In the title compound, C
29H
42O
4·H
2O, cyclohexane rings
A and
B are in the sofa conformation, ring
C is in a chair conformation and the five-membered ring
D is in an envelope conformation. The structure is stabilized by inter- and intramolecular C-H
O and O-H
O hydrogen bonds.
Supporting information
CCDC reference: 147700
24(R)-Hydroxycoprastan-3-one, obtained from lithocholic acid on usual acetylation with acetic anhydride and pyridine, afforded 24(R)-acetoxycoprastan-3-one. This, on bromination with bromine and acetic acid and subsequent dehydrobromination (Wilds & Djerassi, 1946), afforded 24(R)-acetoxycholesta-1,4-dien-3-one. Further bromination using N-bromosuccinimide and dehydrobromination (Kaufmann et al., 1950) of the resulting bromide gave 24-(R)-acetoxycholesta-1,4,6-trien-3-one. Epoxidation of the trienone using 30% aqueous hydrodgen peroxide under alkaline conditions yielded the title compound. Single crystals were obtained by slow evaporation from a solution in methanol.
Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms, 1996); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); software used to prepare material for publication: SHELXL and PARST (Nardelli, 1983).
1a,2a-Epoxy-24(
R)-acyloxycholesta-4,6-dien-3-one hydrate
top
Crystal data top
C29H42O4·H2O | F(000) = 512 |
Mr = 472.64 | Dx = 1.206 Mg m−3 |
Monoclinic, P21 | Cu Kα radiation, λ = 1.54180 Å |
a = 10.642 (3) Å | Cell parameters from 25 reflections |
b = 11.719 (2) Å | θ = 10–27° |
c = 10.977 (3) Å | µ = 0.64 mm−1 |
β = 108.04 (2)° | T = 293 K |
V = 1301.7 (6) Å3 | Rectangle, colourless |
Z = 2 | 0.20 × 0.15 × 0.10 mm |
Data collection top
Enraf-Nonius CAD-4 diffractometer | Rint = 0.016 |
Radiation source: fine-focus sealed tube | θmax = 74.9°, θmin = 4.2° |
Graphite monochromator | h = 0→13 |
ω/2θ scans | k = 0→13 |
2848 measured reflections | l = −13→13 |
2712 independent reflections | 3 standard reflections every 120 min |
2262 reflections with I > 2σ(I) | intensity decay: <3% |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full with fixed elements per cycle | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.056 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.162 | Calculated w = 1/[σ2(Fo2) + (0.095P)2 + 0.2101P] where P = (Fo2 + 2Fc2)/3 |
S = 1.12 | (Δ/σ)max = 0.010 |
2712 reflections | Δρmax = 0.27 e Å−3 |
322 parameters | Δρmin = −0.55 e Å−3 |
1 restraint | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0091 (15) |
Crystal data top
C29H42O4·H2O | V = 1301.7 (6) Å3 |
Mr = 472.64 | Z = 2 |
Monoclinic, P21 | Cu Kα radiation |
a = 10.642 (3) Å | µ = 0.64 mm−1 |
b = 11.719 (2) Å | T = 293 K |
c = 10.977 (3) Å | 0.20 × 0.15 × 0.10 mm |
β = 108.04 (2)° | |
Data collection top
Enraf-Nonius CAD-4 diffractometer | Rint = 0.016 |
2848 measured reflections | 3 standard reflections every 120 min |
2712 independent reflections | intensity decay: <3% |
2262 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.056 | 1 restraint |
wR(F2) = 0.162 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.12 | Δρmax = 0.27 e Å−3 |
2712 reflections | Δρmin = −0.55 e Å−3 |
322 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 | −0.0854 (3) | 1.8844 (3) | 0.0756 (3) | 0.0670 (9) | |
O2 | −0.1021 (3) | 1.5957 (3) | 0.1111 (3) | 0.0555 (7) | |
O3 | 0.3554 (2) | 0.8864 (3) | 0.9399 (2) | 0.0453 (6) | |
O4 | 0.1624 (3) | 0.8141 (3) | 0.9464 (3) | 0.0678 (9) | |
C1 | 0.0359 (4) | 1.5926 (4) | 0.1243 (3) | 0.0478 (9) | |
H1 | 0.0610 | 1.5387 | 0.0677 | 0.057* | |
C2 | −0.0438 (4) | 1.6889 (4) | 0.0602 (4) | 0.0506 (9) | |
H2 | −0.0648 | 1.6938 | −0.0331 | 0.061* | |
C3 | −0.0375 (4) | 1.7967 (4) | 0.1312 (4) | 0.0477 (9) | |
C4 | 0.0241 (4) | 1.7899 (4) | 0.2703 (4) | 0.0494 (9) | |
H4 | 0.0130 | 1.8512 | 0.3199 | 0.059* | |
C5 | 0.0952 (4) | 1.7006 (4) | 0.3300 (3) | 0.0433 (8) | |
C6 | 0.1415 (5) | 1.6968 (4) | 0.4687 (4) | 0.0559 (11) | |
H6 | 0.1273 | 1.7602 | 0.5137 | 0.067* | |
C7 | 0.2039 (5) | 1.6063 (4) | 0.5356 (4) | 0.0537 (10) | |
H7 | 0.2307 | 1.6095 | 0.6246 | 0.064* | |
C8 | 0.2314 (4) | 1.5016 (4) | 0.4727 (3) | 0.0438 (8) | |
H8 | 0.3211 | 1.5083 | 0.4668 | 0.053* | |
C9 | 0.1357 (4) | 1.4910 (3) | 0.3352 (3) | 0.0390 (8) | |
H9 | 0.0470 | 1.4828 | 0.3434 | 0.047* | |
C10 | 0.1339 (3) | 1.6025 (4) | 0.2590 (3) | 0.0410 (8) | |
C11 | 0.1616 (5) | 1.3822 (4) | 0.2691 (3) | 0.0524 (10) | |
H11A | 0.0927 | 1.3740 | 0.1876 | 0.063* | |
H11B | 0.2451 | 1.3902 | 0.2517 | 0.063* | |
C12 | 0.1660 (5) | 1.2753 (4) | 0.3478 (3) | 0.0519 (10) | |
H12A | 0.1909 | 1.2111 | 0.3043 | 0.062* | |
H12B | 0.0783 | 1.2602 | 0.3533 | 0.062* | |
C13 | 0.2639 (4) | 1.2843 (3) | 0.4842 (3) | 0.0408 (8) | |
C14 | 0.2250 (4) | 1.3914 (4) | 0.5447 (3) | 0.0424 (8) | |
H14 | 0.1320 | 1.3813 | 0.5394 | 0.051* | |
C15 | 0.3035 (5) | 1.3823 (4) | 0.6861 (4) | 0.0582 (11) | |
H15A | 0.3913 | 1.4142 | 0.7027 | 0.070* | |
H15B | 0.2589 | 1.4218 | 0.7386 | 0.070* | |
C16 | 0.3102 (5) | 1.2547 (4) | 0.7126 (3) | 0.0537 (11) | |
H16A | 0.2593 | 1.2358 | 0.7695 | 0.064* | |
H16B | 0.4011 | 1.2314 | 0.7531 | 0.064* | |
C17 | 0.2524 (4) | 1.1927 (4) | 0.5825 (3) | 0.0436 (8) | |
H17 | 0.1579 | 1.1820 | 0.5698 | 0.052* | |
C18 | 0.4057 (4) | 1.2893 (5) | 0.4795 (5) | 0.0609 (12) | |
H18A | 0.4243 | 1.2217 | 0.4389 | 0.091* | |
H18B | 0.4656 | 1.2942 | 0.5650 | 0.091* | |
H18C | 0.4162 | 1.3552 | 0.4315 | 0.091* | |
C19 | 0.2694 (4) | 1.6302 (4) | 0.2444 (5) | 0.0599 (12) | |
H19A | 0.2957 | 1.5696 | 0.1987 | 0.090* | |
H19B | 0.3334 | 1.6381 | 0.3276 | 0.090* | |
H19C | 0.2639 | 1.7003 | 0.1977 | 0.090* | |
C20 | 0.3119 (4) | 1.0738 (4) | 0.5832 (3) | 0.0463 (9) | |
H20 | 0.4079 | 1.0833 | 0.6065 | 0.056* | |
C21 | 0.2671 (6) | 1.0148 (5) | 0.4531 (4) | 0.0696 (14) | |
H21A | 0.1729 | 1.0209 | 0.4173 | 0.104* | |
H21B | 0.2918 | 0.9357 | 0.4634 | 0.104* | |
H21C | 0.3085 | 1.0505 | 0.3967 | 0.104* | |
C22 | 0.2845 (4) | 0.9979 (4) | 0.6854 (4) | 0.0512 (10) | |
H22A | 0.2848 | 1.0450 | 0.7582 | 0.061* | |
H22B | 0.1969 | 0.9652 | 0.6509 | 0.061* | |
C23 | 0.3830 (4) | 0.9025 (4) | 0.7313 (4) | 0.0506 (10) | |
H23A | 0.4695 | 0.9357 | 0.7710 | 0.061* | |
H23B | 0.3875 | 0.8592 | 0.6574 | 0.061* | |
C24 | 0.3533 (4) | 0.8201 (4) | 0.8264 (3) | 0.0431 (9) | |
H24 | 0.2646 | 0.7883 | 0.7882 | 0.052* | |
C25 | 0.4510 (4) | 0.7234 (4) | 0.8664 (4) | 0.0512 (10) | |
H25 | 0.4499 | 0.6826 | 0.7881 | 0.061* | |
C26 | 0.4119 (5) | 0.6376 (5) | 0.9527 (5) | 0.0665 (12) | |
H26A | 0.4240 | 0.6712 | 1.0353 | 0.100* | |
H26B | 0.4663 | 0.5707 | 0.9621 | 0.100* | |
H26C | 0.3208 | 0.6167 | 0.9150 | 0.100* | |
C27 | 0.5931 (4) | 0.7633 (5) | 0.9299 (5) | 0.0678 (14) | |
H27A | 0.6240 | 0.8032 | 0.8683 | 0.102* | |
H27B | 0.6486 | 0.6984 | 0.9615 | 0.102* | |
H27C | 0.5958 | 0.8135 | 0.9998 | 0.102* | |
C28 | 0.2567 (4) | 0.8735 (4) | 0.9903 (4) | 0.0469 (9) | |
C29 | 0.2819 (5) | 0.9406 (5) | 1.1110 (4) | 0.0606 (11) | |
H29A | 0.2001 | 0.9525 | 1.1289 | 0.091* | |
H29B | 0.3197 | 1.0131 | 1.1011 | 0.091* | |
H29C | 0.3421 | 0.8996 | 1.1805 | 0.091* | |
O1W | 0.0684 (19) | 0.5921 (16) | 0.7944 (15) | 0.298 (8) | |
H1W | 0.095 (5) | 0.658 (5) | 0.846 (5) | 0.126 (14)* | |
H2W | 0.082 (5) | 0.520 (5) | 0.850 (5) | 0.125 (14)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.083 (2) | 0.059 (2) | 0.0609 (18) | 0.0183 (19) | 0.0247 (16) | 0.0202 (17) |
O2 | 0.0548 (16) | 0.0564 (19) | 0.0486 (14) | −0.0057 (14) | 0.0061 (12) | 0.0047 (14) |
O3 | 0.0443 (13) | 0.0523 (16) | 0.0420 (12) | −0.0032 (13) | 0.0172 (10) | 0.0013 (12) |
O4 | 0.0548 (17) | 0.075 (2) | 0.081 (2) | −0.0157 (17) | 0.0318 (16) | −0.0098 (19) |
C1 | 0.057 (2) | 0.052 (2) | 0.0351 (17) | 0.0089 (19) | 0.0152 (16) | 0.0070 (17) |
C2 | 0.056 (2) | 0.055 (3) | 0.0396 (17) | 0.0035 (19) | 0.0134 (16) | 0.0063 (19) |
C3 | 0.0464 (19) | 0.048 (2) | 0.051 (2) | 0.0047 (18) | 0.0191 (16) | 0.0085 (19) |
C4 | 0.053 (2) | 0.046 (2) | 0.050 (2) | 0.0008 (19) | 0.0175 (16) | −0.0020 (18) |
C5 | 0.0432 (18) | 0.045 (2) | 0.0396 (17) | −0.0037 (16) | 0.0096 (14) | −0.0005 (16) |
C6 | 0.068 (3) | 0.050 (3) | 0.0430 (19) | −0.001 (2) | 0.0083 (18) | −0.0088 (19) |
C7 | 0.067 (3) | 0.049 (3) | 0.0355 (18) | −0.003 (2) | 0.0028 (17) | −0.0022 (18) |
C8 | 0.0413 (18) | 0.048 (2) | 0.0377 (16) | −0.0021 (17) | 0.0066 (14) | 0.0011 (17) |
C9 | 0.0404 (17) | 0.045 (2) | 0.0319 (15) | 0.0024 (15) | 0.0111 (13) | 0.0018 (15) |
C10 | 0.0414 (17) | 0.046 (2) | 0.0375 (16) | 0.0006 (16) | 0.0146 (14) | 0.0039 (16) |
C11 | 0.073 (3) | 0.052 (3) | 0.0299 (16) | 0.005 (2) | 0.0139 (16) | 0.0009 (18) |
C12 | 0.071 (3) | 0.049 (3) | 0.0322 (17) | 0.005 (2) | 0.0112 (17) | 0.0005 (16) |
C13 | 0.0447 (18) | 0.047 (2) | 0.0314 (16) | 0.0037 (17) | 0.0123 (14) | 0.0033 (15) |
C14 | 0.0454 (18) | 0.049 (2) | 0.0318 (16) | −0.0012 (17) | 0.0098 (14) | 0.0019 (16) |
C15 | 0.074 (3) | 0.056 (3) | 0.0367 (19) | 0.000 (2) | 0.0055 (18) | 0.0004 (19) |
C16 | 0.068 (3) | 0.061 (3) | 0.0293 (17) | 0.008 (2) | 0.0111 (16) | 0.0047 (17) |
C17 | 0.0399 (18) | 0.055 (2) | 0.0373 (16) | 0.0033 (17) | 0.0135 (14) | 0.0069 (17) |
C18 | 0.057 (2) | 0.066 (3) | 0.070 (3) | 0.011 (2) | 0.034 (2) | 0.019 (2) |
C19 | 0.052 (2) | 0.062 (3) | 0.075 (3) | 0.002 (2) | 0.033 (2) | 0.021 (2) |
C20 | 0.0468 (19) | 0.055 (3) | 0.0399 (18) | 0.0019 (17) | 0.0170 (15) | 0.0068 (17) |
C21 | 0.102 (4) | 0.057 (3) | 0.047 (2) | 0.009 (3) | 0.019 (2) | 0.004 (2) |
C22 | 0.051 (2) | 0.057 (3) | 0.050 (2) | 0.007 (2) | 0.0226 (17) | 0.013 (2) |
C23 | 0.0486 (19) | 0.061 (3) | 0.0473 (19) | 0.0073 (19) | 0.0224 (16) | 0.0138 (19) |
C24 | 0.0443 (18) | 0.049 (2) | 0.0371 (17) | −0.0001 (16) | 0.0143 (14) | 0.0009 (16) |
C25 | 0.057 (2) | 0.054 (3) | 0.0428 (18) | 0.007 (2) | 0.0154 (16) | 0.0069 (18) |
C26 | 0.078 (3) | 0.054 (3) | 0.069 (3) | 0.011 (2) | 0.025 (2) | 0.016 (2) |
C27 | 0.053 (2) | 0.082 (4) | 0.066 (3) | 0.014 (2) | 0.015 (2) | 0.024 (3) |
C28 | 0.0479 (19) | 0.051 (2) | 0.0458 (18) | 0.0047 (19) | 0.0208 (15) | 0.0089 (18) |
C29 | 0.076 (3) | 0.061 (3) | 0.051 (2) | 0.006 (2) | 0.029 (2) | 0.004 (2) |
O1W | 0.349 (18) | 0.22 (2) | 0.308 (19) | 0.027 (17) | 0.074 (15) | −0.006 (18) |
Geometric parameters (Å, º) top
O1—C3 | 1.223 (5) | C16—C17 | 1.549 (5) |
O2—C1 | 1.431 (5) | C16—H16A | 0.9700 |
O2—C2 | 1.451 (5) | C16—H16B | 0.9700 |
O3—C28 | 1.339 (4) | C17—C20 | 1.530 (6) |
O3—C24 | 1.462 (4) | C17—H17 | 0.9800 |
O4—C28 | 1.194 (5) | C18—H18A | 0.9600 |
C1—C2 | 1.456 (6) | C18—H18B | 0.9600 |
C1—C10 | 1.526 (5) | C18—H18C | 0.9600 |
C1—H1 | 0.9800 | C19—H19A | 0.9600 |
C2—C3 | 1.475 (6) | C19—H19B | 0.9600 |
C2—H2 | 0.9800 | C19—H19C | 0.9600 |
C3—C4 | 1.465 (6) | C20—C21 | 1.524 (6) |
C4—C5 | 1.339 (6) | C20—C22 | 1.529 (5) |
C4—H4 | 0.9300 | C20—H20 | 0.9800 |
C5—C6 | 1.449 (5) | C21—H21A | 0.9600 |
C5—C10 | 1.515 (6) | C21—H21B | 0.9600 |
C6—C7 | 1.342 (6) | C21—H21C | 0.9600 |
C6—H6 | 0.9300 | C22—C23 | 1.509 (6) |
C7—C8 | 1.481 (6) | C22—H22A | 0.9700 |
C7—H7 | 0.9300 | C22—H22B | 0.9700 |
C8—C14 | 1.527 (6) | C23—C24 | 1.525 (5) |
C8—C9 | 1.543 (5) | C23—H23A | 0.9700 |
C8—H8 | 0.9800 | C23—H23B | 0.9700 |
C9—C11 | 1.533 (6) | C24—C25 | 1.509 (6) |
C9—C10 | 1.548 (5) | C24—H24 | 0.9800 |
C9—H9 | 0.9800 | C25—C27 | 1.529 (6) |
C10—C19 | 1.535 (5) | C25—C26 | 1.526 (6) |
C11—C12 | 1.515 (6) | C25—H25 | 0.9800 |
C11—H11A | 0.9700 | C26—H26A | 0.9600 |
C11—H11B | 0.9700 | C26—H26B | 0.9600 |
C12—C13 | 1.541 (5) | C26—H26C | 0.9600 |
C12—H12A | 0.9700 | C27—H27A | 0.9600 |
C12—H12B | 0.9700 | C27—H27B | 0.9600 |
C13—C18 | 1.527 (5) | C27—H27C | 0.9600 |
C13—C14 | 1.535 (6) | C28—C29 | 1.492 (6) |
C13—C17 | 1.554 (5) | C29—H29A | 0.9600 |
C14—C15 | 1.522 (5) | C29—H29B | 0.9600 |
C14—H14 | 0.9800 | C29—H29C | 0.9600 |
C15—C16 | 1.522 (7) | O1W—H1W | 0.94 (5) |
C15—H15A | 0.9700 | O1W—H2W | 1.03 (5) |
C15—H15B | 0.9700 | | |
| | | |
C1—O2—C2 | 60.7 (3) | C15—C16—H16B | 110.2 |
C28—O3—C24 | 119.0 (3) | C17—C16—H16B | 110.2 |
O2—C1—C2 | 60.3 (3) | H16A—C16—H16B | 108.5 |
O2—C1—C10 | 117.9 (3) | C20—C17—C16 | 112.2 (3) |
C2—C1—C10 | 122.0 (4) | C20—C17—C13 | 120.7 (3) |
O2—C1—H1 | 115.2 | C16—C17—C13 | 102.9 (3) |
C2—C1—H1 | 115.2 | C20—C17—H17 | 106.8 |
C10—C1—H1 | 115.2 | C16—C17—H17 | 106.8 |
O2—C2—C1 | 59.0 (3) | C13—C17—H17 | 106.8 |
O2—C2—C3 | 113.3 (3) | C13—C18—H18A | 109.5 |
C1—C2—C3 | 118.9 (3) | C13—C18—H18B | 109.5 |
O2—C2—H2 | 117.4 | H18A—C18—H18B | 109.5 |
C1—C2—H2 | 117.4 | C13—C18—H18C | 109.5 |
C3—C2—H2 | 117.4 | H18A—C18—H18C | 109.5 |
O1—C3—C4 | 123.3 (4) | H18B—C18—H18C | 109.5 |
O1—C3—C2 | 120.8 (4) | C10—C19—H19A | 109.5 |
C4—C3—C2 | 115.9 (4) | C10—C19—H19B | 109.5 |
C5—C4—C3 | 123.7 (4) | H19A—C19—H19B | 109.5 |
C5—C4—H4 | 118.1 | C10—C19—H19C | 109.5 |
C3—C4—H4 | 118.1 | H19A—C19—H19C | 109.5 |
C4—C5—C6 | 119.7 (4) | H19B—C19—H19C | 109.5 |
C4—C5—C10 | 122.9 (3) | C21—C20—C17 | 113.6 (3) |
C6—C5—C10 | 117.3 (4) | C21—C20—C22 | 110.4 (4) |
C7—C6—C5 | 123.3 (4) | C17—C20—C22 | 111.1 (3) |
C7—C6—H6 | 118.4 | C21—C20—H20 | 107.1 |
C5—C6—H6 | 118.4 | C17—C20—H20 | 107.1 |
C6—C7—C8 | 122.3 (3) | C22—C20—H20 | 107.1 |
C6—C7—H7 | 118.8 | C20—C21—H21A | 109.5 |
C8—C7—H7 | 118.8 | C20—C21—H21B | 109.5 |
C7—C8—C14 | 114.4 (3) | H21A—C21—H21B | 109.5 |
C7—C8—C9 | 110.9 (3) | C20—C21—H21C | 109.5 |
C14—C8—C9 | 108.4 (3) | H21A—C21—H21C | 109.5 |
C7—C8—H8 | 107.6 | H21B—C21—H21C | 109.5 |
C14—C8—H8 | 107.6 | C23—C22—C20 | 113.9 (3) |
C9—C8—H8 | 107.6 | C23—C22—H22A | 108.8 |
C11—C9—C8 | 111.6 (3) | C20—C22—H22A | 108.8 |
C11—C9—C10 | 114.8 (3) | C23—C22—H22B | 108.8 |
C8—C9—C10 | 110.8 (3) | C20—C22—H22B | 108.8 |
C11—C9—H9 | 106.3 | H22A—C22—H22B | 107.7 |
C8—C9—H9 | 106.3 | C22—C23—C24 | 115.3 (3) |
C10—C9—H9 | 106.3 | C22—C23—H23A | 108.4 |
C5—C10—C1 | 110.1 (3) | C24—C23—H23A | 108.4 |
C5—C10—C19 | 107.8 (4) | C22—C23—H23B | 108.4 |
C1—C10—C19 | 107.3 (3) | C24—C23—H23B | 108.4 |
C5—C10—C9 | 108.8 (3) | H23A—C23—H23B | 107.5 |
C1—C10—C9 | 110.4 (3) | O3—C24—C25 | 108.9 (3) |
C19—C10—C9 | 112.4 (3) | O3—C24—C23 | 107.2 (3) |
C12—C11—C9 | 113.4 (3) | C25—C24—C23 | 113.8 (3) |
C12—C11—H11A | 108.9 | O3—C24—H24 | 109.0 |
C9—C11—H11A | 108.9 | C25—C24—H24 | 109.0 |
C12—C11—H11B | 108.9 | C23—C24—H24 | 109.0 |
C9—C11—H11B | 108.9 | C24—C25—C27 | 113.5 (4) |
H11A—C11—H11B | 107.7 | C24—C25—C26 | 112.3 (4) |
C11—C12—C13 | 112.9 (4) | C27—C25—C26 | 109.9 (4) |
C11—C12—H12A | 109.0 | C24—C25—H25 | 106.9 |
C13—C12—H12A | 109.0 | C27—C25—H25 | 106.9 |
C11—C12—H12B | 109.0 | C26—C25—H25 | 106.9 |
C13—C12—H12B | 109.0 | C25—C26—H26A | 109.5 |
H12A—C12—H12B | 107.8 | C25—C26—H26B | 109.5 |
C18—C13—C14 | 112.7 (4) | H26A—C26—H26B | 109.5 |
C18—C13—C12 | 110.3 (3) | C25—C26—H26C | 109.5 |
C14—C13—C12 | 106.6 (3) | H26A—C26—H26C | 109.5 |
C18—C13—C17 | 110.0 (3) | H26B—C26—H26C | 109.5 |
C14—C13—C17 | 100.1 (3) | C25—C27—H27A | 109.5 |
C12—C13—C17 | 116.9 (3) | C25—C27—H27B | 109.5 |
C15—C14—C8 | 119.2 (3) | H27A—C27—H27B | 109.5 |
C15—C14—C13 | 104.3 (3) | C25—C27—H27C | 109.5 |
C8—C14—C13 | 114.0 (3) | H27A—C27—H27C | 109.5 |
C15—C14—H14 | 106.1 | H27B—C27—H27C | 109.5 |
C8—C14—H14 | 106.1 | O4—C28—O3 | 124.6 (4) |
C13—C14—H14 | 106.1 | O4—C28—C29 | 124.3 (4) |
C16—C15—C14 | 104.0 (3) | O3—C28—C29 | 111.0 (4) |
C16—C15—H15A | 111.0 | C28—C29—H29A | 109.5 |
C14—C15—H15A | 111.0 | C28—C29—H29B | 109.5 |
C16—C15—H15B | 111.0 | H29A—C29—H29B | 109.5 |
C14—C15—H15B | 111.0 | C28—C29—H29C | 109.5 |
H15A—C15—H15B | 109.0 | H29A—C29—H29C | 109.5 |
C15—C16—C17 | 107.6 (3) | H29B—C29—H29C | 109.5 |
C15—C16—H16A | 110.2 | H1W—O1W—H2W | 111 (6) |
C17—C16—H16A | 110.2 | | |
| | | |
C2—O2—C1—C10 | 112.9 (4) | C9—C11—C12—C13 | −53.3 (5) |
C1—O2—C2—C3 | −110.8 (4) | C11—C12—C13—C18 | −67.5 (5) |
C10—C1—C2—O2 | −106.2 (4) | C11—C12—C13—C14 | 55.1 (4) |
O2—C1—C2—C3 | 101.3 (4) | C11—C12—C13—C17 | 165.9 (3) |
C10—C1—C2—C3 | −4.9 (6) | C7—C8—C14—C15 | −51.6 (5) |
O2—C2—C3—O1 | −125.7 (4) | C9—C8—C14—C15 | −175.9 (3) |
C1—C2—C3—O1 | 168.1 (4) | C7—C8—C14—C13 | −175.6 (3) |
O2—C2—C3—C4 | 52.0 (5) | C9—C8—C14—C13 | 60.0 (4) |
C1—C2—C3—C4 | −14.3 (6) | C18—C13—C14—C15 | −70.8 (4) |
O1—C3—C4—C5 | −168.8 (4) | C12—C13—C14—C15 | 168.1 (3) |
C2—C3—C4—C5 | 13.6 (6) | C17—C13—C14—C15 | 45.9 (4) |
C3—C4—C5—C6 | −174.0 (4) | C18—C13—C14—C8 | 60.9 (4) |
C3—C4—C5—C10 | 7.6 (6) | C12—C13—C14—C8 | −60.2 (4) |
C4—C5—C6—C7 | 174.4 (4) | C17—C13—C14—C8 | 177.6 (3) |
C10—C5—C6—C7 | −7.2 (6) | C8—C14—C15—C16 | −162.1 (4) |
C5—C6—C7—C8 | 0.2 (7) | C13—C14—C15—C16 | −33.5 (4) |
C6—C7—C8—C14 | −145.8 (4) | C14—C15—C16—C17 | 7.6 (5) |
C6—C7—C8—C9 | −22.8 (6) | C15—C16—C17—C20 | 151.7 (4) |
C7—C8—C9—C11 | −179.3 (4) | C15—C16—C17—C13 | 20.5 (5) |
C14—C8—C9—C11 | −52.9 (4) | C18—C13—C17—C20 | −47.0 (5) |
C7—C8—C9—C10 | 51.4 (4) | C14—C13—C17—C20 | −165.7 (3) |
C14—C8—C9—C10 | 177.8 (3) | C12—C13—C17—C20 | 79.8 (4) |
C4—C5—C10—C1 | −25.0 (5) | C18—C13—C17—C16 | 78.9 (4) |
C6—C5—C10—C1 | 156.6 (4) | C14—C13—C17—C16 | −39.8 (4) |
C4—C5—C10—C19 | 91.7 (4) | C12—C13—C17—C16 | −154.3 (3) |
C6—C5—C10—C19 | −86.7 (4) | C16—C17—C20—C21 | −174.5 (4) |
C4—C5—C10—C9 | −146.1 (4) | C13—C17—C20—C21 | −53.1 (5) |
C6—C5—C10—C9 | 35.4 (4) | C16—C17—C20—C22 | 60.3 (4) |
O2—C1—C10—C5 | −47.5 (5) | C13—C17—C20—C22 | −178.3 (3) |
C2—C1—C10—C5 | 23.3 (5) | C21—C20—C22—C23 | 77.8 (5) |
O2—C1—C10—C19 | −164.6 (4) | C17—C20—C22—C23 | −155.3 (4) |
C2—C1—C10—C19 | −93.8 (4) | C20—C22—C23—C24 | −175.9 (4) |
O2—C1—C10—C9 | 72.7 (4) | C28—O3—C24—C25 | −103.7 (4) |
C2—C1—C10—C9 | 143.5 (4) | C28—O3—C24—C23 | 132.7 (3) |
C11—C9—C10—C5 | 175.0 (3) | C22—C23—C24—O3 | −61.7 (4) |
C8—C9—C10—C5 | −57.4 (4) | C22—C23—C24—C25 | 177.9 (4) |
C11—C9—C10—C1 | 54.1 (4) | O3—C24—C25—C27 | −60.1 (4) |
C8—C9—C10—C1 | −178.3 (3) | C23—C24—C25—C27 | 59.4 (5) |
C11—C9—C10—C19 | −65.7 (4) | O3—C24—C25—C26 | 65.2 (5) |
C8—C9—C10—C19 | 61.9 (4) | C23—C24—C25—C26 | −175.3 (4) |
C8—C9—C11—C12 | 51.4 (5) | C24—O3—C28—O4 | −3.0 (6) |
C10—C9—C11—C12 | 178.6 (4) | C24—O3—C28—C29 | 175.4 (3) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1W—H1W···O4 | 0.95 (6) | 2.15 (6) | 3.085 (18) | 174 (5) |
O1W—H2W···O1i | 1.03 (6) | 1.78 (6) | 2.799 (18) | 170 (5) |
C1—H1···O1ii | 0.98 | 2.46 | 3.430 (6) | 169 |
Symmetry codes: (i) −x, y−3/2, −z+1; (ii) −x, y−1/2, −z. |
Experimental details
Crystal data |
Chemical formula | C29H42O4·H2O |
Mr | 472.64 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 293 |
a, b, c (Å) | 10.642 (3), 11.719 (2), 10.977 (3) |
β (°) | 108.04 (2) |
V (Å3) | 1301.7 (6) |
Z | 2 |
Radiation type | Cu Kα |
µ (mm−1) | 0.64 |
Crystal size (mm) | 0.20 × 0.15 × 0.10 |
|
Data collection |
Diffractometer | Enraf-Nonius CAD-4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2848, 2712, 2262 |
Rint | 0.016 |
(sin θ/λ)max (Å−1) | 0.626 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.056, 0.162, 1.12 |
No. of reflections | 2712 |
No. of parameters | 322 |
No. of restraints | 1 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.27, −0.55 |
Selected geometric parameters (Å, º) topO1—C3 | 1.223 (5) | O3—C24 | 1.462 (4) |
O2—C1 | 1.431 (5) | O4—C28 | 1.194 (5) |
O2—C2 | 1.451 (5) | O1W—H1W | 0.94 (5) |
O3—C28 | 1.339 (4) | O1W—H2W | 1.03 (5) |
| | | |
C1—O2—C2 | 60.7 (3) | O2—C1—C10 | 117.9 (3) |
C28—O3—C24 | 119.0 (3) | O2—C2—C1 | 59.0 (3) |
O2—C1—C2 | 60.3 (3) | H1W—O1W—H2W | 111 (6) |
| | | |
C2—O2—C1—C10 | 112.9 (4) | C20—C22—C23—C24 | −175.9 (4) |
C1—O2—C2—C3 | −110.8 (4) | C22—C23—C24—C25 | 177.9 (4) |
O2—C1—C2—C3 | 101.3 (4) | C23—C24—C25—C26 | −175.3 (4) |
C13—C17—C20—C22 | −178.3 (3) | C24—O3—C28—C29 | 175.4 (3) |
C17—C20—C22—C23 | −155.3 (4) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1W—H1W···O4 | 0.95 (6) | 2.15 (6) | 3.085 (18) | 174 (5) |
O1W—H2W···O1i | 1.03 (6) | 1.78 (6) | 2.799 (18) | 170 (5) |
C1—H1···O1ii | 0.98 | 2.46 | 3.430 (6) | 169 |
Symmetry codes: (i) −x, y−3/2, −z+1; (ii) −x, y−1/2, −z. |
1α,24(R)-Dihydroxy vitamin D3 [tacalcitol, (I); Takeshita et al., 1977; Ochi et al.,1979; Okamoto et al., 1995; Fall et al., 1997] displays antipsoriatic activity. The title compound, (II), which contains 1a,2a-epoxide ring and a 24-acetate group is the major intermediate in the synthesis of vitamin D3 [tacalcitol, (I)]. The absolute configuration at C-24 in these molecules was assigned by physical methods involving optical rotation (Klyne & Stokes,1954) and NMR spectra (Ikekawa et al.,1975; Koizumi et al., 1975; Seki et al., 1975; Koch et al., 1983; Meenakshi et al., 1997).
We have synthesized intermediates (III) [24(R)-hydroxycholesta-1,4-dien-3-one] and (IV) [24(S)-hydroxycholesta-1,4-dien-3-one], which are epimeric at C-24, from the corresponding ketones (V) [24(R)-hydroxycholestan-3-one] and (VI) [24(S)-hydroxycholestan-3-one]. The title compound, (II), was synthesized from (III) involving aceylation, bromination, dehydrobromination and epoxidation. The melting point (393–395 K; Ochi et al., 1979) of epimer (III) agrees with the reported values, while the melting point of the title compound is 373–375 K. There is a solvent water molecule present in the structure. The packing of the molecule is established by inter and intramolecular C—H···O and O—H···O hydrogen bonds. Water H atoms were fixed using the program HYDROGEN (Nardelli, 1999).
Rings A (C1–C10), B (C5–C10), C (C8–C14) and D (C13–C17) adopt sofa, sofa, chair and envelope conformations, respectively. Substituents at C8 and C9, and C13 and C14 are at diaxial positions in the cyclohexane rings leading to a trans conformation [torsion angles H8—C8—C9—H9 = 179° and C18—C13—C14—H14 = 177°]. The priority sequence attached to the chiral carbon C24 has an `R' designation as per the listed coordinates. The absolute conformation could not be determined unequivocally as the structure contains only light atoms. The side chain attached to the D ring is in an all-trans conformation.
The best plane passing through ring A makes a dihedral angle of 14.2 (1)° with the best plane passing through cyclohexane ring B. The dihedral angles between rings B and C, and between rings C and D are 8.7 (2) and 9.6 (2)°, respectively.