supplementary materials


im2347 scheme

Acta Cryst. (2012). E68, o237    [ doi:10.1107/S1600536811054249 ]

5[alpha],6[alpha]-Epoxy-7-norcholestan-3[beta]-yl acetate

L. C. R. Andrade, J. A. Paixão, M. J. M. de Almeida, J. F. S. Carvalho and M. M. Cruz Silva

Abstract top

The title cholestan, C28H46O3, was prepared by epoxidation of 7-norcholest-5-en-3[beta]-yl acetate and crystallized by slow evaporation from an ethanolic solution. All rings are trans fused. The 3[beta]-acetate and the 17[beta]-cholestane side chain are in equatorial positions. The molecule is highly twisted due to its B-nor characteristic. A quantum chemical ab-initio Roothaan Hartree-Fock calculation of the equilibrium geometry of the isolated molecule gives values for bond lengths and valency angles in close agreement with the experimental ones.

Comment top

Within our interest on the chemistry (Carvalho et al., 2009a, Carvalho et al., 2010a) and biological activity (Carvalho et al., 2009b, Carvalho et al., 2010b) of steroids, we have been exploring the cytotoxic potential of oxysterols and their synthetic analogues against a panel of cancer and normal cell lines. We found that several chemical features are important for cytotoxicity such as the cholestane side-chain, a free or an in vivo easily generated 3β-hydroxyl group and the presence of an additional hydroxyl group at either 6β- or 7β-position. B-Norsteroids comprise a particular class of steroids, which bear a five-membered ring B, instead of the usual six-membered ring. As discussed recently (Uyanik & Hanson, 2009) this structural characteristic affects the outcome of many reactions, and quite often unexpected products are obtained. On the other hand, very few studies address the consequences of a shorter ring B in biological outcome comparatively to the normal six-membered analogs. We have recently found that an α-epoxide in position C5 and C6 of a cholestane affords different cytotoxic results, when ring B bears only five carbons, instead of the usual six-membered ring B of cholesterol. Specifically, the B-nor-α-epoxycholestane displays a higher cytotoxicity (IC50 = 40.9 µM) than the six-membered ring B analogue (IC50 > 65 µM) (Carvalho et al., 2009b). We hypothesized that such biological result must be correlated with the α-orientation of the two epoxycholestane derivates. In this way, the evaluation of the three-dimensional structure of compound (I) by X-ray crystallography will contribute to correlate the importance of the geometry of ring B and the orientation of the epoxy moiety with the biological effect observed. Single crystal diffraction measurements allowed us to conclude that ring bond lengths have normal values (Allen et al.,1987) with average C(sp3)–C(sp3) of 1.530 (3) Å, excluding the shorter C5–C6 bond of 1.458 (3) Å. The cholestane side-chain shows C(sp3)–C(sp3) bond lengths varying from C24–C25 [1.480 (4) Å] up to C17–C20 [1.540 (3) Å]. Rings A and C have slightly flattened chair conformations. The five membered ring B assumes a 9α-envelope conformation [pseudo-rotation (Altona et al., 1968; Duax & Norton, 1975): ΔCs(9)=3.0 (3), ΔCs(7)=24.8 (3); ΔC2(7,9)=15.0 (3); Δ=173.0 (8); φ=37.9 (2)°; puckering parameters (Cremer & Pople, 1975) q2=0.374 (3) Å and φ2=285.2 (5)°]. Ring D has a 13β,14α-half chair conformation [ΔC2(13,14)=3.4 (3), ΔCs(14)=20.0 (3); ΔCs(13)=15.8 (3); Δ=5.0 (6); φ=47.2 (2)°; q2=0.465 (3) Å and φ2=194.9 (4)°]. A pseudo-torsion C19–C10···C13–C18 angle of 12.68 (18)° indicates that, due to the B-nor characteristic, the molecule is highly twisted. Both the 3β-acetate and the 17β-cholestane side-chain are in equatorial positions with angles 66.5 (2) and 65.6 (2)°, respectively. The 5α,6α epoxy plane makes an angle of 83.93 (14)° with the five membered B ring.

In order to gain some insight on how the crystal packing of (I) might affect the molecular geometry we have performed Hartree-Fock quantum chemical calculation using the GAMESS code (Schmidt et al., 1993), of the equilibrium geometry for the free molecule.

These ab-initio calculations reproduce well the observed bond lengths and valency angles of the molecule with the exception of a few C–C bonds in the cholestane ligand that are somewhat larger than the measured values, probably as a result of the larger displacement ellipsoids of these atoms. The calculation also reproduces the observed molecular conformation, with puckering parameters that agree well with those determined from the crystallographic study. The high value of the pseudo-torsion angle is well reproduced by the calculations (obs: 12.68 (18), calc: 13.5°). The calculated configuration of the 3β-acetate and the 17β-cholestane side-chain are also close to those observed in the crystal.

Since there is no strong hydrogen bond donor in the molecule, cohesion of the crystal structure can only be attributed to van der Waals interactions.

Related literature top

For the chemistry of the title compound, see: Carvalho et al. (2009a, 2010a). For studies of biological activity of steroids, see: Carvalho et al. (2009b, 2010b). For the influence of structural characteristics of B-nor steroids on the outcome of many reactions, see: Uyanik & Hanson (2009). For asymmetry parameters, see: Duax & Norton (1975); Altona et al. (1968). For reference bond-length data, see: Allen et al. (1987). For puckering parameters, see: Cremer & Pople (1975). For the melting point of the title compound, see: Joska et al. (1963). For the software used in ab-initio calculations, see Schmidt et al. (1993).

Experimental top

Synthesis of (I) was performed as described in the literature (Carvalho et al., 2009a). Epoxidation of 7-norcholest-5-en-3β-yl acetate in acetonitrile at reflux temperature affords the α-epoxide in high yield (around 90%) in 10 minutes. Crystallization was performed at room temperature by slow evaporation from an ethanolic solution. Mp 386–386.5 K (EtOH); lit., (Joska et al., 1963) 384–385 K.

Refinement top

All hydrogen atoms were refined as riding on their parent atoms using SHELXL97 defaults. Number of Friedel pairs measured: 2848 (85%). Due to the lack of any strong anomalous scatterer atom at the Mo Kα wavelength, refinement of Flack's parameter was inconclusive. However, the absolute configuration of the molecule is known from the synthetic route.

Computing details top

Data collection: SMART (Bruker, 2003); cell refinement: SAINT (Bruker, 2003); data reduction: SAINT (Bruker, 2003); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. ORTEPII plot of the title compound. Displacement ellipsoids are drawn at the 50% level.
5α,6α-Epoxy-7-norcholestan-3β-yl acetate top
Crystal data top
C28H46O3Dx = 1.075 Mg m3
Mr = 430.65Melting point: 386 K
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
a = 7.5820 (1) ÅCell parameters from 9561 reflections
b = 9.7487 (1) Åθ = 2.4–21.0°
c = 17.8588 (2) ŵ = 0.07 mm1
β = 93.1792 (18)°T = 293 K
V = 1318.00 (3) Å3Prism, colourless
Z = 20.44 × 0.24 × 0.16 mm
F(000) = 476
Data collection top
Bruker APEX CCD area-detector
diffractometer
6194 independent reflections
Radiation source: fine-focus sealed tube3551 reflections with I > 2σ(I)
graphiteRint = 0.030
φ and ω scansθmax = 28.0°, θmin = 2.3°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2000)
h = 99
Tmin = 0.981, Tmax = 0.989k = 1212
35109 measured reflectionsl = 2223
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.048H-atom parameters constrained
wR(F2) = 0.138 w = 1/[σ2(Fo2) + (0.0668P)2 + 0.1597P]
where P = (Fo2 + 2Fc2)/3
S = 0.96(Δ/σ)max < 0.001
6194 reflectionsΔρmax = 0.23 e Å3
286 parametersΔρmin = 0.14 e Å3
1 restraintAbsolute structure: Flack (1983), 2846 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.5 (15)
Crystal data top
C28H46O3V = 1318.00 (3) Å3
Mr = 430.65Z = 2
Monoclinic, P21Mo Kα radiation
a = 7.5820 (1) ŵ = 0.07 mm1
b = 9.7487 (1) ÅT = 293 K
c = 17.8588 (2) Å0.44 × 0.24 × 0.16 mm
β = 93.1792 (18)°
Data collection top
Bruker APEX CCD area-detector
diffractometer
6194 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2000)
3551 reflections with I > 2σ(I)
Tmin = 0.981, Tmax = 0.989Rint = 0.030
35109 measured reflectionsθmax = 28.0°
Refinement top
R[F2 > 2σ(F2)] = 0.048H-atom parameters constrained
wR(F2) = 0.138Δρmax = 0.23 e Å3
S = 0.96Δρmin = 0.14 e Å3
6194 reflectionsAbsolute structure: Flack (1983), 2846 Friedel pairs
286 parametersFlack parameter: 0.5 (15)
1 restraint
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
xyzUiso*/Ueq
C90.9354 (3)0.4824 (2)0.25045 (11)0.0496 (5)
H90.88030.40120.27150.060*
O560.59348 (19)0.50504 (19)0.26154 (8)0.0663 (4)
C100.8357 (3)0.5092 (2)0.17350 (11)0.0537 (5)
O30.3659 (2)0.5251 (2)0.03122 (9)0.0795 (5)
C121.1969 (3)0.4357 (2)0.33813 (13)0.0561 (5)
H12A1.14750.35120.35660.067*
H12B1.32440.42650.34090.067*
C131.1450 (3)0.5549 (2)0.38854 (11)0.0492 (5)
C70.8837 (3)0.6045 (2)0.29938 (12)0.0517 (5)
H70.95160.68410.28380.062*
C140.9426 (3)0.5733 (2)0.37979 (11)0.0521 (5)
H140.88940.48540.39260.062*
C201.3527 (3)0.5455 (3)0.51411 (12)0.0631 (6)
H201.39280.63980.50680.076*
C171.1673 (3)0.5317 (2)0.47510 (11)0.0563 (5)
H171.12570.43860.48500.068*
C111.1318 (3)0.4564 (3)0.25588 (12)0.0597 (6)
H11A1.19290.53370.23500.072*
H11B1.15830.37540.22710.072*
C60.6944 (3)0.6292 (3)0.27422 (13)0.0621 (6)
H60.63530.71380.28860.075*
C50.6662 (3)0.5752 (2)0.19835 (13)0.0573 (6)
C30.4844 (3)0.4820 (3)0.09382 (13)0.0672 (7)
H30.42290.41830.12590.081*
C10.7853 (3)0.3819 (3)0.12798 (13)0.0670 (6)
H1A0.73920.31310.16100.080*
H1B0.89010.34440.10680.080*
C181.2455 (3)0.6852 (3)0.36837 (14)0.0664 (6)
H18A1.37030.66930.37550.100*
H18B1.21220.75920.40010.100*
H18C1.21690.70870.31690.100*
C190.9377 (3)0.6129 (3)0.12773 (14)0.0754 (7)
H19A0.86800.63730.08320.113*
H19B1.04690.57270.11410.113*
H19C0.96200.69360.15730.113*
C211.4874 (4)0.4498 (3)0.48156 (17)0.0861 (8)
H21A1.59500.45200.51250.129*
H21B1.51060.47910.43170.129*
H21C1.44160.35800.47990.129*
C221.3466 (4)0.5206 (3)0.59896 (13)0.0799 (8)
H22A1.24170.56440.61650.096*
H22B1.33560.42290.60760.096*
C161.0325 (4)0.6318 (3)0.50653 (15)0.0787 (8)
H16A1.09260.71200.52760.094*
H16B0.96960.58770.54580.094*
C40.5304 (3)0.6124 (3)0.13705 (14)0.0668 (7)
H4A0.57760.68050.10400.080*
H4B0.42580.65000.15840.080*
O280.2305 (3)0.3225 (3)0.02880 (15)0.1146 (8)
C280.2462 (4)0.4337 (4)0.00463 (16)0.0817 (8)
C20.6466 (4)0.4123 (3)0.06445 (14)0.0770 (8)
H2A0.69790.47120.02770.092*
H2B0.61140.32720.03970.092*
C150.9018 (3)0.6743 (3)0.44114 (13)0.0730 (7)
H15A0.78040.66560.45500.088*
H15B0.92250.76800.42560.088*
C241.5074 (5)0.5303 (4)0.72649 (15)0.1002 (10)
H24A1.39640.55770.74650.120*
H24B1.51320.43090.72880.120*
C231.5041 (4)0.5726 (4)0.64467 (15)0.0975 (10)
H23A1.50580.67200.64180.117*
H23B1.61030.53890.62300.117*
C290.1328 (4)0.4931 (4)0.05840 (16)0.1031 (11)
H29A0.20180.50490.10140.155*
H29B0.08790.58040.04350.155*
H29C0.03610.43220.07080.155*
C251.6529 (5)0.5861 (4)0.77614 (16)0.0989 (10)
H251.64270.68630.77430.119*
C261.8343 (5)0.5507 (5)0.7531 (2)0.1229 (13)
H26A1.85340.45390.75880.184*
H26B1.92040.59960.78420.184*
H26C1.84520.57610.70160.184*
C271.6293 (6)0.5434 (6)0.85708 (18)0.1511 (18)
H27A1.51490.57190.87170.227*
H27B1.71900.58590.88930.227*
H27C1.63910.44550.86130.227*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C90.0499 (11)0.0536 (12)0.0447 (11)0.0052 (9)0.0024 (9)0.0030 (9)
O560.0528 (9)0.0922 (12)0.0533 (9)0.0007 (9)0.0012 (7)0.0018 (9)
C100.0518 (12)0.0643 (14)0.0442 (11)0.0041 (11)0.0034 (9)0.0013 (10)
O30.0679 (10)0.1045 (14)0.0629 (10)0.0054 (11)0.0248 (8)0.0075 (11)
C120.0522 (12)0.0576 (13)0.0574 (13)0.0101 (10)0.0069 (10)0.0014 (11)
C130.0520 (12)0.0456 (11)0.0492 (11)0.0046 (9)0.0056 (9)0.0013 (9)
C70.0507 (12)0.0520 (12)0.0515 (12)0.0073 (10)0.0058 (10)0.0058 (10)
C140.0537 (12)0.0537 (12)0.0480 (11)0.0056 (10)0.0037 (9)0.0049 (10)
C200.0712 (15)0.0587 (14)0.0569 (13)0.0026 (12)0.0204 (11)0.0066 (11)
C170.0622 (13)0.0559 (13)0.0495 (12)0.0048 (11)0.0094 (10)0.0047 (11)
C110.0570 (13)0.0693 (15)0.0520 (12)0.0161 (11)0.0043 (10)0.0080 (11)
C60.0560 (14)0.0711 (15)0.0580 (14)0.0173 (12)0.0088 (11)0.0121 (12)
C50.0512 (12)0.0651 (14)0.0545 (13)0.0078 (10)0.0074 (10)0.0004 (11)
C30.0590 (14)0.0877 (17)0.0529 (13)0.0013 (13)0.0150 (11)0.0025 (13)
C10.0660 (15)0.0805 (16)0.0531 (14)0.0097 (13)0.0100 (11)0.0131 (12)
C180.0660 (15)0.0608 (14)0.0704 (16)0.0063 (12)0.0149 (12)0.0130 (12)
C190.0682 (16)0.103 (2)0.0546 (14)0.0009 (14)0.0025 (12)0.0167 (14)
C210.0722 (17)0.099 (2)0.0840 (19)0.0175 (15)0.0279 (14)0.0004 (16)
C220.0922 (18)0.0841 (19)0.0598 (14)0.0182 (16)0.0270 (13)0.0073 (14)
C160.0785 (18)0.098 (2)0.0579 (15)0.0101 (15)0.0103 (13)0.0162 (14)
C40.0556 (14)0.0803 (17)0.0626 (14)0.0086 (12)0.0129 (11)0.0033 (13)
O280.127 (2)0.0950 (16)0.1150 (19)0.0149 (15)0.0555 (15)0.0021 (14)
C280.0705 (17)0.107 (2)0.0651 (17)0.0073 (17)0.0157 (14)0.0145 (17)
C20.0760 (17)0.096 (2)0.0565 (15)0.0054 (14)0.0159 (13)0.0154 (14)
C150.0675 (15)0.0909 (18)0.0591 (15)0.0183 (14)0.0095 (12)0.0236 (14)
C240.121 (2)0.113 (2)0.0625 (16)0.030 (2)0.0267 (16)0.0080 (18)
C230.108 (2)0.112 (2)0.0685 (17)0.0300 (19)0.0324 (15)0.0102 (17)
C290.094 (2)0.128 (3)0.083 (2)0.008 (2)0.0386 (16)0.007 (2)
C250.115 (3)0.106 (2)0.0716 (19)0.010 (2)0.0314 (18)0.0022 (17)
C260.103 (3)0.152 (3)0.110 (3)0.003 (3)0.026 (2)0.006 (3)
C270.167 (4)0.214 (5)0.068 (2)0.035 (4)0.033 (2)0.011 (3)
Geometric parameters (Å, °) top
C9—C111.509 (3)C18—H18B0.9600
C9—C71.540 (3)C18—H18C0.9600
C9—C101.553 (3)C19—H19A0.9600
C9—H90.9800C19—H19B0.9600
O56—C61.443 (3)C19—H19C0.9600
O56—C51.454 (3)C21—H21A0.9600
C10—C11.521 (3)C21—H21B0.9600
C10—C51.525 (3)C21—H21C0.9600
C10—C191.535 (3)C22—C231.497 (4)
O3—C281.340 (4)C22—H22A0.9700
O3—C31.457 (3)C22—H22B0.9700
C12—C131.534 (3)C16—C151.546 (4)
C12—C111.537 (3)C16—H16A0.9700
C12—H12A0.9700C16—H16B0.9700
C12—H12B0.9700C4—H4A0.9700
C13—C181.535 (3)C4—H4B0.9700
C13—C141.544 (3)O28—C281.175 (4)
C13—C171.562 (3)C28—C291.495 (4)
C7—C61.500 (3)C2—H2A0.9700
C7—C141.511 (3)C2—H2B0.9700
C7—H70.9800C15—H15A0.9700
C14—C151.518 (3)C15—H15B0.9700
C14—H140.9800C24—C251.480 (4)
C20—C211.522 (4)C24—C231.517 (4)
C20—C221.538 (3)C24—H24A0.9700
C20—C171.540 (3)C24—H24B0.9700
C20—H200.9800C23—H23A0.9700
C17—C161.542 (4)C23—H23B0.9700
C17—H170.9800C29—H29A0.9600
C11—H11A0.9700C29—H29B0.9600
C11—H11B0.9700C29—H29C0.9600
C6—C51.458 (3)C25—C261.497 (5)
C6—H60.9800C25—C271.524 (4)
C5—C41.505 (3)C25—H250.9800
C3—C41.517 (4)C26—H26A0.9600
C3—C21.524 (4)C26—H26B0.9600
C3—H30.9800C26—H26C0.9600
C1—C21.533 (3)C27—H27A0.9600
C1—H1A0.9700C27—H27B0.9600
C1—H1B0.9700C27—H27C0.9600
C18—H18A0.9600
C11—C9—C7112.00 (17)H18A—C18—H18C109.5
C11—C9—C10121.01 (17)H18B—C18—H18C109.5
C7—C9—C10104.22 (16)C10—C19—H19A109.5
C11—C9—H9106.2C10—C19—H19B109.5
C7—C9—H9106.2H19A—C19—H19B109.5
C10—C9—H9106.2C10—C19—H19C109.5
C6—O56—C560.45 (15)H19A—C19—H19C109.5
C1—C10—C5107.96 (18)H19B—C19—H19C109.5
C1—C10—C19111.84 (19)C20—C21—H21A109.5
C5—C10—C19109.6 (2)C20—C21—H21B109.5
C1—C10—C9115.54 (19)H21A—C21—H21B109.5
C5—C10—C9100.95 (16)C20—C21—H21C109.5
C19—C10—C9110.31 (18)H21A—C21—H21C109.5
C28—O3—C3117.2 (2)H21B—C21—H21C109.5
C13—C12—C11112.47 (17)C23—C22—C20114.7 (2)
C13—C12—H12A109.1C23—C22—H22A108.6
C11—C12—H12A109.1C20—C22—H22A108.6
C13—C12—H12B109.1C23—C22—H22B108.6
C11—C12—H12B109.1C20—C22—H22B108.6
H12A—C12—H12B107.8H22A—C22—H22B107.6
C12—C13—C18110.04 (18)C17—C16—C15107.76 (19)
C12—C13—C14108.29 (17)C17—C16—H16A110.2
C18—C13—C14112.56 (17)C15—C16—H16A110.2
C12—C13—C17116.99 (17)C17—C16—H16B110.2
C18—C13—C17108.93 (18)C15—C16—H16B110.2
C14—C13—C1799.73 (15)H16A—C16—H16B108.5
C6—C7—C14123.00 (19)C5—C4—C3107.3 (2)
C6—C7—C9102.89 (17)C5—C4—H4A110.3
C14—C7—C9108.20 (16)C3—C4—H4A110.3
C6—C7—H7107.3C5—C4—H4B110.3
C14—C7—H7107.3C3—C4—H4B110.3
C9—C7—H7107.3H4A—C4—H4B108.5
C7—C14—C15119.57 (18)O28—C28—O3124.3 (3)
C7—C14—C13111.05 (16)O28—C28—C29124.7 (3)
C15—C14—C13104.11 (17)O3—C28—C29111.0 (3)
C7—C14—H14107.2C3—C2—C1111.4 (2)
C15—C14—H14107.2C3—C2—H2A109.3
C13—C14—H14107.2C1—C2—H2A109.3
C21—C20—C22109.7 (2)C3—C2—H2B109.3
C21—C20—C17112.9 (2)C1—C2—H2B109.3
C22—C20—C17110.8 (2)H2A—C2—H2B108.0
C21—C20—H20107.7C14—C15—C16102.9 (2)
C22—C20—H20107.7C14—C15—H15A111.2
C17—C20—H20107.7C16—C15—H15A111.2
C20—C17—C16112.78 (19)C14—C15—H15B111.2
C20—C17—C13118.75 (18)C16—C15—H15B111.2
C16—C17—C13103.37 (17)H15A—C15—H15B109.1
C20—C17—H17107.1C25—C24—C23116.7 (3)
C16—C17—H17107.1C25—C24—H24A108.1
C13—C17—H17107.1C23—C24—H24A108.1
C9—C11—C12110.30 (18)C25—C24—H24B108.1
C9—C11—H11A109.6C23—C24—H24B108.1
C12—C11—H11A109.6H24A—C24—H24B107.3
C9—C11—H11B109.6C22—C23—C24113.8 (3)
C12—C11—H11B109.6C22—C23—H23A108.8
H11A—C11—H11B108.1C24—C23—H23A108.8
O56—C6—C560.15 (14)C22—C23—H23B108.8
O56—C6—C7113.77 (18)C24—C23—H23B108.8
C5—C6—C7108.02 (18)H23A—C23—H23B107.7
O56—C6—H6120.1C28—C29—H29A109.5
C5—C6—H6120.1C28—C29—H29B109.5
C7—C6—H6120.1H29A—C29—H29B109.5
O56—C5—C659.41 (15)C28—C29—H29C109.5
O56—C5—C4113.85 (19)H29A—C29—H29C109.5
C6—C5—C4130.4 (2)H29B—C29—H29C109.5
O56—C5—C10112.92 (18)C24—C25—C26114.6 (3)
C6—C5—C10109.87 (17)C24—C25—C27110.2 (3)
C4—C5—C10116.33 (19)C26—C25—C27110.8 (3)
O3—C3—C4105.3 (2)C24—C25—H25106.9
O3—C3—C2109.85 (19)C26—C25—H25106.9
C4—C3—C2112.4 (2)C27—C25—H25106.9
O3—C3—H3109.7C25—C26—H26A109.5
C4—C3—H3109.7C25—C26—H26B109.5
C2—C3—H3109.7H26A—C26—H26B109.5
C10—C1—C2112.3 (2)C25—C26—H26C109.5
C10—C1—H1A109.1H26A—C26—H26C109.5
C2—C1—H1A109.1H26B—C26—H26C109.5
C10—C1—H1B109.1C25—C27—H27A109.5
C2—C1—H1B109.1C25—C27—H27B109.5
H1A—C1—H1B107.9H27A—C27—H27B109.5
C13—C18—H18A109.5C25—C27—H27C109.5
C13—C18—H18B109.5H27A—C27—H27C109.5
H18A—C18—H18B109.5H27B—C27—H27C109.5
C13—C18—H18C109.5
C11—C9—C10—C182.1 (3)C6—O56—C5—C10100.3 (2)
C7—C9—C10—C1150.83 (18)C7—C6—C5—O56107.6 (2)
C11—C9—C10—C5161.8 (2)O56—C6—C5—C496.5 (3)
C7—C9—C10—C534.7 (2)C7—C6—C5—C4155.9 (2)
C11—C9—C10—C1946.0 (3)O56—C6—C5—C10105.5 (2)
C7—C9—C10—C1981.1 (2)C7—C6—C5—C102.1 (3)
C11—C12—C13—C1867.9 (2)C1—C10—C5—O5677.9 (2)
C11—C12—C13—C1455.6 (2)C19—C10—C5—O56160.12 (18)
C11—C12—C13—C17167.16 (19)C9—C10—C5—O5643.8 (2)
C11—C9—C7—C6169.22 (19)C1—C10—C5—C6142.1 (2)
C10—C9—C7—C636.7 (2)C19—C10—C5—C695.9 (2)
C11—C9—C7—C1459.2 (2)C9—C10—C5—C620.5 (2)
C10—C9—C7—C14168.28 (17)C1—C10—C5—C456.5 (3)
C6—C7—C14—C1558.0 (3)C19—C10—C5—C465.5 (3)
C9—C7—C14—C15177.5 (2)C9—C10—C5—C4178.1 (2)
C6—C7—C14—C13179.2 (2)C28—O3—C3—C4150.8 (2)
C9—C7—C14—C1361.2 (2)C28—O3—C3—C287.9 (3)
C12—C13—C14—C759.8 (2)C5—C10—C1—C252.3 (3)
C18—C13—C14—C762.1 (2)C19—C10—C1—C268.3 (3)
C17—C13—C14—C7177.40 (17)C9—C10—C1—C2164.4 (2)
C12—C13—C14—C15170.26 (19)C21—C20—C22—C2372.5 (3)
C18—C13—C14—C1567.9 (2)C17—C20—C22—C23162.2 (3)
C17—C13—C14—C1547.5 (2)C20—C17—C16—C15146.4 (2)
C21—C20—C17—C16178.2 (2)C13—C17—C16—C1516.9 (3)
C22—C20—C17—C1658.2 (3)O56—C5—C4—C376.4 (3)
C21—C20—C17—C1357.1 (3)C6—C5—C4—C3145.6 (3)
C22—C20—C17—C13179.3 (2)C10—C5—C4—C357.5 (3)
C12—C13—C17—C2079.4 (3)O3—C3—C4—C5174.84 (19)
C18—C13—C17—C2046.1 (2)C2—C3—C4—C555.2 (3)
C14—C13—C17—C20164.20 (19)C3—O3—C28—O280.5 (4)
C12—C13—C17—C16154.9 (2)C3—O3—C28—C29179.1 (2)
C18—C13—C17—C1679.6 (2)O3—C3—C2—C1172.8 (2)
C14—C13—C17—C1638.4 (2)C4—C3—C2—C155.9 (3)
C7—C9—C11—C1255.5 (2)C10—C1—C2—C354.3 (3)
C10—C9—C11—C12179.0 (2)C7—C14—C15—C16161.8 (2)
C13—C12—C11—C954.3 (3)C13—C14—C15—C1637.1 (3)
C5—O56—C6—C797.9 (2)C17—C16—C15—C1412.1 (3)
C14—C7—C6—O5681.5 (3)C20—C22—C23—C24172.1 (3)
C9—C7—C6—O5640.5 (2)C25—C24—C23—C22175.9 (3)
C14—C7—C6—C5146.1 (2)C23—C24—C25—C2658.7 (5)
C9—C7—C6—C524.1 (2)C23—C24—C25—C27175.5 (4)
C6—O56—C5—C4124.2 (2)C19—C10—C13—C1812.68 (18)
Acknowledgements top

This work was supported by funds from FEDER via the COMPETE (Programa Operacional Factores de Competitividade) programme and by the FCT (Fundação para a Ciência e a Tecnologia) (project PEst-C/FIS/UI0036/2011). We gratefully acknowledge the LCA–UC for a grant of computer time in the Milipeia cluster.

references
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