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Acta Cryst. (2011). E67, o1056-o1057    [ doi:10.1107/S1600536811011706 ]

3[beta],5[alpha],6[beta]-Trihydroxyandrostan-17-one

L. C. R. Andrade, M. J. B. M. de Almeida, J. A. Paixão, J. F. S. Carvalho and M. L. Sá e Melo

Abstract top

The title compound, C19H30O4, is an androstan-17-one derivative synthesized from the dehydroepiandrosterone through a sequential addition of an oxidant, followed by a trans-diaxial opening of the epoxide generated, with Bi(OTf)3 (OTf is trifluoromethanesulfonate). The six-membered rings have a slightly flattened chair conformation, while the five-membered ring adopts a 14-[alpha] envelope conformation. All rings are trans fused. In the crystal, the molecules are connected by O-H...O hydrogen bonds involving the hydroxyl and carbonyl groups, forming a three-dimensional network. A quantum mechanical ab initio Roothan Hartree-Fock calculation of the free molecule gives bond lengths, valency angles and ring torsion angles of the free molecule at equilibrium geometry (energy minimum) close to the experimental values.

Comment top

Recently, the importance of natural products as scaffolds for drug discovery and design has been a subject of renewed interest (Li & Vederas, 2009; Rosén et al., 2009). The 3β,5α,6β-hydroxylation pattern is found in several natural products (Mizushina et al., 1999; Hata et al., 2002; Tanaka et al., 2002; Sun et al., 2006) and also in human tissues, mainly in an oxidation product of cholesterol. The same hydroxylation motif is present in several natural steroids with interesting biological properties, namely cytotoxicity against cancer cells (Aiello et al., 1995; El-Gamal et al., 2004). On the other hand, cholestane-3β,5α,6β-triol has been extensively studied, proving to display cytotoxicity (Carvalho et al., 2010a) and angiotoxicity (Imai et al., 1980; Peng et al., 1985) and has been suggested to participate in the in vivo genesis of pathological situations such as osteoporosis (Hongmei et al., 2005) and atherosclerosis (Imai et al., 1980; Peng et al., 1985). Such findings validate the 3β,5α,6β-hydroxylation pattern as biologically important, and in this context a recently new protocol for the straightforward synthesis of 5α,6β-dihydroxy-steroids from a broad diversity of 3β-hydroxy-Δ5-steroids was accomplished by our group (Carvalho et al., 2010b).

In addition, 3β,5α,6β-trihydroxy steroids are valuable intermediates for the synthesis of Δ4-3,6-dione-steroids, widely present in natural products (Tischler et al., 1988; Aiello et al., 1991; Pardo et al., 2000) and with proved utility as molecular probes for the study of aromatase inhibition (Numazawa & Tachibana, 1994; Pérez-Ornelas et al., 2005; Nagaoka & Numazawa, 2004). In fact, compound (I) is a synthetically valuable intermediate (Ehrenstein, 1939) of the biologically active androst-4-ene-3,6,17-trione compound, (Anthony et al., 1999) which is a well known aromatase inhibitor (Numazawa et al., 1987). Due to the interest of our group in the cytotoxic potential of steroids, a series of oxygenated steroids were further prepared and evaluated on HT-29 cancer cells (Carvalho et al., 2010a). Compound (I) showed no relevant cytotoxicity (IC50 > 50µM), in contrast to cholestane-3β,5α,6β-triol and other cholestane derivatives. Such result points to the importance of a C-17 cholesteryl type side chain for cytotoxicity thus the importance of X-ray difraction structural studies on such compounds.

Bond lengths and valency angles are within the range of expected values for this type of compounds (Allen et al.,1987) with the exception of bonds C2–C3 and C3–C4 [1.510 (3); 1.518 (3) Å)] which are significantely smaller than the Csp3–Csp3 average value [1.535 Å].

Rings A to C have slightly flattened chair conformations, as shown by the Cremer & Pople (1975) parameters [ring A: Q = 0.570 (2) Å, θ = 5.6 (2)° and φ = 299 (2)°; B: Q = 0.5705 (19) Å, θ = 3.4 (2)° and φ = 255 (3)°; C: Q = 0.5727 (19) Å, θ = 7.04 (19)° and φ = 271.3 (16)°].

Ring D has a 14-α envelope conformation [Cremer & Pople (1975) parameters q2 = 0.415 (2) Å and φ2 = 213.5 (3)° and asymmetry parameters (Duax & Norton, 1975; Altona et al., 1968) ΔCs(14) =2.4 (2)°; ΔC2(13,14)=17.8 (2)°; φm=42.6 (1)°; Δ=30.6 (4)°]. All rings are fused trans.

In order to gain some insight on how the crystal packing of (I) might affect the molecular geometry we have performed quantum chemical calculations on the equilibrium geometry of the free molecule. The calculations were performed with the computer program GAMESS (Schmidt et al., 1993).

The ab-initio calculations reproduce well the observed experimental bond lengths and valency angles of the molecule. Also, the calculated conformation of the rings are very close to the experimental values.

The molecules are hydrogen-bonded via the hydroxyl and carbonyl groups forming a three-dimension hydrogen bond pattern. Each hydroxyl group acts as both donnor and acceptor, thus full potential for hydrogen bonding is achieved in the crystal struture. In addition to these bonds, three weak intramolecular interactions can be spotted involving atoms O5 and O6 and CH, CH2 and CH3 groups.

Related literature top

For the synthesis of the title compound, see: Carvalho et al. (2010b). For 3β,5α,6β-hydroxylation pattern occurance in several natural products, see: Mizushina et al. (1999); Hata et al. (2002); Tanaka et al. (2002); Sun et al. (2006). For natural products as scaffolds for drug discovery, see: Li & Vederas (2009); Rosén et al. (2009). For angiotoxicity of 3β,5α,6β-trihydroxy steroids, see: Imai et al. (1980); Peng et al. (1985). For the in vivo genesis of osteoporosis and atherosclerosis, see: Hongmei et al. (2005); Imai et al. (1980); Peng et al. (1985). For the cytotoxicity of steroids with a 3β,5α,6β-hydroxylation motif against cancer cells, see: Aiello et al. (1995); Carvalho et al. (2010a); El-Gamal et al. (2004). For the use of 3β,5α,6β-trihydroxy steroids in the synthesis of Δ4-3,6-dione steroids. see: Tischler et al. (1988); Aiello et al. (1991); Pardo et al. (2000). For their use as molecular probes for the study of aromatase inhibition, see: Numazawa & Tachibana (1994); Pérez-Ornelas et al. (2005); Nagaoka & Numazawa (2004). For the use of the title compound as an intermediate in the synthesis of the aromatase inhibitor androst-4-ene-3,6,17-trione, see: Ehrenstein (1939); Numazawa et al. (1987); Anthony et al. (1999). For related structures, see Anthony et al. (1999). For puckering parameters, see: Cremer & Pople (1975) and for asymmetry parameters, see: Duax & Norton (1975); Altona et al. (1968). For reference bond-length data, see: Allen et al. (1987). For the program GAMESS used to perform the quantum chemical calculations, see: Schmidt et al. (1993).

Experimental top

Synthesis of (I) was performed using a new and recently reported (Carvalho et al., 2010b) fast and high yielding sequential chemical approach for the straightforward preparation of 5α,6β-dihydroxy-steroids using 3β-hydroxy-Δ5-steroids as raw materials. The protocol involves two steps: (i) formation of the epoxide from Δ5-steroids, using MMPP as oxidative agent; and (ii) trans-diaxial epoxide opening with Bi(OTf)3 in commercial acetone. Crystallization from ethanol at room temperature afforded colorless crystals suitable for X-ray analysis. Analytical data of compound (I) is in accordance with the literature (Carvalho et al., 2010b).

Refinement top

All hydrogen atoms were refined as riding on their parent atoms using SHELXL97 defaults. The absolute configuration was not determined from the X-ray data, as the molecule lacks any strong anomalous scatterer atom at the Mo Kα wavelength, but was known from the synthetic route. Friedel pairs were merged before refinement.

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); 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.
3β,5α,6β-Trihydroxyandrostan-17-one top
Crystal data top
C19H30O4Dx = 1.290 Mg m−3
Mr = 322.43Melting point: 574 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 6253 reflections
a = 5.8132 (1) Åθ = 3.1–30.3°
b = 13.3880 (3) ŵ = 0.09 mm−1
c = 21.3298 (5) ÅT = 293 K
V = 1660.04 (6) Å3Prism, colourless
Z = 40.23 × 0.13 × 0.13 mm
F(000) = 704
Data collection top
Bruker APEXII CCD area-detector
diffractometer		2276 independent reflections
Radiation source: fine-focus sealed tube1874 reflections with I > 2σ(I)
graphiteRint = 0.031
φ and ω scansθmax = 27.9°, θmin = 1.8°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2000)		h = −7→6
Tmin = 0.937, Tmax = 1.00k = −17→17
40718 measured reflectionsl = −27→25
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.037Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.098H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.0563P)2 + 0.2093P]
where P = (Fo2 + 2Fc2)/3
2276 reflections(Δ/σ)max < 0.001
213 parametersΔρmax = 0.20 e Å−3
0 restraintsΔρmin = −0.20 e Å−3
Crystal data top
C19H30O4V = 1660.04 (6) Å3
Mr = 322.43Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 5.8132 (1) ŵ = 0.09 mm−1
b = 13.3880 (3) ÅT = 293 K
c = 21.3298 (5) Å0.23 × 0.13 × 0.13 mm
Data collection top
Bruker APEXII CCD area-detector
diffractometer		2276 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2000)		1874 reflections with I > 2σ(I)
Tmin = 0.937, Tmax = 1.00Rint = 0.031
40718 measured reflectionsθmax = 27.9°
Refinement top
R[F2 > 2σ(F2)] = 0.037H-atom parameters constrained
wR(F2) = 0.098Δρmax = 0.20 e Å−3
S = 1.04Δρmin = −0.20 e Å−3
2276 reflectionsAbsolute structure: ?
213 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

Experimental. IR (film) 3442, 3348, 2942, 2861, 1723, 1471, 1373, 1077, 1047, 1030, 1001, 960, 874 cm-1; 1H NMR (300 MHz, DMSO-d6) δ p.p.m. 0.77 (3H, s, 18-CH3), 1.04 (3H, s, 19-CH3), 2.36 (1H, dd, J=19.0, 8.2 Hz), 3.35 (1H, m, 6α-H), 3.74 (1H, s, OH), 3.78 (1H, m, 3α-H), 4.22 (1H, d, J=5.8 Hz, OH), 4.51 (1H, d, J=4.3 Hz, OH); 13C NMR (75 MHz, DMSO-d6) δ p.p.m. 13.4, 16.2, 20.0, 21.4 (CH2), 29.6, 31.0 (CH2), 31.5 (CH2), 32.0 (CH2), 33.3 (CH2), 35.3 (CH2), 37.9 (C-10), 40.8 (CH2), 44.8, 47.2 (C-13), 50.5, 65.6, 73.8, 74.3 (C-5), 220.0 (C-17); MS m/z (%): 321.3 (9) [M—H]+, 293.2 (20), 280.4 (23), 265.5 (100), 250.2 (13), 90.3 (54).

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
O30.4447 (4)0.39692 (11)−0.03066 (6)0.0551 (5)
H30.41760.4562−0.03710.083*
O50.8749 (2)0.26939 (10)0.10844 (6)0.0344 (3)
H50.87880.21980.08600.052*
O60.3172 (3)0.20863 (13)0.18197 (7)0.0490 (4)
H6A0.23720.21820.15090.074*
O171.1224 (3)0.38845 (11)0.44942 (6)0.0396 (4)
C10.7513 (4)0.47124 (14)0.11921 (8)0.0304 (4)
H1A0.75550.53450.14140.036*
H1B0.90850.45270.10930.036*
C20.6166 (4)0.48453 (14)0.05810 (8)0.0358 (5)
H2A0.46420.50980.06760.043*
H2B0.69400.53340.03200.043*
C30.5956 (4)0.38742 (14)0.02260 (8)0.0334 (5)
H3A0.74850.36830.00750.040*
C40.5032 (4)0.30359 (13)0.06337 (8)0.0298 (4)
H4A0.50940.24140.04000.036*
H4B0.34330.31700.07330.036*
C50.6392 (3)0.29152 (13)0.12470 (8)0.0245 (4)
C60.5535 (4)0.20277 (14)0.16369 (9)0.0326 (5)
H60.57430.14190.13880.039*
C70.6922 (4)0.19194 (13)0.22384 (8)0.0333 (5)
H7A0.84780.17180.21330.040*
H7B0.62470.13950.24920.040*
C80.7015 (3)0.28834 (13)0.26229 (8)0.0248 (4)
H80.54540.30490.27620.030*
C90.7942 (3)0.37543 (13)0.22212 (7)0.0226 (4)
H90.94690.35490.20760.027*
C100.6459 (3)0.39125 (12)0.16226 (7)0.0219 (4)
C110.8298 (4)0.47172 (13)0.26035 (8)0.0332 (5)
H11A0.90740.52050.23420.040*
H11B0.68050.49890.27140.040*
C120.9702 (4)0.45672 (14)0.32058 (8)0.0329 (5)
H12A1.12800.44020.31000.039*
H12B0.97120.51810.34480.039*
C130.8657 (3)0.37305 (14)0.35939 (8)0.0267 (4)
C140.8548 (3)0.27739 (13)0.31973 (8)0.0267 (4)
H141.01090.26650.30380.032*
C150.8117 (4)0.19464 (15)0.36767 (9)0.0418 (5)
H15A0.85610.12990.35120.050*
H15B0.65130.19250.38010.050*
C160.9667 (5)0.22585 (15)0.42264 (10)0.0460 (6)
H16A0.89300.21100.46230.055*
H16B1.11260.19080.42090.055*
C171.0028 (4)0.33729 (15)0.41549 (8)0.0307 (4)
C180.6314 (4)0.40438 (18)0.38719 (9)0.0436 (5)
H18A0.65030.46410.41150.065*
H18B0.57390.35190.41350.065*
H18C0.52440.41660.35380.065*
C190.4042 (3)0.42658 (15)0.18101 (9)0.0331 (5)
H19A0.41180.49440.19550.050*
H19B0.34600.38470.21390.050*
H19C0.30380.42270.14540.050*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O30.0995 (15)0.0344 (8)0.0314 (8)−0.0083 (10)−0.0306 (9)−0.0014 (6)
O50.0335 (7)0.0368 (8)0.0328 (7)0.0077 (6)0.0005 (6)−0.0113 (6)
O60.0397 (8)0.0592 (10)0.0482 (8)−0.0219 (9)−0.0106 (7)0.0154 (8)
O170.0437 (8)0.0463 (8)0.0289 (7)0.0028 (8)−0.0082 (7)−0.0058 (6)
C10.0425 (11)0.0251 (9)0.0235 (9)−0.0085 (9)−0.0074 (8)0.0012 (7)
C20.0548 (13)0.0278 (9)0.0247 (9)−0.0095 (10)−0.0092 (10)0.0023 (8)
C30.0461 (12)0.0328 (10)0.0213 (9)−0.0015 (10)−0.0054 (9)−0.0025 (8)
C40.0398 (10)0.0236 (9)0.0260 (9)−0.0050 (9)−0.0069 (8)−0.0041 (7)
C50.0256 (9)0.0230 (9)0.0250 (8)−0.0013 (8)−0.0021 (7)−0.0039 (7)
C60.0417 (11)0.0227 (9)0.0335 (10)−0.0083 (9)−0.0086 (9)−0.0010 (8)
C70.0468 (12)0.0202 (9)0.0330 (10)−0.0055 (9)−0.0082 (9)0.0033 (7)
C80.0257 (9)0.0237 (8)0.0251 (8)−0.0010 (8)−0.0020 (7)0.0016 (7)
C90.0249 (9)0.0215 (8)0.0213 (8)−0.0010 (7)−0.0017 (7)−0.0010 (7)
C100.0249 (9)0.0193 (8)0.0216 (8)−0.0004 (7)−0.0009 (7)−0.0018 (7)
C110.0504 (13)0.0231 (9)0.0262 (9)−0.0037 (9)−0.0092 (9)−0.0002 (7)
C120.0458 (12)0.0289 (9)0.0240 (9)−0.0060 (9)−0.0066 (9)−0.0018 (7)
C130.0293 (9)0.0294 (9)0.0215 (8)0.0035 (8)−0.0006 (8)−0.0011 (7)
C140.0287 (10)0.0256 (9)0.0258 (8)0.0003 (8)−0.0008 (8)0.0008 (7)
C150.0570 (14)0.0325 (11)0.0359 (10)−0.0053 (11)−0.0098 (10)0.0095 (9)
C160.0661 (16)0.0387 (11)0.0332 (10)0.0014 (12)−0.0136 (11)0.0086 (9)
C170.0310 (10)0.0391 (11)0.0220 (9)0.0048 (9)0.0027 (8)−0.0005 (8)
C180.0364 (11)0.0598 (14)0.0346 (10)0.0160 (11)0.0025 (10)−0.0060 (10)
C190.0303 (11)0.0382 (11)0.0306 (9)0.0076 (9)−0.0034 (9)−0.0043 (8)
Geometric parameters (Å, °) top
O3—C31.441 (2)C8—H80.9800
O3—H30.8200C9—C111.539 (2)
O5—C51.444 (2)C9—C101.555 (2)
O5—H50.8200C9—H90.9800
O6—C61.430 (3)C10—C191.535 (3)
O6—H6A0.8200C11—C121.535 (2)
O17—C171.215 (2)C11—H11A0.9700
C1—C21.531 (2)C11—H11B0.9700
C1—C101.538 (2)C12—C131.520 (3)
C1—H1A0.9700C12—H12A0.9700
C1—H1B0.9700C12—H12B0.9700
C2—C31.510 (3)C13—C171.515 (3)
C2—H2A0.9700C13—C141.536 (2)
C2—H2B0.9700C13—C181.543 (3)
C3—C41.518 (3)C14—C151.528 (2)
C3—H3A0.9800C14—H140.9800
C4—C51.537 (2)C15—C161.537 (3)
C4—H4A0.9700C15—H15A0.9700
C4—H4B0.9700C15—H15B0.9700
C5—C61.533 (3)C16—C171.514 (3)
C5—C101.558 (2)C16—H16A0.9700
C6—C71.522 (3)C16—H16B0.9700
C6—H60.9800C18—H18A0.9600
C7—C81.530 (2)C18—H18B0.9600
C7—H7A0.9700C18—H18C0.9600
C7—H7B0.9700C19—H19A0.9600
C8—C141.522 (2)C19—H19B0.9600
C8—C91.544 (2)C19—H19C0.9600
C3—O3—H3109.5C19—C10—C1107.80 (16)
C5—O5—H5109.5C19—C10—C9109.59 (14)
C6—O6—H6A109.5C1—C10—C9111.35 (14)
C2—C1—C10112.67 (15)C19—C10—C5112.05 (14)
C2—C1—H1A109.1C1—C10—C5107.44 (13)
C10—C1—H1A109.1C9—C10—C5108.61 (13)
C2—C1—H1B109.1C12—C11—C9113.91 (15)
C10—C1—H1B109.1C12—C11—H11A108.8
H1A—C1—H1B107.8C9—C11—H11A108.8
C3—C2—C1111.62 (15)C12—C11—H11B108.8
C3—C2—H2A109.3C9—C11—H11B108.8
C1—C2—H2A109.3H11A—C11—H11B107.7
C3—C2—H2B109.3C13—C12—C11109.85 (16)
C1—C2—H2B109.3C13—C12—H12A109.7
H2A—C2—H2B108.0C11—C12—H12A109.7
O3—C3—C2111.65 (16)C13—C12—H12B109.7
O3—C3—C4107.56 (16)C11—C12—H12B109.7
C2—C3—C4112.23 (14)H12A—C12—H12B108.2
O3—C3—H3A108.4C17—C13—C12116.91 (17)
C2—C3—H3A108.4C17—C13—C14101.13 (14)
C4—C3—H3A108.4C12—C13—C14109.33 (14)
C3—C4—C5112.54 (15)C17—C13—C18104.28 (15)
C3—C4—H4A109.1C12—C13—C18111.22 (17)
C5—C4—H4A109.1C14—C13—C18113.69 (16)
C3—C4—H4B109.1C8—C14—C15120.83 (16)
C5—C4—H4B109.1C8—C14—C13112.78 (14)
H4A—C4—H4B107.8C15—C14—C13104.05 (14)
O5—C5—C6106.23 (15)C8—C14—H14106.1
O5—C5—C4107.77 (14)C15—C14—H14106.1
C6—C5—C4112.08 (14)C13—C14—H14106.1
O5—C5—C10106.01 (13)C14—C15—C16102.55 (16)
C6—C5—C10113.17 (13)C14—C15—H15A111.3
C4—C5—C10111.12 (14)C16—C15—H15A111.3
O6—C6—C7106.51 (16)C14—C15—H15B111.3
O6—C6—C5114.67 (17)C16—C15—H15B111.3
C7—C6—C5111.02 (15)H15A—C15—H15B109.2
O6—C6—H6108.1C17—C16—C15105.81 (17)
C7—C6—H6108.1C17—C16—H16A110.6
C5—C6—H6108.1C15—C16—H16A110.6
C6—C7—C8112.96 (15)C17—C16—H16B110.6
C6—C7—H7A109.0C15—C16—H16B110.6
C8—C7—H7A109.0H16A—C16—H16B108.7
C6—C7—H7B109.0O17—C17—C16125.09 (19)
C8—C7—H7B109.0O17—C17—C13126.38 (17)
H7A—C7—H7B107.8C16—C17—C13108.53 (17)
C14—C8—C7111.77 (14)C13—C18—H18A109.5
C14—C8—C9108.37 (14)C13—C18—H18B109.5
C7—C8—C9110.60 (14)H18A—C18—H18B109.5
C14—C8—H8108.7C13—C18—H18C109.5
C7—C8—H8108.7H18A—C18—H18C109.5
C9—C8—H8108.7H18B—C18—H18C109.5
C11—C9—C8112.67 (13)C10—C19—H19A109.5
C11—C9—C10113.30 (14)C10—C19—H19B109.5
C8—C9—C10111.41 (14)H19A—C19—H19B109.5
C11—C9—H9106.3C10—C19—H19C109.5
C8—C9—H9106.3H19A—C19—H19C109.5
C10—C9—H9106.3H19B—C19—H19C109.5
C10—C1—C2—C3−56.4 (2)O5—C5—C10—C159.79 (17)
C1—C2—C3—O3172.65 (17)C6—C5—C10—C1175.84 (15)
C1—C2—C3—C451.8 (2)C4—C5—C10—C1−57.03 (19)
O3—C3—C4—C5−175.47 (15)O5—C5—C10—C9−60.77 (17)
C2—C3—C4—C5−52.3 (2)C6—C5—C10—C955.28 (19)
C3—C4—C5—O5−60.09 (19)C4—C5—C10—C9−177.60 (14)
C3—C4—C5—C6−176.63 (16)C8—C9—C11—C1250.7 (2)
C3—C4—C5—C1055.7 (2)C10—C9—C11—C12178.37 (16)
O5—C5—C6—O6−177.18 (15)C9—C11—C12—C13−52.8 (2)
C4—C5—C6—O6−59.7 (2)C11—C12—C13—C17170.85 (16)
C10—C5—C6—O666.9 (2)C11—C12—C13—C1456.8 (2)
O5—C5—C6—C762.06 (18)C11—C12—C13—C18−69.57 (19)
C4—C5—C6—C7179.52 (15)C7—C8—C14—C15−55.8 (2)
C10—C5—C6—C7−53.9 (2)C9—C8—C14—C15−177.90 (16)
O6—C6—C7—C8−72.2 (2)C7—C8—C14—C13−179.62 (16)
C5—C6—C7—C853.2 (2)C9—C8—C14—C1358.24 (19)
C6—C7—C8—C14−176.03 (16)C17—C13—C14—C8173.72 (15)
C6—C7—C8—C9−55.2 (2)C12—C13—C14—C8−62.4 (2)
C14—C8—C9—C11−51.4 (2)C18—C13—C14—C862.6 (2)
C7—C8—C9—C11−174.26 (16)C17—C13—C14—C1541.03 (18)
C14—C8—C9—C10179.96 (14)C12—C13—C14—C15164.95 (17)
C7—C8—C9—C1057.1 (2)C18—C13—C14—C15−70.1 (2)
C2—C1—C10—C19−62.94 (19)C8—C14—C15—C16−168.04 (17)
C2—C1—C10—C9176.82 (15)C13—C14—C15—C16−40.2 (2)
C2—C1—C10—C558.0 (2)C14—C15—C16—C1723.2 (2)
C11—C9—C10—C19−62.1 (2)C15—C16—C17—O17−177.7 (2)
C8—C9—C10—C1966.23 (18)C15—C16—C17—C132.2 (2)
C11—C9—C10—C157.1 (2)C12—C13—C17—O1734.9 (3)
C8—C9—C10—C1−174.59 (14)C14—C13—C17—O17153.5 (2)
C11—C9—C10—C5175.23 (15)C18—C13—C17—O17−88.3 (2)
C8—C9—C10—C5−56.48 (18)C12—C13—C17—C16−145.00 (19)
O5—C5—C10—C19178.02 (15)C14—C13—C17—C16−26.4 (2)
C6—C5—C10—C19−65.9 (2)C18—C13—C17—C1691.8 (2)
C4—C5—C10—C1961.19 (19)C19—C10—C13—C181.68 (16)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O17i0.822.112.931 (2)175
O5—H5···O3ii0.821.992.8063 (19)171
O6—H6A···O5iii0.822.393.120 (2)148
Symmetry codes: (i) −x+3/2, −y+1, z−1/2; (ii) x+1/2, −y+1/2, −z; (iii) x−1, y, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O17i0.822.112.931 (2)175
O5—H5···O3ii0.821.992.8063 (19)171
O6—H6A···O5iii0.822.393.120 (2)148
Symmetry codes: (i) −x+3/2, −y+1, z−1/2; (ii) x+1/2, −y+1/2, −z; (iii) x−1, y, z.
Acknowledgements top

This work was supported by the Fundação para a Ciência e Tecnologia. We gratefully acknowledge the LCA–UC for a grant of computer time in the Milipeia cluster and Mr Carlos Pereira for help with the analysis of the output of the GAMESS code.

references
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