5[alpha]-Androst-3-en-17-one oxime

The title compound, C₁₉H₂₉NO, is a C17-oxime derivative of a potent aromatase inhibitor, which surprisingly has been found to have no inhibitory power. It crystallizes with two independent mol­ecules in the asymmetric unit. C=N-O-H...N hydrogen bonds link pairs of mol­ecules to form dimers almost parallel to the bc plane. Cohesion of the structure is also due to another three C-H...O hydrogen bonds directed along the a axis. This hydrogen-bonding scheme can be correlated to the almost complete loss of inhibitory power of the title compound.

S1. Comment

Following on from our previous work focused on the structure–activity relationships (SAR) of new steroidal aromatase inhibitors (Cepa et al., 2005), several D-ring derivatives of the potent aromatase inhibitor 5α-androst-3-en-17-one (structural studies by Paixão et al., 2001) have been recently prepared and evaluated.

The title compound, (I) (Fig. 1), a C17 oxime derivative, has almost zero inhibitory activity. Hence, it was important, from the point of view of SAR studies, to understand this change of behaviour. X-ray studies indicate that this compound crystallizes with two independent molecules which have almost identical geometry. The internal degree of structural similarity between the two molecules (Kálmán et al., 1991) can be inferred from the values I_D⁽²⁴⁾ (distances)= 99.0% and I_D⁽²³⁾ (valency angles)= 99.7%. Ring bond lengths and angles are within expected values (Allen et al., 1987).

Due to the C═C double bond, ring A adopts a conformation intermediate between 10β-sofa and 1,10-half chair [asymmetry parameters (Duax & Norton, 1975): ΔC_s(3)=10.9 (6) and 12.1 (5), ΔC₂(3,4)=14.3 (7) and 12.4 (7), and ΔC₂(1,2)=51.2 (7) and 50.2 (7)°, respectively, for molecules 1 and 2; puckering parameters (Cremer & Pople, 1975), calculated using the atom sequence C1—C10: q₂=0.387 (5) and 0.380 (5) Å, and ϕ₂= 313.1 (7) and 315.1 (8)°, respectively, for molecules 1 and 2]. Rings B and C have slightly flattened chair conformations. The five membered D-ring adopts a 14α-envelope conformation, slightly distorted towards 13β,14α-half chair [pseudo-rotation (Altona et al., 1968) and asymmetry parameters (Duax & Norton, 1975): Δ=–22.0 (5) and –23.5 (6), ϕ_m=43.6 (2) and 43.0 (2), ΔC_s(14)=6.2 (4) and 5.5 (4), and ΔC₂(13,14)=13.2 (4) and 13.8 (4) °, for molecules 1 and 2]. Due to the existence of only trans ring junctions, both molecules in the asymmetric unit have an almost planar distribution of the ring atoms (r.m.s. deviation 0.2466 and 0.2505, respectively, for molecules 1 and 2), with the planes being almost parallel to each other [angle between planes 4.50 (4)°].

The oxime moiety of both molecules lies on the plane of the D-ring 14α-envelope, as evidenced by the r.m.s. deviation of C13,C15—C17,O1,N1 of 0.0430 and 0.0384 for molecules 1 and 2, respectively. Two strong O—H···N hydrogen bonds lead to a crystal packing built up of dimers, with a six-membered ring O1—H1···N2—O2—H2···N1 (Fig. 2). These hydrogen bonds, in which the O atom acts as a donor, are almost parallel with the c axis. There are three additional C—H···O hydrogen bonds linking molecules along the a axis (Fig. 3), in which the same O atoms act as acceptors. The oxime C—N and N—O bond lengths are slightly smaller and significantly larger, respectively, than the values reported by Allen et al. (1987). These differences may be due to the special features of oxime moieties and their involvement in hydrogen bonds. In fact, the values determined fit well with the work of Jerslev (1983), who studied the correlations between these bond lengths in several oximes.

According to his work, the values obtained in the present study imply a certain degree of conjugation between the oxime moiety and the D-ring electronic distribution. Following Bertolasi et al. (1982), the large values obtained for the N—O bonds can be further related to the multiple hydrogen bonds in which the oxime group participates. The hydrogen bonding scheme determined in this study is, eventually, responsible for the almost total loss of aromatase inhibition behaviour. In fact, by replacing the C17 ketone with the C17 oxime group, the dual acceptor/donor hydrogen-bonding ability of this group can probably destabilize the structure of the receptor by hydrogen bonding to specific residues (Cepa et al., 2008).

Related literature

For related literature, see: Allen et al. (1987); Altona et al. (1968); Bertolasi et al. (1982); Cepa et al. (2005, 2008); Cremer & Pople (1975); Duax & Norton (1975); Jerslev (1983); Kálmán et al. (1991); Paixão, Andrade, de Almeida, Tavares da Silva, Fernandes Roleira, Sá e Melo & Campos Neves (2001).

S2. Experimental

To a solution of 5α-androst-3-en-17-one (150 mg, 0.55 mmol) in methanol (7.0 ml), hydroxylamine hydrochloride (49.2 mg, 0.7 mmol) and CH₃COONa.3H₂O (90 mg, 0.66 mmol) were added. The reaction was stirred at 313 K for 5 h until all the starting material had been consumed. After addition of water (50 ml), the methanol was evaporated and the aqueous phase was extracted with methylene chloride (100 ml). The organic layer was then washed with NaHCO₃ 10% (2×50 ml), water (3×100 ml), dried over MgSO₄, filtered and evaporated to dryness yielding 133.7 mg (84%) of the title oxime. Mp_{(cyclohexane)} 432–434 K; IR ν_max(KBr) cm^-1: 3281 (O–H), 3013 (? C–H); ¹H NMR (300 MHz, DMSO-d₆) δ: 0.75 (3H, s, 19-H₃), 0.82 (3H, s, 18-H₃), 5.27 (1H, ddd, J_4,3=9.5, J_4,5α=4.5, J_4,2α=2.5, 4-H), 5.54 (1H, ddd, J_3,4=9.5, J_3,2β=6.1, J_3,2α=3.1, 3-H), 10.04 (1H, s, NOH); ¹³C NMR (75.6 MHz, DMSO-d₆) δ: 11.7 (C19), 17.3 (C18), 20.2, 22.7, 23.0, 24.7, 26.8, 31.0, 33.5, 34.3, 34.5, 34.6, 43.3, 45.3, (C5), 52.9, 53.5, 125.3, (C3), 131.0 (C4), 167.9 (C17); ESI m/z 288.2 (M+H, 100%).

S3. Refinement

All H atoms were refined as riding on their parent atoms using SHELXL97 (Sheldrick, 2008). The absolute configuration was not determined from the X-ray data but was known from the synthesis route. Friedel pairs were merged before refinement. The structure contains small solvent accessible voids of 35 ų (Spek, 2003). No residual density ws found there.

Computing details

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: PLATON/HELENA (Spek, 2003); 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

	Fig. 1. ORTEPII (Johnson, 1976) plot of the title compound. Displacement ellipsoids are drawn at the 50% level.
	Fig. 2. View of the unit cell parallel to the bc plane showing the dimers, with the six-membered rings O1—H1···N2—O2—H2···N1.
	Fig. 3. View of the unit cell along the a axis showing the three C—H···O hydrogen bonds, linking molecules.

5α-Androst-3-en-17-one oxime

Crystal data

C19H29NO	F(000) = 632
Mr = 287.43	Dx = 1.098 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54180 Å
a = 6.3510 (12) Å	Cell parameters from 25 reflections
b = 42.306 (6) Å	θ = 8.0–31.9°
c = 7.1764 (6) Å	µ = 0.51 mm^−1
β = 115.651 (13)°	T = 293 K
V = 1738.2 (5) Å^3	Prism, colourless
Z = 4	0.48 × 0.24 × 0.24 mm

Data collection

Enraf–Nonius MACH-3 diffractometer	Rint = 0.016
Radiation source: fine-focus sealed tube	θmax = 72.5°, θmin = 4.2°
Graphite monochromator	h = 0→7
profile data from ω–2θ scans	k = −15→52
3820 measured reflections	l = −8→7
3472 independent reflections	3 standard reflections every 240 min
2868 reflections with I > 2σ(I)	intensity decay: 4.9%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.042	H-atom parameters constrained
wR(F^2) = 0.133	w = 1/[σ^2(Fo^2) + (0.0733P)^2 + 0.204P] where P = (Fo^2 + 2Fc^2)/3
S = 1.08	(Δ/σ)max < 0.001
3472 reflections	Δρmax = 0.16 e Å^−3
386 parameters	Δρmin = −0.13 e Å^−3
1 restraint	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0032 (5)

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 (Ų)

	x	y	z	Uiso*/Ueq
N1	0.5622 (5)	0.75922 (6)	0.6623 (4)	0.0639 (6)
O1	0.5251 (5)	0.79170 (6)	0.6116 (4)	0.0770 (7)
H1	0.5734	0.8022	0.7181	0.115*
C1	0.1888 (8)	0.59646 (9)	0.6761 (6)	0.0800 (10)
H1A	0.3252	0.6009	0.8042	0.096*
H1B	0.0578	0.6077	0.6800	0.096*
C2	0.1383 (10)	0.56117 (11)	0.6638 (7)	0.0986 (13)
H2A	0.2848	0.5497	0.7161	0.118*
H2B	0.0618	0.5562	0.7515	0.118*
C3	−0.0116 (9)	0.55053 (11)	0.4502 (8)	0.0963 (13)
H3	−0.0679	0.5299	0.4305	0.116*
C4	−0.0689 (8)	0.56874 (10)	0.2876 (7)	0.0871 (11)
H4	−0.1615	0.5602	0.1584	0.105*
C5	0.0056 (6)	0.60240 (8)	0.2975 (5)	0.0689 (8)
H5	−0.1167	0.6150	0.3107	0.083*
C6	0.0211 (7)	0.61436 (8)	0.1051 (5)	0.0793 (10)
H6A	−0.1224	0.6094	−0.0154	0.095*
H6B	0.1488	0.6039	0.0904	0.095*
C7	0.0606 (6)	0.64983 (8)	0.1171 (5)	0.0717 (9)
H7A	−0.0766	0.6603	0.1141	0.086*
H7B	0.0808	0.6567	−0.0031	0.086*
C8	0.2745 (5)	0.65975 (7)	0.3127 (4)	0.0551 (6)
H8	0.4147	0.6520	0.3027	0.066*
C9	0.2685 (5)	0.64534 (7)	0.5088 (4)	0.0548 (6)
H9	0.1300	0.6543	0.5162	0.066*
C10	0.2319 (6)	0.60912 (7)	0.4943 (4)	0.0603 (7)
C11	0.4782 (6)	0.65640 (8)	0.7057 (5)	0.0705 (8)
H11A	0.4619	0.6483	0.8252	0.085*
H11B	0.6199	0.6475	0.7076	0.085*
C12	0.5028 (6)	0.69233 (8)	0.7230 (4)	0.0680 (8)
H12A	0.3713	0.7013	0.7395	0.082*
H12B	0.6445	0.6979	0.8438	0.082*
C13	0.5117 (5)	0.70604 (7)	0.5299 (4)	0.0557 (7)
C14	0.2935 (5)	0.69553 (7)	0.3383 (4)	0.0535 (6)
H14	0.1604	0.7019	0.3644	0.064*
C15	0.2898 (7)	0.71750 (8)	0.1690 (5)	0.0689 (8)
H15A	0.1348	0.7185	0.0553	0.083*
H15B	0.3996	0.7105	0.1166	0.083*
C16	0.3625 (6)	0.74974 (8)	0.2781 (5)	0.0684 (8)
H16A	0.4656	0.7609	0.2329	0.082*
H16B	0.2268	0.7628	0.2509	0.082*
C17	0.4877 (5)	0.74133 (8)	0.5051 (5)	0.0588 (7)
C18	0.7419 (6)	0.69719 (10)	0.5206 (7)	0.0807 (10)
H18A	0.7420	0.7056	0.3963	0.121*
H18B	0.7564	0.6746	0.5210	0.121*
H18C	0.8709	0.7059	0.6385	0.121*
C19	0.4422 (6)	0.59183 (9)	0.4906 (6)	0.0735 (9)
H19A	0.4887	0.6022	0.3953	0.110*
H19B	0.4002	0.5703	0.4478	0.110*
H19C	0.5696	0.5921	0.6264	0.110*
N2	0.7478 (5)	0.79799 (6)	1.0431 (4)	0.0625 (6)
O2	0.7739 (5)	0.76556 (5)	1.0955 (4)	0.0754 (6)
H2	0.7177	0.7549	0.9897	0.113*
C21	0.3214 (7)	0.95799 (9)	1.0351 (6)	0.0862 (11)
H21A	0.1940	0.9461	1.0410	0.103*
H21B	0.3238	0.9535	0.9035	0.103*
C22	0.2755 (10)	0.99341 (11)	1.0460 (8)	0.1069 (15)
H22A	0.3635	1.0053	0.9879	0.128*
H22B	0.1110	0.9977	0.9626	0.128*
C23	0.3417 (8)	1.00439 (10)	1.2611 (8)	0.0950 (12)
H23	0.2982	1.0247	1.2807	0.114*
C24	0.4578 (8)	0.98696 (10)	1.4236 (8)	0.0869 (11)
H24	0.4968	0.9957	1.5533	0.104*
C25	0.5323 (7)	0.95347 (8)	1.4127 (5)	0.0704 (8)
H25	0.4050	0.9400	1.4093	0.085*
C26	0.7473 (8)	0.94298 (9)	1.5986 (5)	0.0800 (10)
H26A	0.7312	0.9480	1.7237	0.096*
H26B	0.8828	0.9541	1.6028	0.096*
C27	0.7814 (8)	0.90735 (8)	1.5877 (5)	0.0771 (10)
H27A	0.9252	0.9011	1.7039	0.093*
H27B	0.6536	0.8963	1.5993	0.093*
C28	0.7913 (5)	0.89752 (7)	1.3874 (4)	0.0556 (6)
H28	0.9355	0.9059	1.3881	0.067*
C29	0.5821 (5)	0.91081 (7)	1.1966 (4)	0.0559 (7)
H29	0.4424	0.9011	1.1973	0.067*
C30	0.5511 (6)	0.94693 (7)	1.2093 (5)	0.0603 (7)
C31	0.5894 (7)	0.89993 (8)	0.9952 (5)	0.0705 (8)
H31A	0.4498	0.9073	0.8787	0.085*
H31B	0.7230	0.9095	0.9855	0.085*
C32	0.6059 (6)	0.86397 (8)	0.9809 (4)	0.0665 (8)
H32A	0.4635	0.8543	0.9723	0.080*
H32B	0.6224	0.8585	0.8566	0.080*
C33	0.8128 (5)	0.85132 (7)	1.1681 (4)	0.0558 (7)
C34	0.7914 (5)	0.86164 (7)	1.3648 (4)	0.0546 (6)
H34	0.6363	0.8546	1.3457	0.066*
C35	0.9650 (7)	0.84048 (9)	1.5344 (5)	0.0706 (8)
H35A	0.9274	0.8392	1.6516	0.085*
H35B	1.1235	0.8482	1.5812	0.085*
C36	0.9343 (7)	0.80801 (8)	1.4264 (5)	0.0705 (8)
H36A	1.0837	0.7975	1.4678	0.085*
H36B	0.8319	0.7944	1.4591	0.085*
C37	0.8265 (5)	0.81600 (8)	1.1984 (4)	0.0583 (7)
C38	1.0450 (7)	0.86152 (10)	1.1668 (7)	0.0821 (11)
H38A	1.1731	0.8533	1.2873	0.123*
H38B	1.0537	0.8842	1.1673	0.123*
H38C	1.0529	0.8534	1.0450	0.123*
C39	0.7545 (7)	0.96533 (8)	1.2004 (6)	0.0762 (9)
H39A	0.8997	0.9559	1.2936	0.114*
H39B	0.7493	0.9869	1.2398	0.114*
H39C	0.7419	0.9647	1.0622	0.114*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0652 (15)	0.0652 (16)	0.0618 (14)	−0.0069 (12)	0.0280 (12)	−0.0147 (12)
O1	0.0887 (17)	0.0652 (14)	0.0729 (15)	−0.0087 (12)	0.0311 (13)	−0.0143 (11)
C1	0.096 (2)	0.081 (2)	0.072 (2)	−0.009 (2)	0.0441 (19)	−0.0028 (17)
C2	0.129 (4)	0.085 (3)	0.093 (3)	−0.018 (3)	0.058 (3)	0.004 (2)
C3	0.106 (3)	0.076 (3)	0.107 (3)	−0.020 (2)	0.046 (3)	−0.006 (2)
C4	0.084 (3)	0.081 (3)	0.085 (3)	−0.0165 (19)	0.026 (2)	−0.013 (2)
C5	0.0620 (18)	0.068 (2)	0.0656 (19)	−0.0043 (14)	0.0172 (15)	−0.0102 (15)
C6	0.091 (3)	0.074 (2)	0.0451 (15)	−0.0070 (18)	0.0035 (15)	−0.0109 (15)
C7	0.082 (2)	0.070 (2)	0.0407 (15)	−0.0057 (16)	0.0054 (14)	−0.0080 (14)
C8	0.0554 (15)	0.0636 (17)	0.0417 (13)	−0.0003 (12)	0.0166 (11)	−0.0082 (11)
C9	0.0526 (14)	0.0632 (16)	0.0471 (14)	0.0029 (12)	0.0201 (11)	−0.0068 (12)
C10	0.0626 (17)	0.0655 (18)	0.0520 (15)	0.0007 (14)	0.0241 (13)	−0.0054 (13)
C11	0.077 (2)	0.072 (2)	0.0459 (15)	−0.0012 (16)	0.0110 (14)	−0.0033 (14)
C12	0.0707 (18)	0.076 (2)	0.0420 (14)	−0.0019 (15)	0.0104 (13)	−0.0124 (13)
C13	0.0479 (14)	0.0663 (17)	0.0499 (15)	0.0001 (12)	0.0184 (11)	−0.0137 (13)
C14	0.0517 (14)	0.0646 (17)	0.0410 (13)	0.0007 (12)	0.0171 (11)	−0.0092 (11)
C15	0.080 (2)	0.074 (2)	0.0516 (16)	−0.0072 (16)	0.0276 (15)	−0.0088 (14)
C16	0.074 (2)	0.075 (2)	0.0541 (16)	−0.0096 (16)	0.0259 (15)	−0.0099 (14)
C17	0.0530 (15)	0.0674 (18)	0.0583 (16)	−0.0073 (13)	0.0263 (13)	−0.0140 (13)
C18	0.0522 (16)	0.095 (3)	0.094 (3)	−0.0005 (16)	0.0300 (16)	−0.022 (2)
C19	0.0689 (19)	0.070 (2)	0.079 (2)	0.0092 (16)	0.0297 (17)	−0.0021 (16)
N2	0.0638 (14)	0.0642 (16)	0.0630 (15)	−0.0063 (12)	0.0307 (12)	−0.0147 (12)
O2	0.0868 (16)	0.0646 (14)	0.0722 (15)	−0.0004 (11)	0.0319 (13)	−0.0151 (11)
C21	0.088 (3)	0.070 (2)	0.082 (2)	0.0029 (18)	0.019 (2)	−0.0028 (18)
C22	0.111 (3)	0.075 (3)	0.106 (3)	0.015 (2)	0.020 (3)	−0.003 (2)
C23	0.097 (3)	0.069 (2)	0.121 (4)	0.009 (2)	0.049 (3)	−0.007 (2)
C24	0.096 (3)	0.076 (2)	0.104 (3)	0.000 (2)	0.057 (3)	−0.017 (2)
C25	0.083 (2)	0.0665 (19)	0.076 (2)	−0.0034 (16)	0.0472 (18)	−0.0099 (16)
C26	0.119 (3)	0.072 (2)	0.0547 (17)	0.006 (2)	0.0424 (19)	−0.0125 (15)
C27	0.115 (3)	0.069 (2)	0.0494 (16)	0.0047 (19)	0.0374 (17)	−0.0072 (15)
C28	0.0617 (16)	0.0613 (17)	0.0464 (14)	−0.0072 (12)	0.0260 (12)	−0.0097 (12)
C29	0.0579 (15)	0.0613 (17)	0.0510 (14)	−0.0091 (12)	0.0259 (12)	−0.0062 (12)
C30	0.0645 (17)	0.0590 (17)	0.0595 (16)	−0.0064 (13)	0.0288 (14)	−0.0054 (13)
C31	0.095 (2)	0.069 (2)	0.0465 (15)	−0.0045 (17)	0.0301 (16)	−0.0059 (14)
C32	0.082 (2)	0.072 (2)	0.0455 (14)	−0.0113 (16)	0.0278 (14)	−0.0128 (13)
C33	0.0574 (16)	0.0647 (17)	0.0523 (15)	−0.0128 (12)	0.0304 (13)	−0.0151 (13)
C34	0.0582 (15)	0.0634 (17)	0.0442 (13)	−0.0047 (13)	0.0240 (12)	−0.0084 (12)
C35	0.077 (2)	0.074 (2)	0.0484 (16)	0.0025 (16)	0.0149 (14)	−0.0092 (14)
C36	0.077 (2)	0.072 (2)	0.0602 (18)	0.0041 (16)	0.0271 (16)	−0.0077 (15)
C37	0.0507 (15)	0.0706 (19)	0.0581 (16)	−0.0044 (13)	0.0277 (13)	−0.0131 (14)
C38	0.079 (2)	0.091 (3)	0.100 (3)	−0.0212 (19)	0.061 (2)	−0.023 (2)
C39	0.095 (2)	0.0624 (19)	0.087 (2)	−0.0158 (17)	0.055 (2)	−0.0096 (16)

Geometric parameters (Å, º)

N1—C17	1.268 (4)	N2—C37	1.261 (4)
N1—O1	1.415 (4)	N2—O2	1.413 (3)
O1—H1	0.8200	O2—H2	0.8200
C1—C2	1.522 (6)	C21—C30	1.527 (5)
C1—C10	1.541 (5)	C21—C22	1.535 (5)
C1—H1A	0.9700	C21—H21A	0.9700
C1—H1B	0.9700	C21—H21B	0.9700
C2—C3	1.481 (7)	C22—C23	1.488 (7)
C2—H2A	0.9700	C22—H22A	0.9700
C2—H2B	0.9700	C22—H22B	0.9700
C3—C4	1.312 (6)	C23—C24	1.305 (6)
C3—H3	0.9300	C23—H23	0.9300
C4—C5	1.493 (5)	C24—C25	1.506 (5)
C4—H4	0.9300	C24—H24	0.9300
C5—C6	1.513 (5)	C25—C26	1.504 (6)
C5—C10	1.544 (4)	C25—C30	1.541 (4)
C5—H5	0.9800	C25—H25	0.9800
C6—C7	1.517 (5)	C26—C27	1.530 (5)
C6—H6A	0.9700	C26—H26A	0.9700
C6—H6B	0.9700	C26—H26B	0.9700
C7—C8	1.530 (4)	C27—C28	1.524 (4)
C7—H7A	0.9700	C27—H27A	0.9700
C7—H7B	0.9700	C27—H27B	0.9700
C8—C14	1.523 (4)	C28—C34	1.527 (4)
C8—C9	1.549 (4)	C28—C29	1.543 (4)
C8—H8	0.9800	C28—H28	0.9800
C9—C11	1.536 (4)	C29—C31	1.537 (4)
C9—C10	1.547 (4)	C29—C30	1.548 (4)
C9—H9	0.9800	C29—H29	0.9800
C10—C19	1.533 (4)	C30—C39	1.533 (4)
C11—C12	1.528 (5)	C31—C32	1.531 (5)
C11—H11A	0.9700	C31—H31A	0.9700
C11—H11B	0.9700	C31—H31B	0.9700
C12—C13	1.525 (4)	C32—C33	1.513 (5)
C12—H12A	0.9700	C32—H32A	0.9700
C12—H12B	0.9700	C32—H32B	0.9700
C13—C17	1.503 (4)	C33—C37	1.507 (4)
C13—C14	1.536 (4)	C33—C34	1.538 (4)
C13—C18	1.539 (4)	C33—C38	1.541 (4)
C14—C15	1.522 (4)	C34—C35	1.529 (5)
C14—H14	0.9800	C34—H34	0.9800
C15—C16	1.541 (4)	C35—C36	1.547 (5)
C15—H15A	0.9700	C35—H35A	0.9700
C15—H15B	0.9700	C35—H35B	0.9700
C16—C17	1.514 (5)	C36—C37	1.514 (4)
C16—H16A	0.9700	C36—H36A	0.9700
C16—H16B	0.9700	C36—H36B	0.9700
C18—H18A	0.9600	C38—H38A	0.9600
C18—H18B	0.9600	C38—H38B	0.9600
C18—H18C	0.9600	C38—H38C	0.9600
C19—H19A	0.9600	C39—H39A	0.9600
C19—H19B	0.9600	C39—H39B	0.9600
C19—H19C	0.9600	C39—H39C	0.9600
C17—N1—O1	113.2 (3)	C37—N2—O2	113.3 (3)
N1—O1—H1	109.5	N2—O2—H2	109.5
C2—C1—C10	113.7 (3)	C30—C21—C22	113.1 (3)
C2—C1—H1A	108.8	C30—C21—H21A	109.0
C10—C1—H1A	108.8	C22—C21—H21A	109.0
C2—C1—H1B	108.8	C30—C21—H21B	109.0
C10—C1—H1B	108.8	C22—C21—H21B	109.0
H1A—C1—H1B	107.7	H21A—C21—H21B	107.8
C3—C2—C1	112.5 (4)	C23—C22—C21	112.5 (4)
C3—C2—H2A	109.1	C23—C22—H22A	109.1
C1—C2—H2A	109.1	C21—C22—H22A	109.1
C3—C2—H2B	109.1	C23—C22—H22B	109.1
C1—C2—H2B	109.1	C21—C22—H22B	109.1
H2A—C2—H2B	107.8	H22A—C22—H22B	107.8
C4—C3—C2	123.3 (4)	C24—C23—C22	123.2 (4)
C4—C3—H3	118.4	C24—C23—H23	118.4
C2—C3—H3	118.4	C22—C23—H23	118.4
C3—C4—C5	123.9 (4)	C23—C24—C25	123.6 (4)
C3—C4—H4	118.0	C23—C24—H24	118.2
C5—C4—H4	118.0	C25—C24—H24	118.2
C4—C5—C6	114.9 (3)	C26—C25—C24	114.6 (3)
C4—C5—C10	111.7 (3)	C26—C25—C30	112.0 (3)
C6—C5—C10	111.8 (3)	C24—C25—C30	111.9 (3)
C4—C5—H5	105.9	C26—C25—H25	105.9
C6—C5—H5	105.9	C24—C25—H25	105.9
C10—C5—H5	105.9	C30—C25—H25	105.9
C5—C6—C7	110.7 (3)	C25—C26—C27	109.8 (3)
C5—C6—H6A	109.5	C25—C26—H26A	109.7
C7—C6—H6A	109.5	C27—C26—H26A	109.7
C5—C6—H6B	109.5	C25—C26—H26B	109.7
C7—C6—H6B	109.5	C27—C26—H26B	109.7
H6A—C6—H6B	108.1	H26A—C26—H26B	108.2
C6—C7—C8	112.5 (3)	C28—C27—C26	112.4 (3)
C6—C7—H7A	109.1	C28—C27—H27A	109.1
C8—C7—H7A	109.1	C26—C27—H27A	109.1
C6—C7—H7B	109.1	C28—C27—H27B	109.1
C8—C7—H7B	109.1	C26—C27—H27B	109.1
H7A—C7—H7B	107.8	H27A—C27—H27B	107.9
C14—C8—C7	112.1 (2)	C27—C28—C34	112.0 (2)
C14—C8—C9	108.2 (2)	C27—C28—C29	111.5 (3)
C7—C8—C9	111.3 (3)	C34—C28—C29	107.9 (2)
C14—C8—H8	108.4	C27—C28—H28	108.5
C7—C8—H8	108.4	C34—C28—H28	108.5
C9—C8—H8	108.4	C29—C28—H28	108.5
C11—C9—C10	114.1 (2)	C31—C29—C28	111.1 (3)
C11—C9—C8	111.3 (3)	C31—C29—C30	114.0 (2)
C10—C9—C8	113.0 (2)	C28—C29—C30	112.9 (2)
C11—C9—H9	105.9	C31—C29—H29	106.0
C10—C9—H9	105.9	C28—C29—H29	106.0
C8—C9—H9	105.9	C30—C29—H29	106.0
C19—C10—C1	108.9 (3)	C21—C30—C39	109.5 (3)
C19—C10—C5	111.7 (3)	C21—C30—C25	106.4 (3)
C1—C10—C5	105.9 (3)	C39—C30—C25	111.2 (3)
C19—C10—C9	111.5 (3)	C21—C30—C29	110.8 (3)
C1—C10—C9	111.4 (2)	C39—C30—C29	111.6 (3)
C5—C10—C9	107.3 (2)	C25—C30—C29	107.3 (2)
C12—C11—C9	113.3 (2)	C32—C31—C29	113.0 (3)
C12—C11—H11A	108.9	C32—C31—H31A	109.0
C9—C11—H11A	108.9	C29—C31—H31A	109.0
C12—C11—H11B	108.9	C32—C31—H31B	109.0
C9—C11—H11B	108.9	C29—C31—H31B	109.0
H11A—C11—H11B	107.7	H31A—C31—H31B	107.8
C13—C12—C11	110.3 (2)	C33—C32—C31	110.5 (3)
C13—C12—H12A	109.6	C33—C32—H32A	109.5
C11—C12—H12A	109.6	C31—C32—H32A	109.5
C13—C12—H12B	109.6	C33—C32—H32B	109.5
C11—C12—H12B	109.6	C31—C32—H32B	109.5
H12A—C12—H12B	108.1	H32A—C32—H32B	108.1
C17—C13—C12	116.3 (2)	C37—C33—C32	116.9 (2)
C17—C13—C14	100.1 (2)	C37—C33—C34	99.9 (2)
C12—C13—C14	109.2 (2)	C32—C33—C34	109.1 (2)
C17—C13—C18	106.6 (3)	C37—C33—C38	106.4 (3)
C12—C13—C18	110.9 (3)	C32—C33—C38	111.2 (3)
C14—C13—C18	113.4 (2)	C34—C33—C38	113.0 (2)
C15—C14—C8	122.5 (2)	C28—C34—C35	122.1 (2)
C15—C14—C13	103.5 (2)	C28—C34—C33	112.6 (2)
C8—C14—C13	112.9 (2)	C35—C34—C33	104.2 (2)
C15—C14—H14	105.5	C28—C34—H34	105.6
C8—C14—H14	105.5	C35—C34—H34	105.6
C13—C14—H14	105.5	C33—C34—H34	105.6
C14—C15—C16	103.7 (2)	C34—C35—C36	103.3 (2)
C14—C15—H15A	111.0	C34—C35—H35A	111.1
C16—C15—H15A	111.0	C36—C35—H35A	111.1
C14—C15—H15B	111.0	C34—C35—H35B	111.1
C16—C15—H15B	111.0	C36—C35—H35B	111.1
H15A—C15—H15B	109.0	H35A—C35—H35B	109.1
C17—C16—C15	103.9 (3)	C37—C36—C35	104.1 (3)
C17—C16—H16A	111.0	C37—C36—H36A	110.9
C15—C16—H16A	111.0	C35—C36—H36A	110.9
C17—C16—H16B	111.0	C37—C36—H36B	110.9
C15—C16—H16B	111.0	C35—C36—H36B	110.9
H16A—C16—H16B	109.0	H36A—C36—H36B	109.0
N1—C17—C13	120.5 (3)	N2—C37—C33	119.7 (3)
N1—C17—C16	129.6 (3)	N2—C37—C36	129.9 (3)
C13—C17—C16	109.9 (2)	C33—C37—C36	110.4 (2)
C13—C18—H18A	109.5	C33—C38—H38A	109.5
C13—C18—H18B	109.5	C33—C38—H38B	109.5
H18A—C18—H18B	109.5	H38A—C38—H38B	109.5
C13—C18—H18C	109.5	C33—C38—H38C	109.5
H18A—C18—H18C	109.5	H38A—C38—H38C	109.5
H18B—C18—H18C	109.5	H38B—C38—H38C	109.5
C10—C19—H19A	109.5	C30—C39—H39A	109.5
C10—C19—H19B	109.5	C30—C39—H39B	109.5
H19A—C19—H19B	109.5	H39A—C39—H39B	109.5
C10—C19—H19C	109.5	C30—C39—H39C	109.5
H19A—C19—H19C	109.5	H39A—C39—H39C	109.5
H19B—C19—H19C	109.5	H39B—C39—H39C	109.5
C10—C1—C2—C3	−39.3 (5)	C21—C22—C23—C24	9.7 (7)
C1—C2—C3—C4	8.2 (7)	C22—C23—C24—C25	−1.9 (8)
C2—C3—C4—C5	−1.1 (8)	C23—C24—C25—C26	152.8 (4)
C3—C4—C5—C6	153.1 (4)	C23—C24—C25—C30	23.9 (6)
C3—C4—C5—C10	24.4 (6)	C24—C25—C26—C27	170.2 (3)
C4—C5—C6—C7	171.1 (3)	C30—C25—C26—C27	−61.0 (4)
C10—C5—C6—C7	−60.3 (4)	C25—C26—C27—C28	55.5 (4)
C5—C6—C7—C8	54.8 (4)	C26—C27—C28—C34	−172.1 (3)
C6—C7—C8—C14	−172.1 (3)	C26—C27—C28—C29	−51.1 (4)
C6—C7—C8—C9	−50.7 (4)	C27—C28—C29—C31	−178.2 (3)
C14—C8—C9—C11	−54.1 (3)	C34—C28—C29—C31	−54.9 (3)
C7—C8—C9—C11	−177.7 (3)	C27—C28—C29—C30	52.2 (3)
C14—C8—C9—C10	176.0 (2)	C34—C28—C29—C30	175.5 (2)
C7—C8—C9—C10	52.3 (3)	C22—C21—C30—C39	−59.3 (5)
C2—C1—C10—C19	−59.8 (4)	C22—C21—C30—C25	60.9 (5)
C2—C1—C10—C5	60.5 (4)	C22—C21—C30—C29	177.2 (4)
C2—C1—C10—C9	176.8 (3)	C26—C25—C30—C21	178.9 (3)
C4—C5—C10—C19	67.4 (4)	C24—C25—C30—C21	−50.9 (4)
C6—C5—C10—C19	−62.8 (4)	C26—C25—C30—C39	−62.0 (4)
C4—C5—C10—C1	−51.0 (4)	C24—C25—C30—C39	68.2 (4)
C6—C5—C10—C1	178.7 (3)	C26—C25—C30—C29	60.3 (4)
C4—C5—C10—C9	−170.1 (3)	C24—C25—C30—C29	−169.5 (3)
C6—C5—C10—C9	59.7 (3)	C31—C29—C30—C21	60.9 (4)
C11—C9—C10—C19	−61.6 (3)	C28—C29—C30—C21	−171.0 (3)
C8—C9—C10—C19	66.9 (3)	C31—C29—C30—C39	−61.4 (4)
C11—C9—C10—C1	60.3 (4)	C28—C29—C30—C39	66.7 (3)
C8—C9—C10—C1	−171.2 (3)	C31—C29—C30—C25	176.6 (3)
C11—C9—C10—C5	175.8 (3)	C28—C29—C30—C25	−55.3 (3)
C8—C9—C10—C5	−55.7 (3)	C28—C29—C31—C32	54.3 (4)
C10—C9—C11—C12	−176.6 (3)	C30—C29—C31—C32	−176.7 (3)
C8—C9—C11—C12	54.0 (4)	C29—C31—C32—C33	−54.7 (4)
C9—C11—C12—C13	−54.7 (4)	C31—C32—C33—C37	168.4 (2)
C11—C12—C13—C17	168.3 (3)	C31—C32—C33—C34	56.1 (3)
C11—C12—C13—C14	55.9 (3)	C31—C32—C33—C38	−69.1 (3)
C11—C12—C13—C18	−69.7 (3)	C27—C28—C34—C35	−52.4 (4)
C7—C8—C14—C15	−53.3 (4)	C29—C28—C34—C35	−175.4 (3)
C9—C8—C14—C15	−176.4 (3)	C27—C28—C34—C33	−177.4 (3)
C7—C8—C14—C13	−178.1 (3)	C29—C28—C34—C33	59.6 (3)
C9—C8—C14—C13	58.7 (3)	C37—C33—C34—C28	175.9 (2)
C17—C13—C14—C15	42.3 (3)	C32—C33—C34—C28	−61.0 (3)
C12—C13—C14—C15	164.9 (3)	C38—C33—C34—C28	63.2 (4)
C18—C13—C14—C15	−70.9 (4)	C37—C33—C34—C35	41.6 (3)
C17—C13—C14—C8	176.9 (2)	C32—C33—C34—C35	164.7 (3)
C12—C13—C14—C8	−60.5 (3)	C38—C33—C34—C35	−71.1 (3)
C18—C13—C14—C8	63.7 (4)	C28—C34—C35—C36	−168.5 (3)
C8—C14—C15—C16	−169.0 (3)	C33—C34—C35—C36	−39.7 (3)
C13—C14—C15—C16	−40.1 (3)	C34—C35—C36—C37	21.1 (4)
C14—C15—C16—C17	21.1 (3)	O2—N2—C37—C33	179.7 (2)
O1—N1—C17—C13	−179.8 (3)	O2—N2—C37—C36	−2.3 (5)
O1—N1—C17—C16	−1.9 (5)	C32—C33—C37—N2	32.3 (4)
C12—C13—C17—N1	31.2 (4)	C34—C33—C37—N2	149.7 (3)
C14—C13—C17—N1	148.7 (3)	C38—C33—C37—N2	−92.6 (3)
C18—C13—C17—N1	−93.0 (3)	C32—C33—C37—C36	−146.1 (3)
C12—C13—C17—C16	−147.0 (3)	C34—C33—C37—C36	−28.7 (3)
C14—C13—C17—C16	−29.6 (3)	C38—C33—C37—C36	89.0 (3)
C18—C13—C17—C16	88.7 (3)	C35—C36—C37—N2	−173.1 (3)
C15—C16—C17—N1	−172.4 (3)	C35—C36—C37—C33	5.1 (4)
C15—C16—C17—C13	5.7 (3)	C18—C13—C10—C19	2.1 (3)
C30—C21—C22—C23	−40.6 (6)	C38—C33—C30—C39	2.7 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N2	0.82	2.11	2.805 (4)	142
O2—H2···N1	0.82	2.13	2.815 (3)	142
C16—H16A···O2^i	0.97	2.55	3.458 (4)	155
C16—H16B···O2^ii	0.97	2.60	3.449 (5)	147
C36—H36A···O1^iii	0.97	2.55	3.465 (5)	158

Symmetry codes: (i) x, y, z−1; (ii) x−1, y, z−1; (iii) x+1, y, z+1.