Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536805040912/tk6295sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536805040912/tk6295IIsup2.hkl |
CCDC reference: 296686
A solution of sodium ethoxide (1.243 M, 5 ml) was added slowly to a stirred solution of dehydroisoandrosterone (600 mg, 2 mmol) and triethyl phosphonoacetate (1.6 ml, 6 mmol) in ethanol (5 ml) at room temperature, under an N2 atmosphere. The reaction mixture was refluxed for 20 h, then cooled to room temperature and concentrated in vacuo. The residue was diluted with water and the resulting suspension acidified (acetic acid) and extracted with a mixture of ethyl acetate and tetrahydrofuran (3:1, 60 ml). The organic layer was washed with water and brine, dried (Na2SO4) and the solvent removed by evaporation at reduced pressure. Crystallization of the residue from methanol gave the product ethyl 3β-hydroxypregna-5,17 (20)-dien-21-oate (525 mg, 70%) as fine colourless crystals, suitable for X-ray crystallographic analysis [m.p.: 457–9 K; literature 457–458 K (Wicha et al., 1977)]. 1H NMR (400 MHz, CDCl3, 298 K): δ 5.51 (1H, dd, J = 2.5, 2.5 Hz, H2O), 5.32 (1H, m, H6), 4.11 (2H, m, CH2, H22), 3.49 (1H, dddd, J = 4, 5, 11, 11 Hz, H3), 2.88–2.72 (2H, m, H16a,b), 2.31–2.15 (2H, m, H4a,b), 2.03 (1H, m, H7a), 1.85–1.72 (4H, br m, H12a, H15a, H1a, H2a), 1.68–1.41 (5H, br m, H11a,b, H8, H2b, H7b), 1.38–1.20 (2H, br m, H15b, H12b), 1.22 (3H, dd, CH3, H23), 1.10–0.91 (3H, m, H1b, H14, H9), 0.99 (3H, s, CH3, H19), 0.80 (3H, s, CH3, H18); 13C{1H} NMR (100 MHz, CDCl3, 298 K): δ 176.15 (C17), 167.45 (C═O, C21), 140.82 (C5), 121.28 (C6), 108.62 (C20), 71.61 (C3), 59.50 (C22), 53.81 (C14), 50.21 (C9), 46.03 (C13), 42.20 (C4), 37.20 (C1), 36.56 (C10), 35.18 (C12), 31.64–31.55 (C7, C2, C8), 30.41 (C16), 24.45 (C15), 20.94 (C11), 19.39 (C19), 18.23 (C18), 14.36 (C23). ESMS (m/z): +ve ion, 381.15 [M + Na]+, 359.13, [M + H] +.
C-bound H atoms were constrained as riding atoms, with C—H = 0.94–0.96 Å, and with Uiso(H)= 1.2Ueq(parent atom). The hydroxy H atom was located in a difference Fourier synthesis and constrained as a riding atom, with O—H = 0.91 Å. In the absence of significant anomalous scattering effects, Friedel pairs were merged. The absolute configuration is assigned on the basis of the known configuration of the starting material.
Data collection: MSC/AFC7 Diffractometer Control Software for Windows (Molecular Structure Corporation, 1999); cell refinement: MSC/AFC7 Diffractometer Control Software for Windows; data reduction: TEXSAN for Windows (Molecular Structure Corporation, 2001); program(s) used to solve structure: TEXSAN for Windows; program(s) used to refine structure: TEXSAN for Windows and SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: TEXSAN for Windows and PLATON (Spek, 2003).
Fig. 1. Representative view of (II), with the atom-numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 30% probability level. |
C23H34O3 | Z = 1 |
Mr = 358.50 | F(000) = 196 |
Triclinic, P1 | Dx = 1.187 Mg m−3 |
Hall symbol: P 1 | Mo Kα radiation, λ = 0.7107 Å |
a = 6.3179 (17) Å | Cell parameters from 25 reflections |
b = 8.0901 (16) Å | θ = 12.7–17.3° |
c = 10.880 (2) Å | µ = 0.08 mm−1 |
α = 73.8 (2)° | T = 295 K |
β = 100.311 (19)° | Prism, colourless |
γ = 109.285 (16)° | 0.40 × 0.35 × 0.20 mm |
V = 501.7 (5) Å3 |
Rigaku AFC-7R diffractometer | Rint = 0.033 |
Radiation source: Rigaku rotating anode | θmax = 25.0°, θmin = 2.8° |
Graphite monochromator | h = −7→7 |
ω–2θ scans | k = 0→9 |
2086 measured reflections | l = −11→12 |
1756 independent reflections | 3 standard reflections every 150 reflections |
1506 reflections with I > 2σ(I) | intensity decay: 1.2% |
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)] = 0.041 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.111 | H-atom parameters constrained |
S = 1.04 | w = 1/[σ2(Fo2) + (0.0611P)2 + 0.0627P] where P = (Fo2 + 2Fc2)/3 |
1756 reflections | (Δ/σ)max = 0.023 |
235 parameters | Δρmax = 0.15 e Å−3 |
3 restraints | Δρmin = −0.19 e Å−3 |
C23H34O3 | γ = 109.285 (16)° |
Mr = 358.50 | V = 501.7 (5) Å3 |
Triclinic, P1 | Z = 1 |
a = 6.3179 (17) Å | Mo Kα radiation |
b = 8.0901 (16) Å | µ = 0.08 mm−1 |
c = 10.880 (2) Å | T = 295 K |
α = 73.8 (2)° | 0.40 × 0.35 × 0.20 mm |
β = 100.311 (19)° |
Rigaku AFC-7R diffractometer | Rint = 0.033 |
2086 measured reflections | 3 standard reflections every 150 reflections |
1756 independent reflections | intensity decay: 1.2% |
1506 reflections with I > 2σ(I) |
R[F2 > 2σ(F2)] = 0.041 | 3 restraints |
wR(F2) = 0.111 | H-atom parameters constrained |
S = 1.04 | Δρmax = 0.15 e Å−3 |
1756 reflections | Δρmin = −0.19 e Å−3 |
235 parameters |
Experimental. The scan width was (1.73 + 0.30tanθ)° with an ω scan speed of 16° per minute (up to 4 scans to achieve I/σ(I) > 10). Stationary background counts were recorded at each end of the scan, and the scan time:background time ratio was 2:1. |
Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles |
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 > 2σ(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 | ||
O3 | 1.0849 (4) | 0.9636 (3) | 1.1570 (2) | 0.0604 (9) | |
O21 | −0.0540 (5) | 0.2129 (3) | 0.2577 (3) | 0.0655 (9) | |
O22 | −0.2529 (4) | 0.4108 (3) | 0.1955 (2) | 0.0536 (8) | |
C1 | 0.6876 (5) | 0.9347 (4) | 0.8535 (3) | 0.0473 (10) | |
C2 | 0.8309 (7) | 1.0190 (5) | 0.9610 (4) | 0.0543 (11) | |
C3 | 0.9404 (6) | 0.8873 (4) | 1.0563 (3) | 0.0476 (10) | |
C4 | 1.0809 (6) | 0.8287 (4) | 0.9877 (3) | 0.0477 (10) | |
C5 | 0.9449 (5) | 0.7482 (4) | 0.8786 (3) | 0.0413 (9) | |
C6 | 0.9428 (6) | 0.5873 (5) | 0.8702 (3) | 0.0492 (11) | |
C7 | 0.8129 (6) | 0.4944 (5) | 0.7670 (3) | 0.0517 (11) | |
C8 | 0.7240 (5) | 0.6185 (4) | 0.6518 (3) | 0.0407 (9) | |
C9 | 0.6315 (5) | 0.7437 (4) | 0.6964 (3) | 0.0380 (9) | |
C10 | 0.8103 (5) | 0.8621 (4) | 0.7802 (3) | 0.0390 (9) | |
C11 | 0.5107 (6) | 0.8535 (4) | 0.5832 (3) | 0.0477 (11) | |
C12 | 0.3327 (5) | 0.7395 (4) | 0.5006 (3) | 0.0461 (10) | |
C13 | 0.4329 (5) | 0.6232 (4) | 0.4540 (3) | 0.0388 (9) | |
C14 | 0.5359 (5) | 0.5092 (4) | 0.5720 (3) | 0.0393 (9) | |
C15 | 0.5749 (6) | 0.3668 (5) | 0.5194 (3) | 0.0490 (11) | |
C16 | 0.3638 (6) | 0.3179 (4) | 0.4260 (3) | 0.0476 (10) | |
C17 | 0.2711 (5) | 0.4778 (4) | 0.3912 (3) | 0.0403 (10) | |
C18 | 0.6053 (6) | 0.7415 (5) | 0.3549 (3) | 0.0529 (11) | |
C19 | 0.9796 (6) | 1.0199 (5) | 0.6967 (4) | 0.0552 (11) | |
C20 | 0.0809 (5) | 0.4933 (4) | 0.3200 (3) | 0.0451 (10) | |
C21 | −0.0754 (5) | 0.3561 (5) | 0.2572 (3) | 0.0465 (10) | |
C22 | −0.4185 (6) | 0.2935 (5) | 0.1228 (4) | 0.0600 (12) | |
C23 | −0.5828 (6) | 0.3922 (5) | 0.0518 (4) | 0.0636 (12) | |
H3 | 1.02330 | 1.03750 | 1.17800 | 0.0680* | |
H6 | 1.03110 | 0.52540 | 0.93550 | 0.0580* | |
H8 | 0.84270 | 0.68880 | 0.60100 | 0.0490* | |
H9 | 0.51800 | 0.66630 | 0.75150 | 0.0450* | |
H11 | 0.56550 | 0.83720 | 0.89060 | 0.0560* | |
H12 | 0.63010 | 1.02350 | 0.79400 | 0.0560* | |
H14 | 0.41730 | 0.44590 | 0.62690 | 0.0460* | |
H20 | 0.04360 | 0.60120 | 0.31020 | 0.0540* | |
H21 | 0.94470 | 1.12310 | 0.92560 | 0.0640* | |
H22 | 0.73810 | 1.05070 | 1.00490 | 0.0640* | |
H31 | 0.82550 | 0.78360 | 1.09440 | 0.0570* | |
H41 | 1.19990 | 0.93000 | 0.95550 | 0.0570* | |
H42 | 1.14020 | 0.74060 | 1.04860 | 0.0570* | |
H71 | 0.68710 | 0.39880 | 0.80360 | 0.0620* | |
H72 | 0.90680 | 0.44530 | 0.73960 | 0.0620* | |
H111 | 0.43870 | 0.91470 | 0.61760 | 0.0560* | |
H112 | 0.62000 | 0.93790 | 0.52990 | 0.0560* | |
H121 | 0.21180 | 0.66350 | 0.55130 | 0.0550* | |
H122 | 0.27690 | 0.81660 | 0.42930 | 0.0550* | |
H151 | 0.70730 | 0.41410 | 0.47690 | 0.0580* | |
H152 | 0.58600 | 0.26460 | 0.58760 | 0.0580* | |
H161 | 0.40180 | 0.29920 | 0.35190 | 0.0560* | |
H162 | 0.25560 | 0.21090 | 0.46690 | 0.0560* | |
H181 | 0.69840 | 0.84430 | 0.38560 | 0.0630* | |
H182 | 0.52650 | 0.77950 | 0.27510 | 0.0630* | |
H183 | 0.69540 | 0.67360 | 0.34590 | 0.0630* | |
H191 | 1.08670 | 1.08810 | 0.75170 | 0.0670* | |
H192 | 0.90120 | 1.09440 | 0.63730 | 0.0670* | |
H193 | 1.05470 | 0.97300 | 0.65340 | 0.0670* | |
H221 | −0.49310 | 0.18340 | 0.17920 | 0.0720* | |
H222 | −0.34690 | 0.26680 | 0.06410 | 0.0720* | |
H231 | −0.68030 | 0.32940 | −0.00790 | 0.0740* | |
H232 | −0.50390 | 0.50950 | 0.00990 | 0.0740* | |
H233 | −0.67130 | 0.39910 | 0.11270 | 0.0740* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O3 | 0.0694 (17) | 0.0574 (15) | 0.0578 (15) | 0.0215 (13) | −0.0096 (12) | −0.0256 (12) |
O21 | 0.0603 (15) | 0.0517 (14) | 0.0918 (19) | 0.0223 (12) | −0.0096 (14) | −0.0320 (14) |
O22 | 0.0453 (12) | 0.0567 (14) | 0.0646 (15) | 0.0168 (11) | −0.0063 (11) | −0.0289 (12) |
C1 | 0.0460 (17) | 0.0456 (18) | 0.0565 (19) | 0.0218 (15) | −0.0024 (14) | −0.0167 (15) |
C2 | 0.061 (2) | 0.0469 (19) | 0.061 (2) | 0.0210 (16) | −0.0036 (17) | −0.0220 (16) |
C3 | 0.0504 (18) | 0.0421 (17) | 0.0492 (18) | 0.0090 (14) | 0.0013 (14) | −0.0170 (14) |
C4 | 0.0463 (17) | 0.0469 (18) | 0.0483 (18) | 0.0170 (14) | −0.0020 (14) | −0.0091 (15) |
C5 | 0.0375 (15) | 0.0445 (17) | 0.0418 (16) | 0.0152 (13) | 0.0052 (12) | −0.0055 (14) |
C6 | 0.0539 (19) | 0.0530 (19) | 0.0458 (17) | 0.0297 (15) | −0.0097 (14) | −0.0120 (14) |
C7 | 0.065 (2) | 0.0505 (19) | 0.0487 (19) | 0.0343 (17) | −0.0079 (16) | −0.0136 (15) |
C8 | 0.0443 (17) | 0.0385 (15) | 0.0414 (16) | 0.0179 (13) | 0.0036 (13) | −0.0062 (13) |
C9 | 0.0381 (15) | 0.0366 (15) | 0.0411 (16) | 0.0151 (12) | 0.0069 (12) | −0.0053 (13) |
C10 | 0.0349 (15) | 0.0361 (15) | 0.0437 (16) | 0.0118 (12) | 0.0029 (12) | −0.0050 (12) |
C11 | 0.0546 (19) | 0.0416 (17) | 0.0525 (19) | 0.0265 (15) | −0.0079 (15) | −0.0135 (15) |
C12 | 0.0440 (17) | 0.0453 (17) | 0.0524 (19) | 0.0234 (14) | −0.0053 (14) | −0.0109 (15) |
C13 | 0.0369 (15) | 0.0367 (15) | 0.0388 (16) | 0.0113 (12) | 0.0030 (13) | −0.0027 (13) |
C14 | 0.0413 (16) | 0.0376 (15) | 0.0402 (16) | 0.0180 (13) | 0.0077 (13) | −0.0013 (13) |
C15 | 0.0550 (19) | 0.0446 (17) | 0.0519 (19) | 0.0242 (15) | 0.0003 (16) | −0.0100 (15) |
C16 | 0.0552 (19) | 0.0414 (16) | 0.0478 (18) | 0.0180 (15) | 0.0043 (15) | −0.0093 (14) |
C17 | 0.0441 (17) | 0.0376 (16) | 0.0394 (17) | 0.0130 (13) | 0.0098 (13) | −0.0049 (13) |
C18 | 0.0519 (19) | 0.0521 (19) | 0.0427 (17) | 0.0075 (15) | 0.0092 (14) | 0.0012 (15) |
C19 | 0.0463 (18) | 0.0489 (19) | 0.055 (2) | 0.0030 (15) | 0.0024 (15) | −0.0029 (16) |
C20 | 0.0442 (17) | 0.0393 (17) | 0.0538 (19) | 0.0154 (13) | 0.0014 (14) | −0.0124 (14) |
C21 | 0.0433 (17) | 0.0486 (18) | 0.0518 (19) | 0.0147 (14) | 0.0078 (14) | −0.0154 (15) |
C22 | 0.052 (2) | 0.062 (2) | 0.067 (2) | 0.0109 (17) | −0.0031 (17) | −0.0298 (19) |
C23 | 0.048 (2) | 0.061 (2) | 0.067 (2) | 0.0049 (17) | −0.0090 (17) | −0.0147 (18) |
O3—C3 | 1.436 (4) | C2—H21 | 0.9400 |
O21—C21 | 1.208 (5) | C2—H22 | 0.9500 |
O22—C21 | 1.340 (4) | C3—H31 | 0.9600 |
O22—C22 | 1.445 (5) | C4—H41 | 0.9400 |
O3—H3 | 0.9100 | C4—H42 | 0.9500 |
C1—C10 | 1.538 (5) | C6—H6 | 0.9500 |
C1—C2 | 1.520 (5) | C7—H71 | 0.9600 |
C2—C3 | 1.517 (5) | C7—H72 | 0.9400 |
C3—C4 | 1.511 (5) | C8—H8 | 0.9400 |
C4—C5 | 1.506 (5) | C9—H9 | 0.9600 |
C5—C6 | 1.326 (5) | C11—H111 | 0.9500 |
C5—C10 | 1.536 (5) | C11—H112 | 0.9400 |
C6—C7 | 1.494 (5) | C12—H121 | 0.9600 |
C7—C8 | 1.521 (5) | C12—H122 | 0.9400 |
C8—C9 | 1.539 (5) | C14—H14 | 0.9600 |
C8—C14 | 1.521 (5) | C15—H151 | 0.9400 |
C9—C11 | 1.546 (5) | C15—H152 | 0.9600 |
C9—C10 | 1.558 (5) | C16—H161 | 0.9400 |
C10—C19 | 1.549 (5) | C16—H162 | 0.9600 |
C11—C12 | 1.529 (5) | C18—H181 | 0.9500 |
C12—C13 | 1.522 (5) | C18—H182 | 0.9500 |
C13—C14 | 1.536 (5) | C18—H183 | 0.9400 |
C13—C17 | 1.517 (5) | C19—H191 | 0.9600 |
C13—C18 | 1.556 (5) | C19—H192 | 0.9400 |
C14—C15 | 1.524 (5) | C19—H193 | 0.9400 |
C15—C16 | 1.536 (5) | C20—H20 | 0.9500 |
C16—C17 | 1.519 (5) | C22—H221 | 0.9600 |
C17—C20 | 1.331 (5) | C22—H222 | 0.9500 |
C20—C21 | 1.460 (5) | C23—H231 | 0.9500 |
C22—C23 | 1.493 (6) | C23—H232 | 0.9400 |
C1—H11 | 0.9600 | C23—H233 | 0.9600 |
C1—H12 | 0.9500 | ||
O3···O21i | 2.964 (4) | H20···O3vi | 2.8900 |
O3···C22ii | 3.382 (5) | H20···C12 | 2.7300 |
O3···C23ii | 3.403 (5) | H20···H122 | 2.4000 |
O21···C16 | 2.949 (5) | H20···H183vii | 2.5700 |
O21···O3iii | 2.964 (4) | H21···C19 | 2.9000 |
O3···H221ii | 2.6800 | H21···H41 | 2.5200 |
O3···H20iv | 2.8900 | H21···H191 | 2.3500 |
O21···H3iii | 2.0700 | H21···H231ii | 2.5200 |
O21···H161 | 2.8000 | H22···H3 | 2.3700 |
O21···H162 | 2.7200 | H22···H222i | 2.2700 |
O21···H221 | 2.7000 | H31···O22iv | 2.8100 |
O21···H222 | 2.5800 | H31···H11 | 2.5400 |
O21···H233v | 2.8700 | H41···C19 | 2.9200 |
O22···H31vi | 2.8100 | H41···H21 | 2.5200 |
O22···H161vii | 2.7600 | H41···H191 | 2.3500 |
C16···O21 | 2.949 (5) | H42···C20iv | 3.0800 |
C22···O3viii | 3.382 (5) | H42···H6 | 2.2600 |
C23···O3viii | 3.403 (5) | H71···H14 | 2.3700 |
C1···H111 | 2.7800 | H72···C15 | 2.9500 |
C2···H191 | 2.8500 | H111···C1 | 2.7800 |
C4···H191 | 2.8200 | H111···H12 | 2.3100 |
C6···H9 | 2.9500 | H112···C18 | 2.7700 |
C7···H152 | 2.9300 | H112···C19 | 2.6600 |
C8···H193 | 2.9400 | H112···H181 | 2.1100 |
C8···H181 | 2.9700 | H112···H192 | 2.1700 |
C11···H181 | 2.6600 | H121···C20 | 3.0600 |
C11···H12 | 2.8600 | H121···H8vii | 2.5700 |
C11···H14 | 3.0600 | H121···H14 | 2.4000 |
C11···H192 | 2.6800 | H122···C20 | 2.9800 |
C12···H20 | 2.7300 | H122···H20 | 2.4000 |
C15···H183 | 2.6400 | H151···C18 | 2.8400 |
C15···H72 | 2.9500 | H151···C20v | 2.9500 |
C16···H183 | 2.9500 | H151···H183 | 2.2000 |
C18···H151 | 2.8400 | H152···C7 | 2.9300 |
C18···H112 | 2.7700 | H152···H12xiii | 2.5700 |
C18···H8 | 2.8200 | H161···O21 | 2.8000 |
C19···H41 | 2.9200 | H161···O22v | 2.7600 |
C19···H8 | 2.9500 | H161···C22v | 2.9400 |
C19···H21 | 2.9000 | H161···H221v | 2.5900 |
C19···H162ix | 3.0500 | H161···H233v | 2.5100 |
C19···H112 | 2.6600 | H162···O21 | 2.7200 |
C20···H122 | 2.9800 | H162···C19xiv | 3.0500 |
C20···H42vi | 3.0800 | H162···C21 | 3.0600 |
C20···H182 | 3.0100 | H162···H193xiv | 2.5600 |
C20···H121 | 3.0600 | H181···C8 | 2.9700 |
C20···H151vii | 2.9500 | H181···C11 | 2.6600 |
C21···H162 | 3.0600 | H181···H8 | 2.5000 |
C22···H161vii | 2.9400 | H181···H112 | 2.1100 |
C23···H6x | 2.9300 | H182···C20 | 3.0100 |
H3···O21i | 2.0700 | H183···C15 | 2.6400 |
H3···H22 | 2.3700 | H183···C16 | 2.9500 |
H6···C23xi | 2.9300 | H183···H20v | 2.5700 |
H6···H42 | 2.2600 | H183···H151 | 2.2000 |
H8···C18 | 2.8200 | H191···C2 | 2.8500 |
H8···C19 | 2.9500 | H191···C4 | 2.8200 |
H8···H121v | 2.5700 | H191···H21 | 2.3500 |
H8···H181 | 2.5000 | H191···H41 | 2.3500 |
H8···H193 | 2.4100 | H192···C11 | 2.6800 |
H9···C6 | 2.9500 | H192···H12 | 2.4500 |
H9···H11 | 2.2400 | H192···H112 | 2.1700 |
H9···H14 | 2.3900 | H193···C8 | 2.9400 |
H11···H9 | 2.2400 | H193···H8 | 2.4100 |
H11···H31 | 2.5400 | H193···H162ix | 2.5600 |
H11···H232iv | 2.5300 | H221···O3viii | 2.6800 |
H12···C11 | 2.8600 | H221···O21 | 2.7000 |
H12···H111 | 2.3100 | H221···H161vii | 2.5900 |
H12···H152xii | 2.5700 | H222···O21 | 2.5800 |
H12···H192 | 2.4500 | H222···H22iii | 2.2700 |
H14···C11 | 3.0600 | H231···H21viii | 2.5200 |
H14···H9 | 2.3900 | H232···H11vi | 2.5300 |
H14···H71 | 2.3700 | H233···O21vii | 2.8700 |
H14···H121 | 2.4000 | H233···H161vii | 2.5100 |
C21—O22—C22 | 117.1 (3) | H41—C4—H42 | 110.00 |
C3—O3—H3 | 109.00 | C5—C6—H6 | 117.00 |
C2—C1—C10 | 115.5 (4) | C7—C6—H6 | 117.00 |
C1—C2—C3 | 110.6 (4) | C6—C7—H71 | 108.00 |
O3—C3—C2 | 112.6 (3) | C6—C7—H72 | 109.00 |
C2—C3—C4 | 109.9 (3) | C8—C7—H71 | 109.00 |
O3—C3—C4 | 107.8 (4) | C8—C7—H72 | 109.00 |
C3—C4—C5 | 112.1 (4) | H71—C7—H72 | 109.00 |
C4—C5—C10 | 116.3 (3) | C7—C8—H8 | 109.00 |
C6—C5—C10 | 122.8 (4) | C9—C8—H8 | 109.00 |
C4—C5—C6 | 120.9 (4) | C14—C8—H8 | 109.00 |
C5—C6—C7 | 125.4 (4) | C8—C9—H9 | 106.00 |
C6—C7—C8 | 113.3 (4) | C10—C9—H9 | 106.00 |
C7—C8—C9 | 110.5 (3) | C11—C9—H9 | 106.00 |
C7—C8—C14 | 110.5 (3) | C9—C11—H111 | 108.00 |
C9—C8—C14 | 108.6 (3) | C9—C11—H112 | 108.00 |
C8—C9—C11 | 111.8 (3) | C12—C11—H111 | 108.00 |
C10—C9—C11 | 113.3 (3) | C12—C11—H112 | 108.00 |
C8—C9—C10 | 113.2 (3) | H111—C11—H112 | 110.00 |
C1—C10—C5 | 108.5 (3) | C11—C12—H121 | 109.00 |
C1—C10—C9 | 108.7 (3) | C11—C12—H122 | 109.00 |
C5—C10—C9 | 110.2 (3) | C13—C12—H121 | 109.00 |
C5—C10—C19 | 107.7 (3) | C13—C12—H122 | 110.00 |
C1—C10—C19 | 110.4 (3) | H121—C12—H122 | 109.00 |
C9—C10—C19 | 111.4 (3) | C8—C14—H14 | 106.00 |
C9—C11—C12 | 114.1 (3) | C13—C14—H14 | 106.00 |
C11—C12—C13 | 110.7 (3) | C15—C14—H14 | 106.00 |
C12—C13—C14 | 108.2 (3) | C14—C15—H151 | 111.00 |
C12—C13—C18 | 110.8 (3) | C14—C15—H152 | 110.00 |
C14—C13—C17 | 101.1 (3) | C16—C15—H151 | 112.00 |
C12—C13—C17 | 117.5 (3) | C16—C15—H152 | 111.00 |
C17—C13—C18 | 106.0 (3) | H151—C15—H152 | 109.00 |
C14—C13—C18 | 113.1 (3) | C15—C16—H161 | 110.00 |
C8—C14—C15 | 120.6 (4) | C15—C16—H162 | 110.00 |
C13—C14—C15 | 103.7 (3) | C17—C16—H161 | 111.00 |
C8—C14—C13 | 114.4 (3) | C17—C16—H162 | 111.00 |
C14—C15—C16 | 103.1 (4) | H161—C16—H162 | 109.00 |
C15—C16—C17 | 105.6 (3) | C13—C18—H181 | 109.00 |
C13—C17—C16 | 108.2 (3) | C13—C18—H182 | 109.00 |
C16—C17—C20 | 127.9 (4) | C13—C18—H183 | 109.00 |
C13—C17—C20 | 124.0 (4) | H181—C18—H182 | 110.00 |
C17—C20—C21 | 124.8 (4) | H181—C18—H183 | 110.00 |
O21—C21—O22 | 123.0 (4) | H182—C18—H183 | 110.00 |
O22—C21—C20 | 110.2 (4) | C10—C19—H191 | 109.00 |
O21—C21—C20 | 126.8 (4) | C10—C19—H192 | 109.00 |
O22—C22—C23 | 106.9 (4) | C10—C19—H193 | 109.00 |
C2—C1—H11 | 108.00 | H191—C19—H192 | 110.00 |
C2—C1—H12 | 108.00 | H191—C19—H193 | 110.00 |
C10—C1—H11 | 108.00 | H192—C19—H193 | 111.00 |
C10—C1—H12 | 108.00 | C17—C20—H20 | 117.00 |
H11—C1—H12 | 109.00 | C21—C20—H20 | 118.00 |
C1—C2—H21 | 109.00 | O22—C22—H221 | 110.00 |
C1—C2—H22 | 109.00 | O22—C22—H222 | 110.00 |
C3—C2—H21 | 109.00 | C23—C22—H221 | 110.00 |
C3—C2—H22 | 109.00 | C23—C22—H222 | 110.00 |
H21—C2—H22 | 110.00 | H221—C22—H222 | 109.00 |
O3—C3—H31 | 109.00 | C22—C23—H231 | 110.00 |
C2—C3—H31 | 109.00 | C22—C23—H232 | 109.00 |
C4—C3—H31 | 109.00 | C22—C23—H233 | 109.00 |
C3—C4—H41 | 108.00 | H231—C23—H232 | 111.00 |
C3—C4—H42 | 108.00 | H231—C23—H233 | 109.00 |
C5—C4—H41 | 109.00 | H232—C23—H233 | 109.00 |
C5—C4—H42 | 109.00 | ||
C22—O22—C21—O21 | −2.6 (5) | C8—C9—C10—C1 | −162.4 (3) |
C22—O22—C21—C20 | 177.0 (3) | C10—C9—C11—C12 | −179.4 (3) |
C21—O22—C22—C23 | −173.6 (4) | C8—C9—C11—C12 | 51.3 (4) |
C2—C1—C10—C19 | −70.2 (4) | C11—C9—C10—C1 | 69.0 (4) |
C2—C1—C10—C9 | 167.4 (3) | C11—C9—C10—C5 | −172.3 (3) |
C10—C1—C2—C3 | −55.5 (5) | C8—C9—C10—C19 | 75.9 (4) |
C2—C1—C10—C5 | 47.6 (4) | C11—C9—C10—C19 | −52.8 (4) |
C1—C2—C3—O3 | 177.7 (4) | C9—C11—C12—C13 | −53.7 (4) |
C1—C2—C3—C4 | 57.5 (5) | C11—C12—C13—C17 | 169.3 (3) |
C2—C3—C4—C5 | −56.3 (4) | C11—C12—C13—C14 | 55.8 (4) |
O3—C3—C4—C5 | −179.3 (3) | C11—C12—C13—C18 | −68.8 (4) |
C3—C4—C5—C6 | −127.2 (4) | C18—C13—C14—C8 | 62.4 (4) |
C3—C4—C5—C10 | 52.4 (4) | C18—C13—C14—C15 | −70.9 (4) |
C4—C5—C10—C19 | 73.6 (4) | C12—C13—C14—C8 | −60.8 (4) |
C6—C5—C10—C1 | 133.7 (4) | C12—C13—C14—C15 | 165.9 (3) |
C4—C5—C6—C7 | 179.5 (4) | C17—C13—C14—C8 | 175.2 (3) |
C10—C5—C6—C7 | −0.1 (6) | C17—C13—C14—C15 | 41.9 (4) |
C4—C5—C10—C1 | −45.9 (4) | C18—C13—C17—C20 | −90.9 (4) |
C4—C5—C10—C9 | −164.8 (3) | C12—C13—C17—C20 | 33.5 (5) |
C6—C5—C10—C9 | 14.8 (5) | C14—C13—C17—C16 | −28.2 (4) |
C6—C5—C10—C19 | −106.8 (4) | C12—C13—C17—C16 | −145.7 (3) |
C5—C6—C7—C8 | 14.0 (6) | C18—C13—C17—C16 | 89.9 (4) |
C6—C7—C8—C14 | −161.9 (4) | C14—C13—C17—C20 | 151.0 (4) |
C6—C7—C8—C9 | −41.6 (5) | C13—C14—C15—C16 | −39.9 (4) |
C7—C8—C9—C11 | −172.3 (3) | C8—C14—C15—C16 | −169.6 (3) |
C14—C8—C9—C10 | 179.7 (3) | C14—C15—C16—C17 | 21.9 (4) |
C7—C8—C9—C10 | 58.3 (4) | C15—C16—C17—C13 | 4.3 (4) |
C7—C8—C14—C13 | 179.3 (3) | C15—C16—C17—C20 | −174.9 (4) |
C7—C8—C14—C15 | −56.0 (4) | C16—C17—C20—C21 | −1.9 (6) |
C14—C8—C9—C11 | −50.9 (4) | C13—C17—C20—C21 | 179.1 (4) |
C9—C8—C14—C15 | −177.3 (3) | C17—C20—C21—O22 | 178.5 (4) |
C9—C8—C14—C13 | 57.9 (4) | C17—C20—C21—O21 | −1.8 (6) |
C8—C9—C10—C5 | −43.6 (4) |
Symmetry codes: (i) x+1, y+1, z+1; (ii) x+2, y+1, z+1; (iii) x−1, y−1, z−1; (iv) x+1, y, z+1; (v) x+1, y, z; (vi) x−1, y, z−1; (vii) x−1, y, z; (viii) x−2, y−1, z−1; (ix) x+1, y+1, z; (x) x−2, y, z−1; (xi) x+2, y, z+1; (xii) x, y+1, z; (xiii) x, y−1, z; (xiv) x−1, y−1, z. |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O21i | 0.91 | 2.07 | 2.964 (4) | 167 |
Symmetry code: (i) x+1, y+1, z+1. |
Experimental details
Crystal data | |
Chemical formula | C23H34O3 |
Mr | 358.50 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 295 |
a, b, c (Å) | 6.3179 (17), 8.0901 (16), 10.880 (2) |
α, β, γ (°) | 73.8 (2), 100.311 (19), 109.285 (16) |
V (Å3) | 501.7 (5) |
Z | 1 |
Radiation type | Mo Kα |
µ (mm−1) | 0.08 |
Crystal size (mm) | 0.40 × 0.35 × 0.20 |
Data collection | |
Diffractometer | Rigaku AFC-7R diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2086, 1756, 1506 |
Rint | 0.033 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.041, 0.111, 1.04 |
No. of reflections | 1756 |
No. of parameters | 235 |
No. of restraints | 3 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.15, −0.19 |
Computer programs: MSC/AFC7 Diffractometer Control Software for Windows (Molecular Structure Corporation, 1999), MSC/AFC7 Diffractometer Control Software for Windows, TEXSAN for Windows (Molecular Structure Corporation, 2001), TEXSAN for Windows and SHELXL97 (Sheldrick, 1997), ORTEP-3 (Farrugia, 1997), TEXSAN for Windows and PLATON (Spek, 2003).
O3—C3 | 1.436 (4) | C5—C6 | 1.326 (5) |
O21—C21 | 1.208 (5) | C17—C20 | 1.331 (5) |
O22—C21 | 1.340 (4) | C20—C21 | 1.460 (5) |
O22—C22 | 1.445 (5) | ||
C21—O22—C22 | 117.1 (3) | O22—C21—C20 | 110.2 (4) |
O3—C3—C2 | 112.6 (3) | O21—C21—C20 | 126.8 (4) |
O3—C3—C4 | 107.8 (4) | O22—C22—C23 | 106.9 (4) |
O21—C21—O22 | 123.0 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O21i | 0.91 | 2.07 | 2.964 (4) | 167 |
Symmetry code: (i) x+1, y+1, z+1. |
Recent research suggests that steroids such as ergosterol and fusidic acid display antitubercular activity (Ruggutt & Ruggutt, 2001). In fact, the minimum inhibitory concentration (MIC) for these steroids is comparable to a number of clinically used anti-TB drugs. This, as well as the structural similarity of the title compound, (II), with fusidic acid and ergosterol has prompted us to consider conjugation of this compound with a number of well known anti-TB agents (Ballell et al., 2005). Our aim is to increase the lipophilicity of the parent drug by attaching a steroid moiety which could have anti-TB activity in its own right. As part of this project, compound (II) was prepared from the commercially available ketone, dehydroandrosterone (I) (Verma et al., 2004), by the Wittig–Horner reaction (Wicha et al., 1977), and was recrystallized from methanol.
Compound (II) crystallizes in the space group P1 with one molecule in the unit cell. The fused tetracyclic ring system adopts the expected conformations for the all-transA/B/C/D junctions. The six-membered rings A and C adopt normal chair conformations. As previously observed in related structures (Thamotharan et al., 2004; Verma et al., 2004), the hydroxy group on C3 does not perturb the structure of ring A. The C5═C6 bond length of 1.326 (5) Å confirms the presence of the double bond in this position and imposes an 8β,9α-half-chair conformation on ring B. Ring D adopts the 14α-envelope conformation previously observed in the dehydroandrosterone parent (Verma et al., 2004); this conformation minimizes steric interactions with the angular C18 methyl group (Fuchs, 1978).
The C17═C20 bond length of 1.331 (5) Å confirms the presence of the double bond in this position. The substitutents on this bond adopt the thermodynamically favoured E configuration which, again, minimizes interactions with the angular methyl group. The C20—C21 bond length of 1.460 (5) Å suggests partial double-bond character, with the ester group adopting an s-trans configuration. The molecules in the crystal structure are linked through intermolecular C11(n) (Bernstein et al., 1995) O—H···O hydrogen bonds between the O3 hydroxy proton and the O21 carbonyl O atom (Table 2), forming infinite chains along the body diagonal of the unit cell.
The 1H and 13C NMR spectra of the compound were fully assigned using two-dimensional gCOSY, gHSQC and gHMBC methods. The lowfield 13C chemical shifts of the C17 (176.15 p.p.m.) and C21 (167.45 p.p.m.) C atoms were confirmed by the presence of unambiguous cross peaks in the gHMBC spectrum linking (i) the 176.15 p.p.m. resonance with the H18 and H16 resonances and (ii) the 167.45 p.p.m. resonance with the H20 and H22 resonances. The 13C chemical shift of C20 (108.62 p.p.m.) was confirmed by direct correlation of the C20 and H20 resonances in the gHSQC matrix. The 13C chemical shifts of the C17, C21 and C20 atoms can be compared with those previously observed for 13C nuclei in the isolated D-ring analogue methyl 2-methylenecyclopentane acetate (Molander & Harris, 1997), i.e. 169.51, 167.31 and 111.18 p.p.m., respectively.