The title molecule, C
26H
30O
3, shows a novel chemical rearrangement of the substituents at position 17,
i.e. an
-orientation of the hydroxy group and a
-orientation of the bulky benzyl moiety. The packing arrangement consists of coils formed by O2
O3 hydrogen bonds along the
c axis. The compound shows complete loss of oestrogenic activity, and neither does it exhibit an antagonistic effect.
Supporting information
CCDC reference: 183011
The action of acidic aqueous TiCl3 upon
16-oximino-17α-benzyl-17β-hydroxy-16-hydroxyimino-3-methoxyestra-1,3,5(10)-
triene, (I), at room temperature afforded the title compound, (II), as the
main reaction product (78% yield; m.p. 385–387 K from methanol). The expected
fragmentation product, (III), was isolated only as a minor product in 10%
yield.
H atoms were generated and refined as riding groups, with C—H = 0.93–0.98 Å
and Uiso(H) = 1.2Ueq(carrier atom) or 1.5Ueq(methyl
C).
Data collection: PW1100 Software (Philips, 19??); cell refinement: PW1100 Software; data reduction: PW1100 Software; program(s) used to solve structure: SHELXS86 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: CSU (Vicković, 1988).
3-Methoxy-17
α-hydroxy-17
β-benzylestra-1,3,5(10)-trien-16-one
top
Crystal data top
C26H30O3 | Dx = 1.240 Mg m−3 |
Mr = 390.50 | Melting point = 385–387 K |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54180 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 20 reflections |
a = 36.426 (9) Å | θ = 6.6–12.8° |
b = 9.141 (1) Å | µ = 0.63 mm−1 |
c = 6.281 (2) Å | T = 293 K |
V = 2091.4 (9) Å3 | Prism, colourless |
Z = 4 | 0.47 × 0.07 × 0.03 mm |
F(000) = 840 | |
Data collection top
Philips PW1100 diffractometer | Rint = 0.066 |
Radiation source: fine-focus sealed tube | θmax = 70.0°, θmin = 4.9° |
Graphite monochromator | h = −43→44 |
ω/2θ scans | k = 0→11 |
3923 measured reflections | l = 0→7 |
2222 independent reflections | 3 standard reflections every 120 min |
1827 reflections with I > 2σ(I) | intensity decay: none |
Refinement top
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)] = 0.047 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.125 | H-atom parameters constrained |
S = 1.02 | w = 1/[σ2(Fo2) + (0.0461P)2 + 0.2999] where P = (Fo2 + 2Fc2)/3 |
2222 reflections | (Δ/σ)max < 0.001 |
263 parameters | Δρmax = 0.19 e Å−3 |
0 restraints | Δρmin = −0.19 e Å−3 |
Crystal data top
C26H30O3 | V = 2091.4 (9) Å3 |
Mr = 390.50 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 36.426 (9) Å | µ = 0.63 mm−1 |
b = 9.141 (1) Å | T = 293 K |
c = 6.281 (2) Å | 0.47 × 0.07 × 0.03 mm |
Data collection top
Philips PW1100 diffractometer | Rint = 0.066 |
3923 measured reflections | 3 standard reflections every 120 min |
2222 independent reflections | intensity decay: none |
1827 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.047 | 0 restraints |
wR(F2) = 0.125 | H-atom parameters constrained |
S = 1.02 | Δρmax = 0.19 e Å−3 |
2222 reflections | Δρmin = −0.19 e Å−3 |
263 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 | |
O1 | 0.58133 (7) | 0.4418 (3) | 0.5603 (5) | 0.0639 (8) | |
O2 | 0.30069 (6) | 0.5030 (3) | 0.5287 (4) | 0.0432 (6) | |
HO2 | 0.2782 | 0.5023 | 0.5308 | 0.065* | |
C1 | 0.48718 (9) | 0.5473 (4) | 0.7025 (6) | 0.0498 (9) | |
H1 | 0.4746 | 0.6048 | 0.8006 | 0.060* | |
C2 | 0.52519 (9) | 0.5416 (4) | 0.7138 (6) | 0.0509 (9) | |
H2 | 0.5379 | 0.5958 | 0.8153 | 0.061* | |
C3 | 0.54382 (9) | 0.4539 (4) | 0.5709 (6) | 0.0474 (8) | |
C4 | 0.52460 (9) | 0.3744 (4) | 0.4213 (6) | 0.0471 (8) | |
H4 | 0.5374 | 0.3153 | 0.3263 | 0.056* | |
C5 | 0.48654 (9) | 0.3804 (4) | 0.4091 (6) | 0.0436 (8) | |
C6 | 0.46726 (9) | 0.2895 (4) | 0.2410 (6) | 0.0546 (10) | |
H61 | 0.4772 | 0.1912 | 0.2436 | 0.066* | |
H62 | 0.4725 | 0.3310 | 0.1020 | 0.066* | |
C7 | 0.42590 (9) | 0.2811 (4) | 0.2702 (7) | 0.0498 (9) | |
H71 | 0.4201 | 0.2143 | 0.3854 | 0.060* | |
H72 | 0.4146 | 0.2441 | 0.1411 | 0.060* | |
C8 | 0.41064 (8) | 0.4326 (3) | 0.3208 (5) | 0.0376 (7) | |
H8 | 0.4197 | 0.5012 | 0.2131 | 0.045* | |
C9 | 0.42534 (9) | 0.4814 (4) | 0.5396 (5) | 0.0380 (7) | |
H9 | 0.4155 | 0.4129 | 0.6453 | 0.046* | |
C10 | 0.46702 (9) | 0.4704 (4) | 0.5501 (5) | 0.0401 (7) | |
C11 | 0.41115 (9) | 0.6352 (4) | 0.6001 (6) | 0.0435 (8) | |
H111 | 0.4186 | 0.6573 | 0.7448 | 0.052* | |
H112 | 0.4224 | 0.7070 | 0.5070 | 0.052* | |
C12 | 0.36936 (9) | 0.6487 (4) | 0.5834 (5) | 0.0404 (7) | |
H121 | 0.3580 | 0.5888 | 0.6927 | 0.048* | |
H122 | 0.3623 | 0.7495 | 0.6087 | 0.048* | |
C13 | 0.35526 (8) | 0.6011 (3) | 0.3661 (5) | 0.0320 (6) | |
C14 | 0.36903 (8) | 0.4423 (3) | 0.3255 (5) | 0.0349 (6) | |
H13 | 0.3608 | 0.3834 | 0.4469 | 0.042* | |
C15 | 0.34640 (9) | 0.3926 (4) | 0.1328 (5) | 0.0436 (8) | |
H151 | 0.3583 | 0.4199 | 0.0007 | 0.052* | |
H152 | 0.3428 | 0.2875 | 0.1345 | 0.052* | |
C16 | 0.31025 (8) | 0.4725 (4) | 0.1589 (5) | 0.0387 (7) | |
C17 | 0.31324 (8) | 0.5835 (3) | 0.3442 (5) | 0.0333 (6) | |
C18 | 0.36850 (9) | 0.7067 (4) | 0.1916 (6) | 0.0437 (8) | |
H181 | 0.3946 | 0.7188 | 0.2022 | 0.066* | |
H182 | 0.3567 | 0.7999 | 0.2095 | 0.066* | |
H183 | 0.3624 | 0.6675 | 0.0543 | 0.066* | |
C19 | 0.28993 (8) | 0.7185 (3) | 0.3048 (5) | 0.0378 (7) | |
H191 | 0.2644 | 0.6883 | 0.3022 | 0.045* | |
H192 | 0.2958 | 0.7554 | 0.1641 | 0.045* | |
C20 | 0.29345 (9) | 0.8438 (3) | 0.4608 (5) | 0.0362 (7) | |
C21 | 0.30859 (9) | 0.9771 (4) | 0.3986 (6) | 0.0433 (8) | |
H21 | 0.3179 | 0.9871 | 0.2615 | 0.052* | |
C22 | 0.31012 (10) | 1.0955 (4) | 0.5369 (7) | 0.0537 (9) | |
H22 | 0.3204 | 1.1833 | 0.4920 | 0.064* | |
C23 | 0.29634 (9) | 1.0831 (4) | 0.7417 (7) | 0.0514 (9) | |
H23 | 0.2971 | 1.1622 | 0.8346 | 0.062* | |
C24 | 0.28144 (9) | 0.9514 (4) | 0.8054 (6) | 0.0458 (8) | |
H24 | 0.2722 | 0.9420 | 0.9428 | 0.055* | |
C25 | 0.28001 (9) | 0.8331 (4) | 0.6687 (6) | 0.0403 (7) | |
H25 | 0.2700 | 0.7453 | 0.7156 | 0.048* | |
C26 | 0.60245 (10) | 0.5170 (5) | 0.7132 (8) | 0.0676 (12) | |
H261 | 0.6280 | 0.4984 | 0.6886 | 0.101* | |
H262 | 0.5959 | 0.4838 | 0.8531 | 0.101* | |
H263 | 0.5978 | 0.6201 | 0.7022 | 0.101* | |
O3 | 0.28249 (6) | 0.4515 (3) | 0.0552 (5) | 0.0579 (7) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0421 (12) | 0.0639 (16) | 0.086 (2) | 0.0100 (12) | −0.0096 (15) | −0.0129 (18) |
O2 | 0.0432 (12) | 0.0461 (13) | 0.0403 (12) | −0.0033 (11) | 0.0120 (11) | 0.0142 (12) |
C1 | 0.0457 (17) | 0.061 (2) | 0.0424 (17) | 0.0036 (16) | −0.0030 (16) | −0.0186 (19) |
C2 | 0.0495 (19) | 0.054 (2) | 0.0489 (19) | 0.0033 (16) | −0.0065 (17) | −0.0102 (19) |
C3 | 0.0414 (16) | 0.0443 (17) | 0.056 (2) | 0.0067 (15) | −0.0051 (17) | 0.0001 (19) |
C4 | 0.0502 (19) | 0.0439 (18) | 0.0470 (19) | 0.0124 (15) | 0.0003 (16) | −0.0100 (18) |
C5 | 0.0479 (17) | 0.0367 (15) | 0.0461 (18) | 0.0050 (14) | −0.0008 (16) | −0.0051 (16) |
C6 | 0.053 (2) | 0.059 (2) | 0.052 (2) | 0.0113 (18) | −0.0046 (18) | −0.022 (2) |
C7 | 0.0498 (19) | 0.0421 (17) | 0.058 (2) | 0.0047 (15) | −0.0077 (18) | −0.0174 (19) |
C8 | 0.0435 (16) | 0.0355 (15) | 0.0340 (15) | 0.0030 (13) | −0.0011 (14) | −0.0088 (15) |
C9 | 0.0447 (17) | 0.0398 (16) | 0.0295 (14) | 0.0022 (13) | 0.0025 (14) | −0.0052 (15) |
C10 | 0.0401 (15) | 0.0442 (16) | 0.0358 (15) | 0.0017 (14) | 0.0005 (14) | −0.0025 (16) |
C11 | 0.0438 (17) | 0.0490 (19) | 0.0378 (17) | 0.0027 (14) | −0.0013 (15) | −0.0194 (17) |
C12 | 0.0465 (17) | 0.0456 (17) | 0.0292 (15) | 0.0003 (15) | −0.0005 (14) | −0.0079 (15) |
C13 | 0.0388 (15) | 0.0327 (14) | 0.0246 (13) | −0.0064 (12) | 0.0036 (13) | −0.0037 (13) |
C14 | 0.0435 (15) | 0.0333 (14) | 0.0280 (14) | −0.0025 (13) | −0.0010 (14) | −0.0002 (14) |
C15 | 0.0491 (17) | 0.0423 (17) | 0.0394 (17) | −0.0027 (15) | −0.0044 (16) | −0.0120 (16) |
C16 | 0.0387 (16) | 0.0388 (16) | 0.0388 (16) | −0.0077 (14) | −0.0022 (14) | −0.0022 (16) |
C17 | 0.0396 (15) | 0.0322 (14) | 0.0281 (14) | −0.0038 (12) | 0.0035 (13) | 0.0025 (14) |
C18 | 0.0455 (17) | 0.0406 (17) | 0.0449 (18) | −0.0042 (15) | 0.0144 (17) | 0.0064 (17) |
C19 | 0.0375 (15) | 0.0395 (15) | 0.0363 (16) | −0.0023 (13) | −0.0022 (14) | 0.0003 (15) |
C20 | 0.0387 (15) | 0.0352 (14) | 0.0346 (16) | 0.0053 (13) | −0.0003 (14) | 0.0035 (14) |
C21 | 0.0428 (17) | 0.0430 (17) | 0.0441 (18) | −0.0053 (14) | 0.0013 (15) | 0.0063 (17) |
C22 | 0.053 (2) | 0.0410 (18) | 0.067 (2) | −0.0052 (16) | −0.004 (2) | −0.002 (2) |
C23 | 0.0448 (18) | 0.0483 (19) | 0.061 (2) | 0.0093 (16) | −0.0105 (18) | −0.0138 (19) |
C24 | 0.0434 (17) | 0.0533 (19) | 0.0406 (17) | 0.0127 (16) | −0.0040 (16) | −0.0029 (18) |
C25 | 0.0430 (16) | 0.0382 (15) | 0.0398 (17) | 0.0047 (14) | 0.0028 (15) | 0.0027 (16) |
C26 | 0.050 (2) | 0.065 (2) | 0.088 (3) | 0.0043 (19) | −0.017 (2) | 0.000 (3) |
O3 | 0.0452 (13) | 0.0674 (16) | 0.0611 (16) | −0.0090 (12) | −0.0136 (13) | −0.0174 (16) |
Geometric parameters (Å, º) top
O1—C3 | 1.372 (4) | C13—C18 | 1.538 (4) |
O1—C26 | 1.410 (5) | C13—C17 | 1.545 (4) |
O2—C17 | 1.446 (4) | C13—C14 | 1.557 (4) |
O2—HO2 | 0.8200 | C14—C15 | 1.533 (4) |
C1—C2 | 1.387 (5) | C14—H13 | 0.9800 |
C1—C10 | 1.396 (5) | C15—C16 | 1.515 (4) |
C1—H1 | 0.9300 | C15—H151 | 0.9700 |
C2—C3 | 1.382 (5) | C15—H152 | 0.9700 |
C2—H2 | 0.9300 | C16—O3 | 1.218 (4) |
C3—C4 | 1.379 (5) | C16—C17 | 1.548 (4) |
C4—C5 | 1.390 (5) | C17—C19 | 1.518 (4) |
C4—H4 | 0.9300 | C18—H181 | 0.9600 |
C5—C10 | 1.403 (5) | C18—H182 | 0.9600 |
C5—C6 | 1.516 (5) | C18—H183 | 0.9600 |
C6—C7 | 1.520 (5) | C19—C20 | 1.513 (4) |
C6—H61 | 0.9700 | C19—H191 | 0.9700 |
C6—H62 | 0.9700 | C19—H192 | 0.9700 |
C7—C8 | 1.526 (4) | C20—C21 | 1.394 (4) |
C7—H71 | 0.9700 | C20—C25 | 1.398 (5) |
C7—H72 | 0.9700 | C21—C22 | 1.388 (5) |
C8—C14 | 1.519 (4) | C21—H21 | 0.9300 |
C8—C9 | 1.541 (4) | C22—C23 | 1.385 (6) |
C8—H8 | 0.9800 | C22—H22 | 0.9300 |
C9—C10 | 1.523 (4) | C23—C24 | 1.380 (5) |
C9—C11 | 1.546 (4) | C23—H23 | 0.9300 |
C9—H9 | 0.9800 | C24—C25 | 1.382 (5) |
C11—C12 | 1.531 (4) | C24—H24 | 0.9300 |
C11—H111 | 0.9700 | C25—H25 | 0.9300 |
C11—H112 | 0.9700 | C26—H261 | 0.9600 |
C12—C13 | 1.522 (4) | C26—H262 | 0.9600 |
C12—H121 | 0.9700 | C26—H263 | 0.9600 |
C12—H122 | 0.9700 | | |
| | | |
C3—O1—C26 | 118.1 (3) | C18—C13—C14 | 111.6 (2) |
C17—O2—HO2 | 109.5 | C17—C13—C14 | 102.0 (2) |
C2—C1—C10 | 122.7 (3) | C8—C14—C15 | 120.3 (3) |
C2—C1—H1 | 118.6 | C8—C14—C13 | 112.3 (2) |
C10—C1—H1 | 118.6 | C15—C14—C13 | 103.4 (2) |
C3—C2—C1 | 118.6 (3) | C8—C14—H13 | 106.7 |
C3—C2—H2 | 120.7 | C15—C14—H13 | 106.7 |
C1—C2—H2 | 120.7 | C13—C14—H13 | 106.7 |
O1—C3—C4 | 115.5 (3) | C16—C15—C14 | 103.9 (3) |
O1—C3—C2 | 124.6 (3) | C16—C15—H151 | 111.0 |
C4—C3—C2 | 119.9 (3) | C14—C15—H151 | 111.0 |
C3—C4—C5 | 121.5 (3) | C16—C15—H152 | 111.0 |
C3—C4—H4 | 119.2 | C14—C15—H152 | 111.0 |
C5—C4—H4 | 119.2 | H151—C15—H152 | 109.0 |
C4—C5—C10 | 119.6 (3) | O3—C16—C15 | 126.0 (3) |
C4—C5—C6 | 118.6 (3) | O3—C16—C17 | 124.3 (3) |
C10—C5—C6 | 121.8 (3) | C15—C16—C17 | 109.6 (3) |
C5—C6—C7 | 113.8 (3) | O2—C17—C19 | 111.5 (3) |
C5—C6—H61 | 108.8 | O2—C17—C13 | 107.1 (2) |
C7—C6—H61 | 108.8 | C19—C17—C13 | 119.0 (2) |
C5—C6—H62 | 108.8 | O2—C17—C16 | 104.3 (2) |
C7—C6—H62 | 108.8 | C19—C17—C16 | 111.7 (3) |
H61—C6—H62 | 107.7 | C13—C17—C16 | 101.8 (2) |
C6—C7—C8 | 109.9 (3) | C13—C18—H181 | 109.5 |
C6—C7—H71 | 109.7 | C13—C18—H182 | 109.5 |
C8—C7—H71 | 109.7 | H181—C18—H182 | 109.5 |
C6—C7—H72 | 109.7 | C13—C18—H183 | 109.5 |
C8—C7—H72 | 109.7 | H181—C18—H183 | 109.5 |
H71—C7—H72 | 108.2 | H182—C18—H183 | 109.5 |
C14—C8—C7 | 114.9 (3) | C17—C19—C20 | 117.5 (3) |
C14—C8—C9 | 108.2 (3) | C17—C19—H191 | 107.9 |
C7—C8—C9 | 108.8 (3) | C20—C19—H191 | 107.9 |
C14—C8—H8 | 108.3 | C17—C19—H192 | 107.9 |
C7—C8—H8 | 108.3 | C20—C19—H192 | 107.9 |
C9—C8—H8 | 108.3 | H191—C19—H192 | 107.2 |
C10—C9—C8 | 111.5 (3) | C21—C20—C25 | 117.5 (3) |
C10—C9—C11 | 112.5 (3) | C21—C20—C19 | 121.0 (3) |
C8—C9—C11 | 111.5 (3) | C25—C20—C19 | 121.5 (3) |
C10—C9—H9 | 107.0 | C20—C21—C22 | 121.5 (3) |
C8—C9—H9 | 107.0 | C20—C21—H21 | 119.3 |
C11—C9—H9 | 107.0 | C22—C21—H21 | 119.3 |
C1—C10—C5 | 117.5 (3) | C21—C22—C23 | 120.2 (4) |
C1—C10—C9 | 121.4 (3) | C21—C22—H22 | 119.9 |
C5—C10—C9 | 121.1 (3) | C23—C22—H22 | 119.9 |
C12—C11—C9 | 112.9 (3) | C24—C23—C22 | 118.9 (4) |
C12—C11—H111 | 109.0 | C24—C23—H23 | 120.6 |
C9—C11—H111 | 109.0 | C22—C23—H23 | 120.6 |
C12—C11—H112 | 109.0 | C23—C24—C25 | 121.1 (3) |
C9—C11—H112 | 109.0 | C23—C24—H24 | 119.4 |
H111—C11—H112 | 107.8 | C25—C24—H24 | 119.4 |
C13—C12—C11 | 111.9 (3) | C24—C25—C20 | 120.9 (3) |
C13—C12—H121 | 109.2 | C24—C25—H25 | 119.6 |
C11—C12—H121 | 109.2 | C20—C25—H25 | 119.6 |
C13—C12—H122 | 109.2 | O1—C26—H261 | 109.5 |
C11—C12—H122 | 109.2 | O1—C26—H262 | 109.5 |
H121—C12—H122 | 107.9 | H261—C26—H262 | 109.5 |
C12—C13—C18 | 110.7 (2) | O1—C26—H263 | 109.5 |
C12—C13—C17 | 116.3 (3) | H261—C26—H263 | 109.5 |
C18—C13—C17 | 108.2 (3) | H262—C26—H263 | 109.5 |
C12—C13—C14 | 107.8 (3) | | |
| | | |
C10—C1—C2—C3 | −1.3 (6) | C12—C13—C14—C8 | −61.7 (3) |
C26—O1—C3—C4 | −178.1 (3) | C18—C13—C14—C8 | 60.1 (4) |
C26—O1—C3—C2 | 4.0 (6) | C17—C13—C14—C8 | 175.4 (3) |
C1—C2—C3—O1 | 177.9 (4) | C12—C13—C14—C15 | 167.2 (2) |
C1—C2—C3—C4 | 0.0 (6) | C18—C13—C14—C15 | −71.1 (3) |
O1—C3—C4—C5 | −177.8 (3) | C17—C13—C14—C15 | 44.2 (3) |
C2—C3—C4—C5 | 0.3 (6) | C8—C14—C15—C16 | −158.0 (3) |
C3—C4—C5—C10 | 0.7 (6) | C13—C14—C15—C16 | −31.7 (3) |
C3—C4—C5—C6 | −179.8 (3) | C14—C15—C16—O3 | −170.5 (3) |
C4—C5—C6—C7 | 168.6 (3) | C14—C15—C16—C17 | 7.8 (4) |
C10—C5—C6—C7 | −12.0 (5) | C12—C13—C17—O2 | −45.8 (3) |
C5—C6—C7—C8 | 44.8 (5) | C18—C13—C17—O2 | −171.1 (2) |
C6—C7—C8—C14 | 172.5 (3) | C14—C13—C17—O2 | 71.1 (3) |
C6—C7—C8—C9 | −66.1 (4) | C12—C13—C17—C19 | 81.8 (4) |
C14—C8—C9—C10 | 178.3 (3) | C18—C13—C17—C19 | −43.5 (4) |
C7—C8—C9—C10 | 52.9 (4) | C14—C13—C17—C19 | −161.3 (3) |
C14—C8—C9—C11 | −55.1 (3) | C12—C13—C17—C16 | −155.0 (3) |
C7—C8—C9—C11 | 179.5 (3) | C18—C13—C17—C16 | 79.7 (3) |
C2—C1—C10—C5 | 2.3 (6) | C14—C13—C17—C16 | −38.0 (3) |
C2—C1—C10—C9 | −178.8 (4) | O3—C16—C17—O2 | 86.2 (4) |
C4—C5—C10—C1 | −1.9 (5) | C15—C16—C17—O2 | −92.1 (3) |
C6—C5—C10—C1 | 178.6 (3) | O3—C16—C17—C19 | −34.5 (4) |
C4—C5—C10—C9 | 179.2 (3) | C15—C16—C17—C19 | 147.3 (3) |
C6—C5—C10—C9 | −0.3 (5) | O3—C16—C17—C13 | −162.5 (3) |
C8—C9—C10—C1 | 160.6 (3) | C15—C16—C17—C13 | 19.3 (3) |
C11—C9—C10—C1 | 34.5 (5) | O2—C17—C19—C20 | 70.4 (3) |
C8—C9—C10—C5 | −20.6 (4) | C13—C17—C19—C20 | −55.1 (4) |
C11—C9—C10—C5 | −146.6 (3) | C16—C17—C19—C20 | −173.3 (3) |
C10—C9—C11—C12 | 178.2 (3) | C17—C19—C20—C21 | 113.0 (3) |
C8—C9—C11—C12 | 52.2 (4) | C17—C19—C20—C25 | −70.3 (4) |
C9—C11—C12—C13 | −53.1 (4) | C25—C20—C21—C22 | −0.4 (5) |
C11—C12—C13—C18 | −66.6 (4) | C19—C20—C21—C22 | 176.4 (3) |
C11—C12—C13—C17 | 169.4 (3) | C20—C21—C22—C23 | −0.2 (5) |
C11—C12—C13—C14 | 55.7 (3) | C21—C22—C23—C24 | 0.5 (5) |
C7—C8—C14—C15 | −55.0 (4) | C22—C23—C24—C25 | −0.2 (5) |
C9—C8—C14—C15 | −176.7 (3) | C23—C24—C25—C20 | −0.4 (5) |
C7—C8—C14—C13 | −177.0 (3) | C21—C20—C25—C24 | 0.7 (5) |
C9—C8—C14—C13 | 61.3 (3) | C19—C20—C25—C24 | −176.1 (3) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O2—HO2···O3i | 0.82 | 2.25 | 3.063 (4) | 168 |
Symmetry code: (i) −x+1/2, −y+1, z+1/2. |
Experimental details
Crystal data |
Chemical formula | C26H30O3 |
Mr | 390.50 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 293 |
a, b, c (Å) | 36.426 (9), 9.141 (1), 6.281 (2) |
V (Å3) | 2091.4 (9) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.63 |
Crystal size (mm) | 0.47 × 0.07 × 0.03 |
|
Data collection |
Diffractometer | Philips PW1100 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3923, 2222, 1827 |
Rint | 0.066 |
(sin θ/λ)max (Å−1) | 0.610 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.047, 0.125, 1.02 |
No. of reflections | 2222 |
No. of parameters | 263 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.19, −0.19 |
Selected bond lengths (Å) topO1—C3 | 1.372 (4) | O2—C17 | 1.446 (4) |
O1—C26 | 1.410 (5) | C16—O3 | 1.218 (4) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O2—HO2···O3i | 0.82 | 2.252 | 3.063 (4) | 168 |
Symmetry code: (i) −x+1/2, −y+1, z+1/2. |
In our earlier reports (Miljković et al., 1973, 1978; Miljković & Petrović, 1977; Miljković & Gaši, 1981), we established that D-ring fragmentation occurs in selected 16-oximino-17β-hydroxy steroid derivatives, under the conditions of the Beckmann reaction, affording the corresponding 16,17-seco-16-cyano-17-oxo-derivatives in reasonable yields. While continuing the study of the Beckmann fragmentation reaction, we have now unexpectedly discovered a novel rearrangement reaction.
By the action of acidic aqueous TiCl3 (a reagent which caused fragmentation in all earlier cases) upon 16-oximino-17α-benzyl-17β-hydroxy derivatives in the androstane and estrane series, 16-oxo-17β-benzyl-17α-hydroxy derivatives with the inverse configuration at C17 were obtained (Miljković et al., 1997). Thus, acidic aqueous TiCl3 mainly caused the hydrolysis of the 16-oximino group to the corresponding 16-keto group, with simultaneous rearrangement of the benzyl substituent from the 17α to the 17β position. The same rearrangement reaction was observed in the case of α-oxyimino alcohol, (I) (Stanković et al., 1996), which afforded compound (II) as the main reaction product under analogous reaction conditions. The intended and expected fragmentation product, (III), was isolated only as a minor product in 10% yield. \sch
The crude structure of (II) was deduced on the basis of spectroscopic evidence. Subsequently, X-ray diffraction analysis revealed the detailed structure, indicating a novel chemical rearrangement, described recently by Miljković et al. (1997), i.e. the migration of the benzyl substituent from the 17α-position in (I) to the 17β-position in (II).
Fig. 1 shows a perspective view of the molecule of (II). Since the starting materials were synthesized from the natural oestrone, the absolute stereochemistry of which is known (Fieser & Fieser, 1967), the X-ray structure of (II) is described for the appropriate enantiomer. The puckering (Cremer & Pople, 1975) and asymmetry parameters (Duax et al., 1976) reveal the usual ring conformations: ring B is a 7α,8β half-chair, ring C has a chair conformation, and ring D exhibits a transitional form between a 13β envelope and a 13β,14α half-chair conformation.
The C1—C10···C13—C18 non-bonded torsion angle of 88.1 (3)° shows that there is no significant twist along the principal axis of the molecule. The conformation of the steroidal skeleton of (II) compared with its precursor, (I), shows no significant difference (Fig. 2). Even so, the orientations of the two substituents at C17 are reversed. Biological screening demonstrated that (II) showed a complete loss of oestrogenic activity, which was considerable in (I) (a dose of 25 mg kg-1 in experimental animals showed 74.98% of agonistic activity), as well as an absence of antagonistic effect. The unexpected α-orientation of the bulky substituent is thought to be the main reason for this significant change of biological activity (Duax et al., 1976).
In the crystal packing of (II), molecules related by the screw axis are linked by O2···O3 hydrogen bonds (Table 2), forming coils along the c axis.