3α,4α-Ep­oxy-5α-androstan-17β-yl acetate

Andrade, L.C.R.; Paixão, J.A.; de Almeida, M.J.M.; Fernandes Roleira, F.M.; Tavares da Silva, E.J.

doi:10.1107/S160053680900899X

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 65| Part 4| April 2009| Page o814

doi:10.1107/S160053680900899X

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3α,4α-Epoxy-5α-androstan-17β-yl acetate

L. C.R. Andrade,^a J. A. Paixão,^a ^* M.J.M. de Almeida,^a F. M. Fernandes Roleira ^b and E. J. Tavares da Silva ^b

^aCEMDRX, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, P-3004-516 Coimbra, Portugal, and ^bCentro de Estudos Farmacêuticos, Laboratório de Química Farmacêutica, Faculdade de Farmácia, Universidade de Coimbra, P-3000-295 Coimbra, Portugal
^*Correspondence e-mail: jap@pollux.fis.uc.pt

(Received 11 December 2008; accepted 11 March 2009; online 25 March 2009)

The title compound, C₂₁H₃₂O₃, results from modifications of the A and D rings of the aromatase substrate androstenedione. Ring A adopts a conformation between 10β-sofa and 1α,10β half-chair. Rings B and C are in slightly flattened chair conformations. Ring D approaches a 13β-envelope conformation, probably due to the acetoxy substituent, and shows a very short Csp³—Csp³ bond next to the epoxide ring, which is characteristic of 3–4 epoxides. .

Related literature

For the antitumor and anti-aromatase activity of aromatase substrate derivatives, see: Cepa et al. (2005 ). For related structures, see: Paixão et al. (1997 ); Andrade et al. (1997 ). For bond-length data,, see: Allen et al. (1987 ). For asymmetry, pseudo-rotation and puckering parameters, see: Duax & Norton (1975 ); Cremer & Pople (1975 ); Altona et al. (1968 ).

Experimental

Crystal data

C₂₁H₃₂O₃
M_r = 332.47
Orthorhombic, P 2₁ 2₁ 2₁
a = 6.2760 (2) Å
b = 11.7272 (19) Å
c = 25.0888 (9) Å
V = 1846.5 (3) Å³
Z = 4
Cu Kα radiation
μ = 0.61 mm⁻¹
T = 293 K
0.36 × 0.20 × 0.12 mm

Data collection

Enraf–Nonius MACH-3 diffractometer
Absorption correction: none
2661 measured reflections
2146 independent reflections
1715 reflections with I > 2σ(I)
R_int = 0.050
3 standard reflections every 300 reflections intensity decay: 1.3%

Refinement

R[F² > 2σ(F²)] = 0.044
wR(F²) = 0.135
S = 1.03
2146 reflections
221 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.18 e Å⁻³
Absolute structure: Flack (1983 ), with 0 Friedel pairs
Flack parameter: −0.1 (5)

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ); cell refinement: CAD-4 Software; data reduction: HELENA (Spek, 1997 ) and PLATON Spek (2009 ); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPII (Johnson, 1976 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053680900899X/kp2201sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053680900899X/kp2201Isup2.hkl

checkCIF report

Comment top

Recently, a new series of steroids, which result from modifications in the A– and D-rings of the aromatase substrate, androstenedione, were designed, synthesized and evaluated for their anti-tumour and anti-aromatase activity (Cepa et al., 2005). The researches have considered three main structural features for the drug-enzyme interactions, namely, the planarity of the A-ring, the 5α-stereochemistry and the integrity of the cyclopentanone D-ring. In the present work, we are focused on the effect of some refined modifications in the original C–17 carbonyl group in the D-ring of steroids in enzyme inhibition. This study is a contribution to the understanding of the role of the D-ring substitution pattern and its structure in the inhibition of aromatase. Under this project, the title compound (I) was synthesized. In order to establish the conformation of (I), the X-ray structure was determined (Fig. 1). Atomic distances are within expected values (Allen et al., 1987) except for the C2–C3 bond which is much shorter [1.482 (5) Å] than the determined average value for Csp³–Csp³ bond lengths in the molecule [1.532 (16) Å]. This is probably characteristic of 3–4 epoxides since similar values [1.494 (4) and 1.484 (5) Å] were obtained for two related structures (Paixão et al., 1997 and Andrade et al., 1997). The ring A [C1→C10] is severely distorted assuming a conformation intermediate between10β-sofa and 1α,10β-half chair [asymmetry parametres (Duax & Norton, 1975): ΔC_s(3)=11.4 (3), ΔC₂(3,4)=14.8 (4) and ΔC₂(1,2)=53.5 (4)°]. Rings B [C5→C10] and C [C8→-C14] have slightly flattened chair conformations evidenced by the average values of their torsion angles [56 (2)° for both]. The five member ring D [C13→C17] assumes a conformation intermediate between 13β-envelope and 13β,14α-half chair, probably due to the acetoxy substituent [puckering parametres (Cremer & Pople, 1975) q₂=0.477 (3)Å and ϕ₂=188.6 (4)°; pseudo-rotation (Altona et al., 1968) and asymmetry parameters (Duax & Norton, 1975): Δ=18.8 (4), ϕ_m=48.5 (2), ΔC_s(13)=8.9 (3), ΔC₂(13,14)=12.7 (3) and ΔC_s(14)=27.2 (3)°). The distance between terminal O atoms is 11.204 (3)°. A pseudo-torsion angle C19–C10···C13–C18 of 1.6 (2) ° evidences that the molecule is not twisted. The dihedral angle between the least-squares plane of the four non-H atoms of the acetate group and that of ring D is 65.04 (17)°. The crystal packing is determined by van der Waals interactions.

Related literature top

For the anti-tumor and anti-aromatase activity of aromatase substrate derivatives, see: Cepa et al. (2005). For related structures, see: Paixão et al. (1997); Andrade et al. (1997). For bond-length data,, see: Allen et al. (1987). For aymmetry, pseudo-rotation and puckering parameters, see: Duax & Norton (1975); Cremer & Pople (1975); Altona et al. (1968).

Experimental top

To a solution of 5α-androst-3-en-17β-yl acetate (308 mg, 0.97 mmol) in methylene chloride (5.0 ml), a solution of performic acid (0.15 ml of HCOOH 98–100% and 0.4 ml of H₂O₂ 35%) was added and the reaction stirred overnight until complete transformation of starting material. Methylene chloride (150 ml) was added and the organic layer was washed with 10% NaHCO₃ (2x100 ml) and water (4x100 ml) and then dried over anhydrous MgSO₄. After filtration and solvent evaporation to dryness, the almost pure title compound was obtained as a white solid (296 mg, 92%). Column chromatography (silica gel 60 with 95: 5 to 95: 10 mixtures of petroleum ether 40–60 °C and ethyl acetate) or crystallization from ethyl acetate n–hexane, yielded analytical samples: Mp 461–463 K; IR ν_max(KBr) cm^-1: 1732 (C?O); ¹H NMR (300 MHz, CDCl₃) δ: 0.77 (3H, s, 18-H₃)*, 0.78 (3H, s, 19-H₃)*, 2.03 (3H, s, CH₃COO), 2.69 (1H, d, J₄_β_,5_α=3.9, 4β-H), 3.16 (1H, dd, J₃_β_,2_α=3.0, J₃_β_,2_β=3.0, 3β-H), 4.58 (1H, dd, J₁₇_α_,16_α=9.0, J₁₇_α_,16_β=7.8, 17α-H); ¹³C NMR (75.6 MHz, DMSO-d₆) δ: 12.1 (C-19), 13.4 (C-18), 20.7, 21.2, 21.3, 23.4, 26.6, 27.5, 30.4, 31.4, 34.1, 35.1, 36.8, 42.6, 46.7, 50.5 52.1**, 52.5 (C-4)**, 55.8 (C-3), 82.7 (C-17); 171.2 (C?O); EIMS m/z 332 (M⁺, 87%). *,** Signals may be interchangeable.

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: HELENA (Spek, 1997) and PLATON Spek (2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

Fig. 1. ORTEPII (Johnson, 1976) of (I). Displacement ellipsoids are drawn at the 50% probability level.

3α,4α-Epoxy-5α-androstan-17β-yl acetate top

Crystal data top

C₂₁H₃₂O₃	D_x = 1.196 Mg m⁻³
M_r = 332.47	Cu Kα radiation, λ = 1.54180 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 25 reflections
a = 6.2760 (2) Å	θ = 13.4–28.2°
b = 11.7272 (19) Å	µ = 0.61 mm⁻¹
c = 25.0888 (9) Å	T = 293 K
V = 1846.5 (3) Å³	Truncated pyramid, colourless
Z = 4	0.36 × 0.20 × 0.12 mm
F(000) = 728

Data collection top

Enraf–Nonius MACH-3 diffractometer	R_int = 0.050
Radiation source: fine-focus sealed tube	θ_max = 73.8°, θ_min = 3.5°
Graphite monochromator	h = −6→7
Profile data from ω–2θ scans	k = 0→14
2661 measured reflections	l = 0→31
2146 independent reflections	3 standard reflections every 300 reflections
1715 reflections with I > 2σ(I)	intensity decay: 1.3%

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.044	w = 1/[σ²(F_o²) + (0.0886P)² + 0.2976P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.135	(Δ/σ)_max = 0.004
S = 1.03	Δρ_max = 0.23 e Å⁻³
2146 reflections	Δρ_min = −0.18 e Å⁻³
221 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0030 (6)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 0 Friedel pairs
Secondary atom site location: difference Fourier map	Absolute structure parameter: −0.1 (5)

Crystal data top

C₂₁H₃₂O₃	V = 1846.5 (3) Å³
M_r = 332.47	Z = 4
Orthorhombic, P2₁2₁2₁	Cu Kα radiation
a = 6.2760 (2) Å	µ = 0.61 mm⁻¹
b = 11.7272 (19) Å	T = 293 K
c = 25.0888 (9) Å	0.36 × 0.20 × 0.12 mm

Data collection top

Enraf–Nonius MACH-3 diffractometer	R_int = 0.050
2661 measured reflections	3 standard reflections every 300 reflections
2146 independent reflections	intensity decay: 1.3%
1715 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.044	H-atom parameters constrained
wR(F²) = 0.135	Δρ_max = 0.23 e Å⁻³
S = 1.03	Δρ_min = −0.18 e Å⁻³
2146 reflections	Absolute structure: Flack (1983), 0 Friedel pairs
221 parameters	Absolute structure parameter: −0.1 (5)
0 restraints

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	U_iso*/U_eq
O3	0.6940 (5)	0.54519 (19)	0.50056 (8)	0.0627 (7)
O17A	1.1217 (4)	0.38347 (16)	0.12529 (7)	0.0536 (6)
O17B	1.2588 (5)	0.52535 (19)	0.07703 (9)	0.0669 (7)
C1	0.9480 (5)	0.3851 (3)	0.42667 (10)	0.0481 (7)
H1A	1.0406	0.3237	0.4150	0.058*
H1B	1.0340	0.4535	0.4298	0.058*
C2	0.8561 (6)	0.3552 (3)	0.48152 (11)	0.0565 (8)
H2A	0.8167	0.2752	0.4816	0.068*
H2B	0.9667	0.3655	0.5081	0.068*
C3	0.6677 (6)	0.4235 (3)	0.49734 (11)	0.0529 (8)
H3	0.5753	0.3892	0.5244	0.063*
C4	0.5617 (5)	0.4987 (3)	0.45865 (10)	0.0480 (7)
H4	0.4075	0.5083	0.4630	0.058*
C5	0.6477 (5)	0.5113 (2)	0.40261 (9)	0.0381 (6)
H5	0.7500	0.5744	0.4038	0.046*
C6	0.4757 (5)	0.5465 (2)	0.36317 (10)	0.0436 (6)
H6A	0.4018	0.6134	0.3763	0.052*
H6B	0.3726	0.4854	0.3594	0.052*
C7	0.5761 (5)	0.5727 (2)	0.30914 (10)	0.0431 (6)
H7A	0.6666	0.6393	0.3124	0.052*
H7B	0.4643	0.5904	0.2837	0.052*
C8	0.7080 (4)	0.4730 (2)	0.28806 (9)	0.0338 (5)
H8	0.6114	0.4090	0.2812	0.041*
C9	0.8761 (4)	0.4339 (2)	0.32915 (9)	0.0340 (5)
H9	0.9703	0.4993	0.3352	0.041*
C10	0.7745 (4)	0.4048 (2)	0.38411 (9)	0.0352 (5)
C11	1.0165 (4)	0.3385 (2)	0.30642 (10)	0.0407 (6)
H11A	0.9306	0.2704	0.3018	0.049*
H11B	1.1282	0.3209	0.3318	0.049*
C12	1.1185 (5)	0.3702 (3)	0.25284 (10)	0.0429 (6)
H12A	1.2172	0.4329	0.2581	0.051*
H12B	1.1983	0.3056	0.2393	0.051*
C13	0.9502 (4)	0.4047 (2)	0.21221 (9)	0.0355 (6)
C14	0.8196 (4)	0.5035 (2)	0.23599 (9)	0.0359 (6)
H14	0.9218	0.5639	0.2446	0.043*
C15	0.6882 (5)	0.5471 (3)	0.18884 (10)	0.0501 (7)
H15A	0.6508	0.6267	0.1935	0.060*
H15B	0.5587	0.5028	0.1846	0.060*
C16	0.8385 (5)	0.5311 (3)	0.14039 (10)	0.0496 (7)
H16A	0.7686	0.4879	0.1125	0.060*
H16B	0.8819	0.6044	0.1261	0.060*
C17	1.0306 (5)	0.4658 (2)	0.16230 (10)	0.0427 (6)
H17	1.1411	0.5206	0.1726	0.051*
C17A	1.2337 (5)	0.4256 (3)	0.08422 (11)	0.0496 (7)
C17B	1.3214 (8)	0.3334 (3)	0.05006 (14)	0.0751 (12)
H17A	1.4147	0.3659	0.0238	0.090*
H17B	1.2066	0.2943	0.0326	0.090*
H17C	1.3996	0.2805	0.0717	0.090*
C18	0.8135 (6)	0.3021 (2)	0.19638 (12)	0.0507 (7)
H18A	0.9021	0.2450	0.1802	0.061*
H18B	0.7062	0.3258	0.1715	0.061*
H18C	0.7464	0.2710	0.2275	0.061*
C19	0.6299 (5)	0.2992 (2)	0.38040 (11)	0.0433 (6)
H19A	0.7163	0.2318	0.3787	0.052*
H19B	0.5435	0.3043	0.3489	0.052*
H19C	0.5398	0.2957	0.4113	0.052*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O3	0.0852 (18)	0.0598 (13)	0.0431 (10)	−0.0031 (14)	−0.0105 (12)	−0.0122 (10)
O17A	0.0745 (15)	0.0438 (10)	0.0426 (10)	0.0005 (11)	0.0153 (11)	−0.0037 (9)
O17B	0.0881 (18)	0.0506 (12)	0.0620 (13)	−0.0109 (14)	0.0256 (14)	0.0019 (11)
C1	0.0472 (15)	0.0599 (17)	0.0371 (13)	0.0056 (15)	−0.0072 (13)	0.0053 (13)
C2	0.066 (2)	0.0656 (19)	0.0380 (13)	0.0059 (18)	−0.0084 (15)	0.0076 (13)
C3	0.066 (2)	0.0574 (17)	0.0348 (13)	−0.0033 (17)	0.0006 (14)	−0.0005 (12)
C4	0.0508 (16)	0.0553 (16)	0.0378 (13)	0.0003 (15)	0.0003 (13)	−0.0072 (12)
C5	0.0395 (14)	0.0380 (13)	0.0368 (12)	−0.0002 (12)	−0.0013 (11)	0.0000 (10)
C6	0.0413 (14)	0.0473 (14)	0.0421 (13)	0.0122 (13)	0.0042 (12)	0.0019 (11)
C7	0.0446 (15)	0.0449 (14)	0.0397 (13)	0.0113 (13)	0.0003 (12)	0.0080 (11)
C8	0.0317 (11)	0.0353 (12)	0.0343 (11)	0.0004 (11)	−0.0021 (10)	0.0025 (9)
C9	0.0315 (11)	0.0355 (12)	0.0349 (11)	−0.0004 (11)	−0.0032 (10)	0.0012 (10)
C10	0.0368 (13)	0.0347 (12)	0.0340 (11)	0.0015 (12)	−0.0027 (11)	0.0032 (9)
C11	0.0394 (13)	0.0445 (14)	0.0381 (12)	0.0095 (13)	−0.0041 (11)	0.0034 (11)
C12	0.0380 (14)	0.0496 (15)	0.0411 (13)	0.0068 (13)	0.0014 (12)	−0.0026 (11)
C13	0.0383 (13)	0.0330 (12)	0.0351 (12)	−0.0018 (11)	−0.0009 (11)	−0.0022 (10)
C14	0.0362 (13)	0.0359 (12)	0.0357 (12)	0.0005 (11)	−0.0028 (11)	0.0024 (10)
C15	0.0516 (16)	0.0585 (17)	0.0401 (13)	0.0086 (15)	−0.0038 (14)	0.0099 (13)
C16	0.0633 (19)	0.0504 (15)	0.0351 (12)	0.0043 (16)	−0.0023 (13)	0.0052 (12)
C17	0.0508 (15)	0.0402 (13)	0.0372 (12)	−0.0050 (14)	0.0065 (12)	−0.0037 (11)
C17A	0.0558 (18)	0.0517 (16)	0.0414 (13)	−0.0010 (15)	0.0088 (14)	−0.0001 (12)
C17B	0.110 (3)	0.056 (2)	0.0590 (19)	0.011 (2)	0.030 (2)	−0.0007 (16)
C18	0.0618 (19)	0.0430 (14)	0.0474 (15)	−0.0150 (15)	−0.0002 (15)	−0.0022 (12)
C19	0.0489 (15)	0.0384 (13)	0.0427 (13)	−0.0039 (13)	0.0024 (13)	0.0039 (11)

Geometric parameters (Å, º) top

O3—C3	1.439 (4)	C9—H9	0.9800
O3—C4	1.447 (3)	C10—C19	1.537 (4)
O17A—C17A	1.342 (3)	C11—C12	1.535 (4)
O17A—C17	1.457 (3)	C11—H11A	0.9700
O17B—C17A	1.194 (4)	C11—H11B	0.9700
C1—C2	1.533 (4)	C12—C13	1.523 (4)
C1—C10	1.543 (4)	C12—H12A	0.9700
C1—H1A	0.9700	C12—H12B	0.9700
C1—H1B	0.9700	C13—C17	1.528 (3)
C2—C3	1.482 (5)	C13—C18	1.531 (4)
C2—H2A	0.9700	C13—C14	1.539 (4)
C2—H2B	0.9700	C14—C15	1.530 (3)
C3—C4	1.471 (4)	C14—H14	0.9800
C3—H3	0.9800	C15—C16	1.550 (4)
C4—C5	1.513 (4)	C15—H15A	0.9700
C4—H4	0.9800	C15—H15B	0.9700
C5—C6	1.521 (4)	C16—C17	1.530 (4)
C5—C10	1.553 (4)	C16—H16A	0.9700
C5—H5	0.9800	C16—H16B	0.9700
C6—C7	1.526 (4)	C17—H17	0.9800
C6—H6A	0.9700	C17A—C17B	1.485 (4)
C6—H6B	0.9700	C17B—H17A	0.9600
C7—C8	1.526 (4)	C17B—H17B	0.9600
C7—H7A	0.9700	C17B—H17C	0.9600
C7—H7B	0.9700	C18—H18A	0.9600
C8—C14	1.525 (3)	C18—H18B	0.9600
C8—C9	1.545 (3)	C18—H18C	0.9600
C8—H8	0.9800	C19—H19A	0.9600
C9—C11	1.534 (4)	C19—H19B	0.9600
C9—C10	1.557 (3)	C19—H19C	0.9600

C3—O3—C4	61.3 (2)	C9—C11—H11A	109.0
C17A—O17A—C17	116.8 (2)	C12—C11—H11A	109.0
C2—C1—C10	112.9 (3)	C9—C11—H11B	109.0
C2—C1—H1A	109.0	C12—C11—H11B	109.0
C10—C1—H1A	109.0	H11A—C11—H11B	107.8
C2—C1—H1B	109.0	C13—C12—C11	111.2 (2)
C10—C1—H1B	109.0	C13—C12—H12A	109.4
H1A—C1—H1B	107.8	C11—C12—H12A	109.4
C3—C2—C1	114.6 (3)	C13—C12—H12B	109.4
C3—C2—H2A	108.6	C11—C12—H12B	109.4
C1—C2—H2A	108.6	H12A—C12—H12B	108.0
C3—C2—H2B	108.6	C12—C13—C17	116.4 (2)
C1—C2—H2B	108.6	C12—C13—C18	110.7 (2)
H2A—C2—H2B	107.6	C17—C13—C18	110.0 (2)
O3—C3—C4	59.62 (19)	C12—C13—C14	108.0 (2)
O3—C3—C2	117.4 (3)	C17—C13—C14	98.1 (2)
C4—C3—C2	120.6 (3)	C18—C13—C14	113.2 (2)
O3—C3—H3	115.8	C8—C14—C15	119.5 (2)
C4—C3—H3	115.8	C8—C14—C13	113.7 (2)
C2—C3—H3	115.8	C15—C14—C13	103.8 (2)
O3—C4—C3	59.08 (18)	C8—C14—H14	106.3
O3—C4—C5	115.7 (3)	C15—C14—H14	106.3
C3—C4—C5	120.7 (3)	C13—C14—H14	106.3
O3—C4—H4	116.3	C14—C15—C16	103.8 (2)
C3—C4—H4	116.3	C14—C15—H15A	111.0
C5—C4—H4	116.3	C16—C15—H15A	111.0
C4—C5—C6	112.2 (2)	C14—C15—H15B	111.0
C4—C5—C10	112.4 (2)	C16—C15—H15B	111.0
C6—C5—C10	112.8 (2)	H15A—C15—H15B	109.0
C4—C5—H5	106.3	C17—C16—C15	105.0 (2)
C6—C5—H5	106.3	C17—C16—H16A	110.8
C10—C5—H5	106.3	C15—C16—H16A	110.8
C5—C6—C7	109.8 (2)	C17—C16—H16B	110.8
C5—C6—H6A	109.7	C15—C16—H16B	110.8
C7—C6—H6A	109.7	H16A—C16—H16B	108.8
C5—C6—H6B	109.7	O17A—C17—C13	109.9 (2)
C7—C6—H6B	109.7	O17A—C17—C16	114.3 (2)
H6A—C6—H6B	108.2	C13—C17—C16	105.6 (2)
C6—C7—C8	112.2 (2)	O17A—C17—H17	109.0
C6—C7—H7A	109.2	C13—C17—H17	109.0
C8—C7—H7A	109.2	C16—C17—H17	109.0
C6—C7—H7B	109.2	O17B—C17A—O17A	123.1 (3)
C8—C7—H7B	109.2	O17B—C17A—C17B	125.2 (3)
H7A—C7—H7B	107.9	O17A—C17A—C17B	111.7 (3)
C14—C8—C7	111.5 (2)	C17A—C17B—H17A	109.5
C14—C8—C9	109.1 (2)	C17A—C17B—H17B	109.5
C7—C8—C9	111.5 (2)	H17A—C17B—H17B	109.5
C14—C8—H8	108.2	C17A—C17B—H17C	109.5
C7—C8—H8	108.2	H17A—C17B—H17C	109.5
C9—C8—H8	108.2	H17B—C17B—H17C	109.5
C11—C9—C8	111.17 (19)	C13—C18—H18A	109.5
C11—C9—C10	113.9 (2)	C13—C18—H18B	109.5
C8—C9—C10	112.1 (2)	H18A—C18—H18B	109.5
C11—C9—H9	106.4	C13—C18—H18C	109.5
C8—C9—H9	106.4	H18A—C18—H18C	109.5
C10—C9—H9	106.4	H18B—C18—H18C	109.5
C19—C10—C1	109.8 (2)	C10—C19—H19A	109.5
C19—C10—C5	111.3 (2)	C10—C19—H19B	109.5
C1—C10—C5	106.0 (2)	H19A—C19—H19B	109.5
C19—C10—C9	111.4 (2)	C10—C19—H19C	109.5
C1—C10—C9	110.9 (2)	H19A—C19—H19C	109.5
C5—C10—C9	107.36 (19)	H19B—C19—H19C	109.5
C9—C11—C12	112.8 (2)

C10—C1—C2—C3	−42.1 (4)	C11—C9—C10—C5	177.3 (2)
C4—O3—C3—C2	111.1 (3)	C8—C9—C10—C5	−55.4 (3)
C1—C2—C3—O3	−59.3 (4)	C8—C9—C11—C12	53.4 (3)
C1—C2—C3—C4	9.8 (4)	C10—C9—C11—C12	−178.8 (2)
C3—O3—C4—C5	−111.8 (3)	C9—C11—C12—C13	−55.7 (3)
C2—C3—C4—O3	−105.8 (4)	C11—C12—C13—C17	165.4 (2)
O3—C3—C4—C5	103.4 (3)	C11—C12—C13—C18	−68.1 (3)
C2—C3—C4—C5	−2.4 (5)	C11—C12—C13—C14	56.4 (3)
O3—C4—C5—C6	−137.4 (3)	C7—C8—C14—C15	−55.3 (3)
C3—C4—C5—C6	154.8 (3)	C9—C8—C14—C15	−178.9 (2)
O3—C4—C5—C10	94.2 (3)	C7—C8—C14—C13	−178.4 (2)
C3—C4—C5—C10	26.4 (4)	C9—C8—C14—C13	57.9 (3)
C4—C5—C6—C7	172.8 (2)	C12—C13—C14—C8	−59.6 (3)
C10—C5—C6—C7	−59.0 (3)	C17—C13—C14—C8	179.2 (2)
C5—C6—C7—C8	55.4 (3)	C18—C13—C14—C8	63.4 (3)
C6—C7—C8—C14	−176.0 (2)	C12—C13—C14—C15	169.0 (2)
C6—C7—C8—C9	−53.8 (3)	C17—C13—C14—C15	47.8 (2)
C14—C8—C9—C11	−53.0 (3)	C18—C13—C14—C15	−68.0 (3)
C7—C8—C9—C11	−176.7 (2)	C8—C14—C15—C16	−162.5 (2)
C14—C8—C9—C10	178.26 (19)	C13—C14—C15—C16	−34.7 (3)
C7—C8—C9—C10	54.6 (3)	C14—C15—C16—C17	7.2 (3)
C2—C1—C10—C19	−56.1 (3)	C17A—O17A—C17—C13	−168.1 (2)
C2—C1—C10—C5	64.3 (3)	C17A—O17A—C17—C16	73.4 (3)
C2—C1—C10—C9	−179.5 (2)	C12—C13—C17—O17A	78.1 (3)
C4—C5—C10—C19	64.4 (3)	C18—C13—C17—O17A	−48.7 (3)
C6—C5—C10—C19	−63.7 (3)	C14—C13—C17—O17A	−167.0 (2)
C4—C5—C10—C1	−54.9 (3)	C12—C13—C17—C16	−158.1 (2)
C6—C5—C10—C1	177.0 (2)	C18—C13—C17—C16	75.1 (3)
C4—C5—C10—C9	−173.4 (2)	C14—C13—C17—C16	−43.3 (2)
C6—C5—C10—C9	58.5 (3)	C15—C16—C17—O17A	144.0 (3)
C11—C9—C10—C19	−60.6 (3)	C15—C16—C17—C13	23.0 (3)
C8—C9—C10—C19	66.7 (3)	C17—O17A—C17A—O17B	−0.7 (5)
C11—C9—C10—C1	62.0 (3)	C17—O17A—C17A—C17B	178.9 (3)
C8—C9—C10—C1	−170.7 (2)	C19—C10—C13—C18	1.6 (2)

Experimental details

Crystal data
Chemical formula	C₂₁H₃₂O₃
M_r	332.47
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	293
a, b, c (Å)	6.2760 (2), 11.7272 (19), 25.0888 (9)
V (Å³)	1846.5 (3)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	0.61
Crystal size (mm)	0.36 × 0.20 × 0.12

Data collection
Diffractometer	Enraf–Nonius MACH-3 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	2661, 2146, 1715
R_int	0.050
(sin θ/λ)_max (Å⁻¹)	0.623

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.135, 1.03
No. of reflections	2146
No. of parameters	221
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.23, −0.18
Absolute structure	Flack (1983), 0 Friedel pairs
Absolute structure parameter	−0.1 (5)

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), HELENA (Spek, 1997) and PLATON Spek (2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEPII (Johnson, 1976).

Acknowledgements

This work was supported by Fundação para a Ciência e Tecnologia.

References

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