B | −0.4455 | 0.1827 | 0.8140 | 0.093* | |
H19C | −0.4185 | 0.1430 | 0.8825 | 0.093* | |
C20 | −0.1397 (8) | 0.1105 (2) | 0.50048 (15) | 0.0689 (10) | |
H20A | −0.3008 | 0.1130 | 0.5029 | 0.103* | |
H20B | −0.0904 | 0.0549 | 0.5088 | 0.103* | |
H20C | −0.0915 | 0.1271 | 0.4582 | 0.103* | |
C21 | 0.1570 (8) | 0.0878 (2) | 1.07213 (16) | 0.0669 (10) | |
C22 | 0.0830 (6) | 0.0871 (2) | 1.14097 (14) | 0.0755 (9) | |
H22A | −0.0631 | 0.0621 | 1.1441 | 0.113* | |
H22B | 0.0763 | 0.1430 | 1.1568 | 0.113* | |
H22C | 0.1885 | 0.0559 | 1.1662 | 0.113* | |
N | −0.4672 (7) | 0.3922 (2) | 0.67604 (17) | 0.0874 (11) | |
O1 | 0.0167 (4) | 0.13247 (15) | 1.03521 (10) | 0.0660 (7) | |
O2 | 0.3212 (7) | 0.0556 (2) | 1.05156 (14) | 0.1108 (13) | |
O3 | 0.1237 (4) | 0.20963 (15) | 0.53627 (11) | 0.0646 (6) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.066 (2) | 0.0453 (16) | 0.0547 (17) | 0.0029 (16) | −0.0003 (16) | 0.0098 (13) |
C2 | 0.077 (2) | 0.0567 (19) | 0.0568 (17) | 0.002 (2) | −0.0016 (19) | 0.0154 (15) |
C3 | 0.0612 (19) | 0.0642 (19) | 0.0466 (15) | 0.0069 (18) | 0.0023 (16) | 0.0101 (14) |
C4 | 0.066 (2) | 0.0562 (18) | 0.0468 (15) | 0.0043 (18) | −0.0012 (17) | 0.0032 (13) |
C5 | 0.0477 (16) | 0.0458 (14) | 0.0466 (14) | 0.0033 (14) | 0.0014 (14) | 0.0027 (13) |
C6 | 0.0611 (18) | 0.0501 (16) | 0.0505 (15) | −0.0094 (16) | −0.0035 (16) | −0.0021 (13) |
C7 | 0.068 (2) | 0.0449 (15) | 0.0508 (16) | −0.0156 (16) | 0.0014 (17) | 0.0008 (13) |
C8 | 0.0424 (16) | 0.0409 (13) | 0.0418 (13) | −0.0016 (12) | 0.0021 (13) | 0.0011 (11) |
C9 | 0.0399 (14) | 0.0385 (13) | 0.0475 (14) | −0.0008 (13) | 0.0002 (12) | 0.0031 (12) |
C10 | 0.0384 (14) | 0.0452 (15) | 0.0472 (15) | 0.0000 (13) | 0.0029 (13) | 0.0077 (13) |
C11 | 0.068 (2) | 0.0419 (15) | 0.0549 (17) | −0.0068 (17) | 0.0006 (17) | 0.0010 (13) |
C12 | 0.059 (2) | 0.0431 (15) | 0.0559 (17) | 0.0012 (15) | 0.0000 (15) | −0.0040 (13) |
C13 | 0.0379 (14) | 0.0457 (15) | 0.0478 (15) | −0.0015 (13) | −0.0014 (13) | −0.0008 (13) |
C14 | 0.0397 (13) | 0.0423 (14) | 0.0450 (13) | −0.0028 (13) | 0.0030 (13) | 0.0023 (12) |
C15 | 0.063 (2) | 0.0432 (15) | 0.0508 (16) | −0.0003 (15) | 0.0103 (16) | 0.0082 (13) |
C16 | 0.080 (2) | 0.0503 (17) | 0.0540 (17) | 0.0119 (19) | 0.0015 (17) | 0.0090 (15) |
C17 | 0.0477 (17) | 0.0515 (16) | 0.0525 (16) | 0.0044 (16) | −0.0004 (16) | 0.0017 (14) |
C18 | 0.0439 (18) | 0.067 (2) | 0.070 (2) | −0.0041 (16) | −0.0042 (16) | −0.0018 (17) |
C19 | 0.0429 (16) | 0.079 (2) | 0.0639 (19) | −0.0055 (18) | 0.0070 (15) | 0.0036 (19) |
C20 | 0.085 (3) | 0.066 (2) | 0.0551 (17) | −0.006 (2) | −0.0092 (19) | −0.0121 (16) |
C21 | 0.083 (3) | 0.061 (2) | 0.0572 (19) | 0.007 (2) | −0.009 (2) | 0.0110 (17) |
C22 | 0.089 (3) | 0.077 (2) | 0.0565 (19) | −0.001 (2) | −0.008 (2) | 0.0133 (17) |
N | 0.096 (3) | 0.073 (2) | 0.092 (2) | 0.033 (2) | 0.017 (2) | 0.0109 (18) |
O1 | 0.0691 (15) | 0.0801 (15) | 0.0489 (11) | 0.0117 (14) | −0.0002 (11) | 0.0144 (11) |
O2 | 0.128 (3) | 0.130 (3) | 0.0742 (18) | 0.074 (3) | −0.007 (2) | 0.0100 (17) |
O3 | 0.0553 (13) | 0.0822 (16) | 0.0565 (13) | −0.0091 (14) | 0.0087 (11) | 0.0002 (12) |
Geometric parameters (Å, º) top
C1—C2 | 1.530 (4) | C12—C13 | 1.534 (4) |
C1—C10 | 1.546 (4) | C12—H12A | 0.9700 |
C1—H1A | 0.9700 | C12—H12B | 0.9700 |
C1—H1B | 0.9700 | C13—C17 | 1.534 (4) |
C2—C3 | 1.503 (5) | C13—C18 | 1.537 (4) |
C2—H2A | 0.9700 | C13—C14 | 1.542 (4) |
C2—H2B | 0.9700 | C14—C15 | 1.555 (4) |
C3—O1 | 1.460 (4) | C14—H14 | 0.9800 |
C3—C4 | 1.516 (4) | C15—C16 | 1.460 (5) |
C3—H3 | 0.9800 | C15—H15A | 0.9700 |
C4—C5 | 1.512 (4) | C15—H15B | 0.9700 |
C4—H4A | 0.9700 | C16—N | 1.139 (5) |
C4—H4B | 0.9700 | C17—O3 | 1.213 (4) |
C5—C6 | 1.318 (4) | C17—C20 | 1.506 (4) |
C5—C10 | 1.521 (4) | C18—H18A | 0.9600 |
C6—C7 | 1.498 (4) | C18—H18B | 0.9600 |
C6—H6 | 0.9300 | C18—H18C | 0.9600 |
C7—C8 | 1.526 (4) | C19—H19A | 0.9600 |
C7—H7A | 0.9700 | C19—H19B | 0.9600 |
C7—H7B | 0.9700 | C19—H19C | 0.9600 |
C8—C9 | 1.542 (4) | C20—H20A | 0.9600 |
C8—C14 | 1.544 (4) | C20—H20B | 0.9600 |
C8—H8 | 0.9800 | C20—H20C | 0.9600 |
C9—C11 | 1.527 (4) | C21—O2 | 1.186 (5) |
C9—C10 | 1.552 (4) | C21—O1 | 1.342 (4) |
C9—H9 | 0.9800 | C21—C22 | 1.494 (5) |
C10—C19 | 1.540 (4) | C22—H22A | 0.9600 |
C11—C12 | 1.522 (4) | C22—H22B | 0.9600 |
C11—H11A | 0.9700 | C22—H22C | 0.9600 |
C11—H11B | 0.9700 | | |
| | | |
C2—C1—C10 | 114.4 (3) | C9—C11—H11B | 109.4 |
C2—C1—H1A | 108.7 | H11A—C11—H11B | 108.0 |
C10—C1—H1A | 108.7 | C11—C12—C13 | 112.5 (3) |
C2—C1—H1B | 108.7 | C11—C12—H12A | 109.1 |
C10—C1—H1B | 108.7 | C13—C12—H12A | 109.1 |
H1A—C1—H1B | 107.6 | C11—C12—H12B | 109.1 |
C3—C2—C1 | 110.8 (3) | C13—C12—H12B | 109.1 |
C3—C2—H2A | 109.5 | H12A—C12—H12B | 107.8 |
C1—C2—H2A | 109.5 | C17—C13—C18 | 110.4 (3) |
C3—C2—H2B | 109.5 | C17—C13—C12 | 104.9 (2) |
C1—C2—H2B | 109.5 | C18—C13—C12 | 111.4 (3) |
H2A—C2—H2B | 108.1 | C17—C13—C14 | 110.2 (2) |
O1—C3—C2 | 109.8 (3) | C18—C13—C14 | 112.0 (3) |
O1—C3—C4 | 106.0 (3) | C12—C13—C14 | 107.7 (2) |
C2—C3—C4 | 111.0 (3) | C8—C14—C13 | 114.6 (2) |
O1—C3—H3 | 110.0 | C8—C14—C15 | 111.2 (2) |
C2—C3—H3 | 110.0 | C13—C14—C15 | 112.8 (2) |
C4—C3—H3 | 110.0 | C8—C14—H14 | 105.8 |
C5—C4—C3 | 111.3 (3) | C13—C14—H14 | 105.8 |
C5—C4—H4A | 109.4 | C15—C14—H14 | 105.8 |
C3—C4—H4A | 109.4 | C16—C15—C14 | 114.8 (3) |
C5—C4—H4B | 109.4 | C16—C15—H15A | 108.6 |
C3—C4—H4B | 109.4 | C14—C15—H15A | 108.6 |
H4A—C4—H4B | 108.0 | C16—C15—H15B | 108.6 |
C6—C5—C4 | 120.8 (3) | C14—C15—H15B | 108.6 |
C6—C5—C10 | 122.5 (3) | H15A—C15—H15B | 107.5 |
C4—C5—C10 | 116.7 (3) | O3—C17—C20 | 119.8 (3) |
C5—C6—C7 | 125.5 (3) | O3—C17—C13 | 122.0 (3) |
C5—C6—H6 | 117.3 | C20—C17—C13 | 118.2 (3) |
C7—C6—H6 | 117.3 | C13—C18—H18A | 109.5 |
C6—C7—C8 | 112.3 (2) | C13—C18—H18B | 109.5 |
C6—C7—H7A | 109.1 | H18A—C18—H18B | 109.5 |
C8—C7—H7A | 109.2 | C13—C18—H18C | 109.5 |
C6—C7—H7B | 109.1 | H18A—C18—H18C | 109.5 |
C8—C7—H7B | 109.1 | H18B—C18—H18C | 109.5 |
H7A—C7—H7B | 107.9 | C10—C19—H19A | 109.5 |
C7—C8—C9 | 108.8 (2) | C10—C19—H19B | 109.5 |
C7—C8—C14 | 110.3 (2) | H19A—C19—H19B | 109.5 |
C9—C8—C14 | 113.4 (2) | C10—C19—H19C | 109.5 |
C7—C8—H8 | 108.1 | H19A—C19—H19C | 109.5 |
C9—C8—H8 | 108.1 | H19B—C19—H19C | 109.5 |
C14—C8—H8 | 108.1 | C17—C20—H20A | 109.5 |
C11—C9—C8 | 112.1 (2) | C17—C20—H20B | 109.5 |
C11—C9—C10 | 112.8 (2) | H20A—C20—H20B | 109.5 |
C8—C9—C10 | 111.3 (2) | C17—C20—H20C | 109.5 |
C11—C9—H9 | 106.7 | H20A—C20—H20C | 109.5 |
C8—C9—H9 | 106.7 | H20B—C20—H20C | 109.5 |
C10—C9—H9 | 106.7 | O2—C21—O1 | 122.8 (3) |
C5—C10—C19 | 109.1 (3) | O2—C21—C22 | 125.8 (4) |
C5—C10—C1 | 108.1 (2) | O1—C21—C22 | 111.4 (4) |
C19—C10—C1 | 109.0 (3) | C21—C22—H22A | 109.5 |
C5—C10—C9 | 110.1 (2) | C21—C22—H22B | 109.5 |
C19—C10—C9 | 112.3 (3) | H22A—C22—H22B | 109.5 |
C1—C10—C9 | 108.2 (2) | C21—C22—H22C | 109.5 |
C12—C11—C9 | 111.0 (2) | H22A—C22—H22C | 109.5 |
C12—C11—H11A | 109.4 | H22B—C22—H22C | 109.5 |
C9—C11—H11A | 109.4 | C21—O1—C3 | 117.1 (3) |
C12—C11—H11B | 109.4 | | |
| | | |
C10—C1—C2—C3 | −55.8 (4) | C8—C9—C10—C1 | −165.1 (3) |
C1—C2—C3—O1 | 173.5 (3) | C8—C9—C11—C12 | 52.5 (4) |
C1—C2—C3—C4 | 56.6 (4) | C10—C9—C11—C12 | 179.0 (3) |
O1—C3—C4—C5 | −173.8 (3) | C9—C11—C12—C13 | −60.8 (4) |
C2—C3—C4—C5 | −54.5 (4) | C11—C12—C13—C17 | 176.4 (3) |
C2—C1—C10—C5 | 49.6 (4) | C11—C12—C13—C18 | −64.1 (4) |
C3—C4—C5—C6 | −128.5 (3) | C11—C12—C13—C14 | 59.0 (3) |
C3—C4—C5—C10 | 52.5 (4) | C7—C8—C14—C13 | 170.0 (2) |
C4—C5—C6—C7 | −175.9 (3) | C9—C8—C14—C13 | 47.7 (3) |
C4—C5—C10—C1 | −48.5 (4) | C7—C8—C14—C15 | −60.7 (3) |
C10—C5—C6—C7 | 3.1 (6) | C9—C8—C14—C15 | 177.0 (3) |
C5—C6—C7—C8 | 12.6 (5) | C17—C13—C14—C8 | −166.2 (2) |
C6—C7—C8—C9 | −44.1 (4) | C18—C13—C14—C8 | 70.4 (3) |
C6—C7—C8—C14 | −169.1 (3) | C12—C13—C14—C8 | −52.3 (3) |
C7—C8—C9—C11 | −169.5 (3) | C17—C13—C14—C15 | 65.2 (3) |
C14—C8—C9—C11 | −46.3 (3) | C18—C13—C14—C15 | −58.1 (4) |
C7—C8—C9—C10 | 63.2 (3) | C12—C13—C14—C15 | 179.1 (3) |
C14—C8—C9—C10 | −173.7 (2) | C8—C14—C15—C16 | −41.4 (4) |
C6—C5—C10—C19 | −109.2 (4) | C13—C14—C15—C16 | 88.9 (3) |
C4—C5—C10—C19 | 69.8 (4) | C18—C13—C17—O3 | 134.9 (3) |
C6—C5—C10—C1 | 132.5 (3) | C12—C13—C17—O3 | −104.9 (3) |
C6—C5—C10—C9 | 14.5 (4) | C14—C13—C17—O3 | 10.7 (4) |
C4—C5—C10—C9 | −166.5 (3) | C18—C13—C17—C20 | −48.1 (4) |
C2—C1—C10—C19 | −68.7 (4) | C12—C13—C17—C20 | 72.0 (3) |
C2—C1—C10—C9 | 168.9 (3) | C14—C13—C17—C20 | −172.3 (3) |
C11—C9—C10—C5 | −174.2 (2) | O2—C21—O1—C3 | 5.5 (6) |
C8—C9—C10—C5 | −47.2 (3) | C22—C21—O1—C3 | −176.4 (3) |
C11—C9—C10—C19 | −52.4 (4) | C2—C3—O1—C21 | 83.4 (4) |
C8—C9—C10—C19 | 74.6 (3) | C4—C3—O1—C21 | −156.5 (3) |
C11—C9—C10—C1 | 67.9 (3) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
C20—H20B···O2i | 0.96 | 2.55 | 3.447 (5) | 155 (1) |
Symmetry code: (i) −x+1/2, −y, z−1/2. |
(II) 17-methyl-3,17-dioxo-16,17-seco-4-androstene-16-carbonitrile
top
Crystal data top
C20H27NO2 | F(000) = 680 |
Mr = 313.43 | Dx = 1.184 Mg m−3 |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54180 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 25 reflections |
a = 8.929 (2) Å | θ = 25.0–29.6° |
b = 10.022 (3) Å | µ = 0.59 mm−1 |
c = 19.651 (9) Å | T = 293 K |
V = 1758.5 (10) Å3 | Plate, colourless |
Z = 4 | 0.45 × 0.40 × 0.06 mm |
Data collection top
Enraf–Nonius CAD-4 diffractometer | Rint = 0.054 |
Radiation source: fine-focus sealed tube | θmax = 74.6°, θmin = 4.5° |
Graphite monochromator | h = −11→11 |
ω/2θ scans | k = −12→12 |
4254 measured reflections | l = −24→24 |
2073 independent reflections | 3 standard reflections every 120 min |
1723 reflections with I > 2σ(I) | intensity decay: none |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.036 | H-atom parameters constrained |
wR(F2) = 0.119 | w = 1/[σ2(Fo2) + (0.0788P)2 + 0.1175P] where P = (Fo2 + 2Fc2)/3 |
S = 0.91 | (Δ/σ)max = 0.001 |
2073 reflections | Δρmax = 0.19 e Å−3 |
212 parameters | Δρmin = −0.14 e Å−3 |
0 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0033 (7) |
Crystal data top
C20H27NO2 | V = 1758.5 (10) Å3 |
Mr = 313.43 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 8.929 (2) Å | µ = 0.59 mm−1 |
b = 10.022 (3) Å | T = 293 K |
c = 19.651 (9) Å | 0.45 × 0.40 × 0.06 mm |
Data collection top
Enraf–Nonius CAD-4 diffractometer | Rint = 0.054 |
4254 measured reflections | 3 standard reflections every 120 min |
2073 independent reflections | intensity decay: none |
1723 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.036 | 0 restraints |
wR(F2) = 0.119 | H-atom parameters constrained |
S = 0.91 | Δρmax = 0.19 e Å−3 |
2073 reflections | Δρmin = −0.14 e Å−3 |
212 parameters | |
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 | x | y | z | Uiso*/Ueq | |
C1 | −0.0812 (3) | 0.2346 (3) | 0.64725 (12) | 0.0667 (6) | |
H1A | −0.1276 | 0.1571 | 0.6680 | 0.087* | |
H1B | −0.1203 | 0.3132 | 0.6698 | 0.087* | |
C2 | −0.1252 (4) | 0.2395 (3) | 0.57196 (13) | 0.0856 (8) | |
H2A | −0.0992 | 0.1556 | 0.5504 | 0.111* | |
H2B | −0.2327 | 0.2513 | 0.5682 | 0.111* | |
C3 | −0.0476 (4) | 0.3511 (3) | 0.53601 (13) | 0.0821 (8) | |
C4 | 0.1013 (4) | 0.3845 (2) | 0.55939 (11) | 0.0714 (6) | |
H4 | 0.1547 | 0.4486 | 0.5353 | 0.093* | |
C5 | 0.1666 (3) | 0.3291 (2) | 0.61330 (10) | 0.0595 (5) | |
C6 | 0.3255 (3) | 0.3620 (3) | 0.63036 (12) | 0.0718 (7) | |
H6A | 0.3603 | 0.4332 | 0.6009 | 0.093* | |
H6B | 0.3880 | 0.2844 | 0.6224 | 0.093* | |
C7 | 0.3405 (3) | 0.4051 (2) | 0.70404 (11) | 0.0637 (5) | |
H7A | 0.2839 | 0.4865 | 0.7112 | 0.083* | |
H7B | 0.4448 | 0.4237 | 0.7140 | 0.083* | |
C8 | 0.2834 (2) | 0.29753 (18) | 0.75210 (9) | 0.0476 (4) | |
H8 | 0.3450 | 0.2175 | 0.7459 | 0.062* | |
C9 | 0.1199 (2) | 0.26172 (18) | 0.73536 (9) | 0.0448 (4) | |
H9 | 0.0607 | 0.3417 | 0.7454 | 0.058* | |
C10 | 0.0892 (2) | 0.22770 (19) | 0.65891 (9) | 0.0527 (5) | |
C11 | 0.0638 (2) | 0.1535 (2) | 0.78385 (10) | 0.0531 (5) | |
H11A | −0.0405 | 0.1342 | 0.7740 | 0.069* | |
H11B | 0.1209 | 0.0724 | 0.7766 | 0.069* | |
C12 | 0.0786 (2) | 0.1964 (2) | 0.85772 (10) | 0.0536 (5) | |
H12A | 0.0449 | 0.1242 | 0.8868 | 0.070* | |
H12B | 0.0137 | 0.2724 | 0.8657 | 0.070* | |
C13 | 0.2404 (2) | 0.2343 (2) | 0.87764 (9) | 0.0510 (4) | |
C14 | 0.2953 (2) | 0.34169 (19) | 0.82709 (10) | 0.0493 (4) | |
H14 | 0.2253 | 0.4165 | 0.8319 | 0.064* | |
C15 | 0.4515 (2) | 0.3986 (3) | 0.84610 (13) | 0.0660 (6) | |
H15A | 0.4596 | 0.4885 | 0.8282 | 0.086* | |
H15B | 0.4587 | 0.4042 | 0.8953 | 0.086* | |
C16 | 0.5777 (3) | 0.3199 (3) | 0.82072 (14) | 0.0708 (6) | |
C17 | 0.2251 (3) | 0.2965 (3) | 0.94898 (11) | 0.0647 (6) | |
C18 | 0.3404 (3) | 0.1097 (2) | 0.87870 (12) | 0.0660 (6) | |
H18A | 0.4376 | 0.1329 | 0.8959 | 0.099* | |
H18B | 0.3500 | 0.0751 | 0.8334 | 0.099* | |
H18C | 0.2960 | 0.0432 | 0.9075 | 0.099* | |
C19 | 0.1485 (3) | 0.0878 (2) | 0.63996 (12) | 0.0691 (6) | |
H19A | 0.0925 | 0.0212 | 0.6641 | 0.104* | |
H19B | 0.2524 | 0.0813 | 0.6521 | 0.104* | |
H19C | 0.1375 | 0.0740 | 0.5919 | 0.104* | |
C20 | 0.2661 (5) | 0.2190 (4) | 1.01053 (13) | 0.1002 (11) | |
H20A | 0.3701 | 0.1952 | 1.0084 | 0.150* | |
H20B | 0.2063 | 0.1395 | 1.0127 | 0.150* | |
H20C | 0.2483 | 0.2722 | 1.0504 | 0.150* | |
N | 0.6758 (3) | 0.2605 (3) | 0.79980 (15) | 0.0993 (8) | |
O1 | −0.1046 (4) | 0.4091 (3) | 0.48759 (11) | 0.1200 (9) | |
O2 | 0.1757 (3) | 0.4077 (2) | 0.95542 (10) | 0.1046 (8) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0609 (13) | 0.0730 (13) | 0.0663 (12) | −0.0055 (12) | −0.0120 (10) | −0.0069 (11) |
C2 | 0.0888 (18) | 0.0935 (18) | 0.0746 (14) | −0.0004 (16) | −0.0267 (14) | −0.0161 (14) |
C3 | 0.111 (2) | 0.0741 (15) | 0.0608 (13) | 0.0183 (16) | −0.0180 (14) | −0.0083 (11) |
C4 | 0.0961 (18) | 0.0626 (12) | 0.0556 (10) | 0.0053 (13) | 0.0015 (12) | 0.0051 (10) |
C5 | 0.0722 (13) | 0.0546 (11) | 0.0516 (10) | 0.0026 (11) | 0.0082 (10) | 0.0009 (8) |
C6 | 0.0699 (14) | 0.0768 (15) | 0.0688 (12) | −0.0093 (13) | 0.0183 (12) | 0.0162 (11) |
C7 | 0.0573 (11) | 0.0599 (12) | 0.0739 (13) | −0.0175 (11) | 0.0063 (11) | 0.0117 (10) |
C8 | 0.0421 (8) | 0.0451 (9) | 0.0556 (10) | −0.0031 (7) | 0.0035 (7) | 0.0021 (8) |
C9 | 0.0415 (8) | 0.0436 (8) | 0.0492 (9) | −0.0018 (7) | 0.0030 (7) | −0.0001 (7) |
C10 | 0.0579 (11) | 0.0493 (10) | 0.0510 (9) | −0.0012 (9) | 0.0010 (9) | −0.0020 (8) |
C11 | 0.0481 (9) | 0.0547 (10) | 0.0564 (10) | −0.0110 (9) | 0.0047 (8) | 0.0022 (8) |
C12 | 0.0487 (10) | 0.0574 (10) | 0.0546 (10) | −0.0023 (9) | 0.0085 (9) | 0.0066 (8) |
C13 | 0.0487 (9) | 0.0542 (10) | 0.0500 (9) | 0.0058 (9) | 0.0015 (8) | −0.0001 (8) |
C14 | 0.0409 (8) | 0.0459 (9) | 0.0611 (10) | −0.0007 (8) | −0.0002 (8) | −0.0034 (8) |
C15 | 0.0495 (11) | 0.0691 (12) | 0.0795 (14) | −0.0087 (11) | −0.0013 (10) | −0.0135 (11) |
C16 | 0.0449 (11) | 0.0808 (15) | 0.0867 (15) | −0.0100 (12) | −0.0043 (11) | −0.0052 (13) |
C17 | 0.0588 (12) | 0.0772 (14) | 0.0582 (11) | 0.0039 (11) | −0.0026 (10) | −0.0091 (11) |
C18 | 0.0626 (13) | 0.0619 (12) | 0.0734 (13) | 0.0143 (11) | 0.0015 (11) | 0.0086 (10) |
C19 | 0.0911 (17) | 0.0536 (11) | 0.0626 (11) | 0.0029 (13) | 0.0099 (12) | −0.0076 (10) |
C20 | 0.135 (3) | 0.111 (2) | 0.0547 (12) | −0.006 (2) | −0.0067 (16) | 0.0020 (14) |
N | 0.0518 (12) | 0.109 (2) | 0.137 (2) | 0.0030 (14) | 0.0143 (13) | −0.0068 (18) |
O1 | 0.158 (2) | 0.1163 (17) | 0.0854 (13) | 0.0125 (19) | −0.0492 (16) | 0.0143 (13) |
O2 | 0.143 (2) | 0.0963 (14) | 0.0742 (11) | 0.0417 (16) | −0.0095 (13) | −0.0290 (10) |
Geometric parameters (Å, º) top
C1—C2 | 1.532 (3) | C11—C12 | 1.520 (3) |
C1—C10 | 1.541 (3) | C11—H11A | 0.9700 |
C1—H1A | 0.9700 | C11—H11B | 0.9700 |
C1—H1B | 0.9700 | C12—C13 | 1.544 (3) |
C2—C3 | 1.493 (5) | C12—H12A | 0.9700 |
C2—H2A | 0.9700 | C12—H12B | 0.9700 |
C2—H2B | 0.9700 | C13—C18 | 1.535 (3) |
C3—O1 | 1.226 (3) | C13—C17 | 1.540 (3) |
C3—C4 | 1.446 (5) | C13—C14 | 1.544 (3) |
C4—C5 | 1.331 (3) | C14—C15 | 1.553 (3) |
C4—H4 | 0.9300 | C14—H14 | 0.9800 |
C5—C6 | 1.495 (4) | C15—C16 | 1.463 (3) |
C5—C10 | 1.521 (3) | C15—H15A | 0.9700 |
C6—C7 | 1.517 (4) | C15—H15B | 0.9700 |
C6—H6A | 0.9700 | C16—N | 1.136 (4) |
C6—H6B | 0.9700 | C17—O2 | 1.205 (3) |
C7—C8 | 1.521 (3) | C17—C20 | 1.483 (4) |
C7—H7A | 0.9700 | C18—H18A | 0.9600 |
C7—H7B | 0.9700 | C18—H18B | 0.9600 |
C8—C14 | 1.542 (3) | C18—H18C | 0.9600 |
C8—C9 | 1.539 (2) | C19—H19A | 0.9600 |
C8—H8 | 0.9800 | C19—H19B | 0.9600 |
C9—C11 | 1.528 (3) | C19—H19C | 0.9600 |
C9—C10 | 1.565 (3) | C20—H20A | 0.9600 |
C9—H9 | 0.9800 | C20—H20B | 0.9600 |
C10—C19 | 1.544 (3) | C20—H20C | 0.9600 |
| | | |
C2—C1—C10 | 113.5 (2) | C12—C11—C9 | 111.46 (17) |
C2—C1—H1A | 108.9 | C12—C11—H11A | 109.3 |
C10—C1—H1A | 108.9 | C9—C11—H11A | 109.3 |
C2—C1—H1B | 108.9 | C12—C11—H11B | 109.3 |
C10—C1—H1B | 108.9 | C9—C11—H11B | 109.3 |
H1A—C1—H1B | 107.7 | H11A—C11—H11B | 108.0 |
C3—C2—C1 | 111.3 (2) | C11—C12—C13 | 113.18 (16) |
C3—C2—H2A | 109.4 | C11—C12—H12A | 108.9 |
C1—C2—H2A | 109.4 | C13—C12—H12A | 108.9 |
C3—C2—H2B | 109.4 | C11—C12—H12B | 108.9 |
C1—C2—H2B | 109.4 | C13—C12—H12B | 108.9 |
H2A—C2—H2B | 108.0 | H12A—C12—H12B | 107.8 |
O1—C3—C4 | 121.2 (3) | C18—C13—C17 | 111.63 (17) |
O1—C3—C2 | 122.0 (3) | C18—C13—C14 | 113.04 (16) |
C4—C3—C2 | 116.7 (2) | C17—C13—C14 | 109.39 (17) |
C5—C4—C3 | 124.0 (3) | C18—C13—C12 | 110.30 (18) |
C5—C4—H4 | 118.0 | C17—C13—C12 | 104.29 (16) |
C3—C4—H4 | 118.0 | C14—C13—C12 | 107.76 (16) |
C4—C5—C6 | 120.2 (2) | C8—C14—C13 | 113.14 (15) |
C4—C5—C10 | 123.3 (2) | C8—C14—C15 | 113.38 (16) |
C6—C5—C10 | 116.50 (19) | C13—C14—C15 | 112.71 (18) |
C5—C6—C7 | 111.1 (2) | C8—C14—H14 | 105.6 |
C5—C6—H6A | 109.4 | C13—C14—H14 | 105.6 |
C7—C6—H6A | 109.4 | C15—C14—H14 | 105.6 |
C5—C6—H6B | 109.4 | C16—C15—C14 | 114.33 (18) |
C7—C6—H6B | 109.4 | C16—C15—H15A | 108.7 |
H6A—C6—H6B | 108.0 | C14—C15—H15A | 108.7 |
C6—C7—C8 | 111.19 (18) | C16—C15—H15B | 108.7 |
C6—C7—H7A | 109.4 | C14—C15—H15B | 108.7 |
C8—C7—H7A | 109.4 | H15A—C15—H15B | 107.6 |
C6—C7—H7B | 109.4 | O2—C17—C20 | 119.3 (2) |
C8—C7—H7B | 109.4 | O2—C17—C13 | 120.2 (2) |
H7A—C7—H7B | 108.0 | C20—C17—C13 | 120.6 (2) |
C7—C8—C14 | 111.53 (16) | C13—C18—H18A | 109.5 |
C7—C8—C9 | 110.51 (16) | C13—C18—H18B | 109.5 |
C14—C8—C9 | 109.64 (14) | H18A—C18—H18B | 109.5 |
C7—C8—H8 | 108.4 | C13—C18—H18C | 109.5 |
C14—C8—H8 | 108.4 | H18A—C18—H18C | 109.5 |
C9—C8—H8 | 108.4 | H18B—C18—H18C | 109.5 |
C11—C9—C8 | 110.08 (16) | C10—C19—H19A | 109.5 |
C11—C9—C10 | 112.75 (16) | C10—C19—H19B | 109.5 |
C8—C9—C10 | 114.96 (15) | H19A—C19—H19B | 109.5 |
C11—C9—H9 | 106.1 | C10—C19—H19C | 109.5 |
C8—C9—H9 | 106.1 | H19A—C19—H19C | 109.5 |
C10—C9—H9 | 106.1 | H19B—C19—H19C | 109.5 |
C5—C10—C1 | 109.35 (19) | C17—C20—H20A | 109.5 |
C5—C10—C19 | 107.99 (17) | C17—C20—H20B | 109.5 |
C1—C10—C19 | 110.1 (2) | H20A—C20—H20B | 109.5 |
C5—C10—C9 | 109.92 (16) | C17—C20—H20C | 109.5 |
C1—C10—C9 | 107.81 (16) | H20A—C20—H20C | 109.5 |
C19—C10—C9 | 111.67 (17) | H20B—C20—H20C | 109.5 |
| | | |
C10—C1—C2—C3 | −54.3 (3) | C8—C9—C10—C1 | −163.94 (18) |
C1—C2—C3—O1 | −149.3 (3) | C11—C9—C10—C19 | −52.3 (2) |
C1—C2—C3—C4 | 33.0 (4) | C8—C9—C10—C19 | 75.0 (2) |
O1—C3—C4—C5 | 177.0 (3) | C8—C9—C11—C12 | 56.8 (2) |
C2—C3—C4—C5 | −5.2 (4) | C10—C9—C11—C12 | −173.38 (17) |
C2—C1—C10—C5 | 45.5 (3) | C9—C11—C12—C13 | −56.9 (2) |
C3—C4—C5—C6 | 175.1 (2) | C11—C12—C13—C18 | −69.4 (2) |
C3—C4—C5—C10 | −2.8 (4) | C11—C12—C13—C17 | 170.60 (17) |
C4—C5—C6—C7 | 128.2 (2) | C11—C12—C13—C14 | 54.4 (2) |
C4—C5—C10—C1 | −17.6 (3) | C7—C8—C14—C13 | −179.19 (17) |
C10—C5—C6—C7 | −53.8 (3) | C9—C8—C14—C13 | 58.1 (2) |
C5—C6—C7—C8 | 57.7 (3) | C7—C8—C14—C15 | −49.2 (2) |
C6—C7—C8—C9 | −56.6 (2) | C9—C8—C14—C15 | −171.97 (17) |
C6—C7—C8—C14 | −178.85 (19) | C18—C13—C14—C8 | 66.7 (2) |
C7—C8—C9—C11 | 179.92 (17) | C17—C13—C14—C8 | −168.23 (17) |
C14—C8—C9—C11 | −56.8 (2) | C12—C13—C14—C8 | −55.4 (2) |
C7—C8—C9—C10 | 51.3 (2) | C18—C13—C14—C15 | −63.6 (2) |
C14—C8—C9—C10 | 174.63 (16) | C17—C13—C14—C15 | 61.5 (2) |
C6—C5—C10—C1 | 164.4 (2) | C12—C13—C14—C15 | 174.28 (16) |
C4—C5—C10—C19 | 102.2 (3) | C8—C14—C15—C16 | −45.0 (3) |
C6—C5—C10—C19 | −75.8 (2) | C13—C14—C15—C16 | 85.1 (2) |
C6—C5—C10—C9 | 46.3 (3) | C18—C13—C17—O2 | 165.6 (3) |
C4—C5—C10—C9 | −135.8 (2) | C14—C13—C17—O2 | 39.7 (3) |
C2—C1—C10—C19 | −73.0 (3) | C12—C13—C17—O2 | −75.3 (3) |
C2—C1—C10—C9 | 165.0 (2) | C18—C13—C17—C20 | −16.4 (3) |
C11—C9—C10—C5 | −172.11 (18) | C14—C13—C17—C20 | −142.3 (3) |
C8—C9—C10—C5 | −44.8 (2) | C12—C13—C17—C20 | 102.7 (3) |
C11—C9—C10—C1 | 68.8 (2) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2A···O2i | 0.97 | 2.58 | 3.402 (4) | 142 (1) |
C20—H20B···O1i | 0.96 | 2.49 | 3.422 (4) | 167 (1) |
Symmetry code: (i) −x, y−1/2, −z+3/2. |
Experimental details
| (I) | (II) |
Crystal data |
Chemical formula | C22H31NO3 | C20H27NO2 |
Mr | 357.48 | 313.43 |
Crystal system, space group | Orthorhombic, P212121 | Orthorhombic, P212121 |
Temperature (K) | 293 | 293 |
a, b, c (Å) | 5.946 (2), 16.120 (2), 20.746 (3) | 8.929 (2), 10.022 (3), 19.651 (9) |
V (Å3) | 1988.5 (8) | 1758.5 (10) |
Z | 4 | 4 |
Radiation type | Cu Kα | Cu Kα |
µ (mm−1) | 0.62 | 0.59 |
Crystal size (mm) | 0.20 × 0.18 × 0.04 | 0.45 × 0.40 × 0.06 |
|
Data collection |
Diffractometer | Enraf–Nonius CAD-4 diffractometer | Enraf–Nonius CAD-4 diffractometer |
Absorption correction | – | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 6350, 2354, 1621 | 4254, 2073, 1723 |
Rint | 0.037 | 0.054 |
(sin θ/λ)max (Å−1) | 0.625 | 0.625 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.040, 0.136, 0.99 | 0.036, 0.119, 0.91 |
No. of reflections | 2354 | 2073 |
No. of parameters | 240 | 212 |
No. of restraints | 12 | 0 |
H-atom treatment | H-atom parameters constrained | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.21, −0.17 | 0.19, −0.14 |
Selected torsion angles (º) for (I) topC10—C1—C2—C3 | −55.8 (4) | C10—C5—C6—C7 | 3.1 (6) |
C1—C2—C3—C4 | 56.6 (4) | C5—C6—C7—C8 | 12.6 (5) |
C2—C3—C4—C5 | −54.5 (4) | C6—C7—C8—C9 | −44.1 (4) |
C2—C1—C10—C5 | 49.6 (4) | C7—C8—C9—C10 | 63.2 (3) |
C3—C4—C5—C10 | 52.5 (4) | C6—C5—C10—C9 | 14.5 (4) |
C4—C5—C10—C1 | −48.5 (4) | C8—C9—C10—C5 | −47.2 (3) |
Hydrogen-bond geometry (Å, º) for (I) top
D—H···A | D—H | H···A | D···A | D—H···A |
C20—H20B···O2i | 0.960 | 2.553 | 3.447 (5) | 154.9 (2) |
Symmetry code: (i) −x+1/2, −y, z−1/2. |
Selected torsion angles (º) for (II) topC10—C1—C2—C3 | −54.3 (3) | C10—C5—C6—C7 | −53.8 (3) |
C1—C2—C3—C4 | 33.0 (4) | C5—C6—C7—C8 | 57.7 (3) |
C2—C3—C4—C5 | −5.2 (4) | C6—C7—C8—C9 | −56.6 (2) |
C2—C1—C10—C5 | 45.5 (3) | C7—C8—C9—C10 | 51.3 (2) |
C3—C4—C5—C10 | −2.8 (4) | C6—C5—C10—C9 | 46.3 (3) |
C4—C5—C10—C1 | −17.6 (3) | C8—C9—C10—C5 | −44.8 (2) |
Hydrogen-bond geometry (Å, º) for (II) top
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2A···O2i | 0.970 | 2.583 | 3.402 (4) | 142.3 (2) |
C20—H20B···O1i | 0.960 | 2.486 | 3.422 (4) | 167.4 (2) |
Symmetry code: (i) −x, y−1/2, −z+3/2. |
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With the aim of studying anti-aromatase activity of some D-modified steroidal compounds, we have synthesized several new androstane derivatives (Penov-Gaši et al., 2001). Potent steroid aromatase inhibitors are mainly the A– and B-modified steroids, whereas the D-modified steroids (with the exception of testololactone) have received little research attention. Aromatase is a cytochrome P450 enzyme that catalyzes the conversion of androgens into estrogens at the last step of estrogen biosythesis (Thomson, 1974). Compounds that inhibit aromatase have potential applications in the treatment of advanced estrogen-dependent tumors, such as breast cancer, dometrial cancer, prostatic hyperplasia and prostate cancer. Within the framework of this project, we performed the structure analysis of the title compound, (I) and (II), respectively. The original basic crystallographic data have been deposited in the Cambridge Structural Database [CSD refcodes WULGAL, (I), and CCDC WULGEP, (II); Allen, 2002].
The structures of both compounds, deduced from chemical spectroscopic evidence, were confirmed by X-ray difraction analyses. Molecular-mechanics calculations (MMC) using PCMODEL (Serena Software, 1989) were also performed in order to define the conformation of the molecules in terms of energy minima. Since the starting materials were synthesized from the natural androstene derivative, the absolute stereochemistry of which is known (Fieser & Fieser, 1967), the X-ray structures are described for the appropriate enantiomer.
Perspective views of the molecules of (I) and (II) are shown in Figs. 1 and 2, respectively. The puckering (Cremer & Pople, 1975) and asymmetry parameters (Duax et al., 1976) reveal the following conformations. In (I), ring A has a 1α,4β-chair conformation, ring B has a 9α,8β-half-chair conformation and ring C adopts a 8β,12α-chair conformation. In (II), ring A exhibits a form intermediate between 1α-envelope and 1α,2β-half-chair, while rings B and C have 5α,8β- and 8β,12α-chair conformation, respectively.
The different conformations of rings A and B in (I) and (II), caused by the shifting of the double bond from C4=C5 in (I) to C5=C6 in (II), lead to significant differences in the steroid skeleton geometry in the region of rings A and B (Tables 1 and 3, and Fig. 3). Introducing the 4- and 5-double bonds into ring A of (I) and ring B of (II), respectively, also causes the twisting of the steroidal skeleton of each compound along the molecular principal axis, characterized by the values of the non-bonded C19—C10···C13—C18 torsion angles [5.7 (2) and 10.3 (2)° for (I) and (II), respectively]. The steroid geometries in the region of the C15 and C17 substituents (Fig.3) are similar. In the energy minimized models, this similarity is even more pronounced: ring A in (II) adopts an almost ideal 1E form, while the conformations of the other rings in (I) and (II) are not altered.
In the crystal packing of both compounds, molecules related by the screw axes are linked by weak hydrogen bonds, forming coils. In (I), C20—H20B···O2 bonds form coils along the c axis (Table 2); in (II), the C2—H2A···O2 and C20—H29B ···O1 bonds, in a `head-to-tail' and `tail-to-head' relationship, form coils along the b axis (Table 4).
The compounds were tested for possible anti-aromatase activity in the denucleated ovarian fractions from PMSG-pretreated female rats. For screening purposes, the compounds were tested in a single concentration (50 µM). The results showed that (I) exibited very low potency, while (II) completely inhibited aromatase activity in the presence of a subsaturated dose of testosterone, as well as in the presence of a saturated concentration (Penov-Gaši et al., 2001). The markedly greater biological activity of (II) can be interpreted as being due to the different molecular geometry in the region of rings A and B of the compounds, i.e. the presence of the 4-en-3-keto system instead of 5-en-3-acetoxy.