16-(4-Cyanobenzylidene)-3[beta]-pyrrolidinoandrost-5-en-17[beta]-ol monohydrate

In the title compound, C₃₁H₄₀N₂O·H₂O, the outer two six-membered rings are in chair conformations, while the central ring is in an 8[beta],9[alpha]-half-chair conformation. The five-membered ring adopts a 13[beta]-envelope conformation and the cyano­benzyl­idene moiety has an E configuration with respect to the hydroxyl group at position 17. The steroid nuclei are linked by intermolecular O-H...O and O-H...N hydrogen bonds to form a molecular network. The molecular packing has an interesting feature, with the steroids aligned parallel to the b axis, forming a closed loop through hydrogen bonds linked via water mol­ecules.

S1. Comment

The X-ray investigation of the title compound, (I), was undertaken as part of our study of the structure and conformation of new synthetic steroid derivatives. We are particularly interested in the conformational flexibilities of steroids due to various possible substitutions at the C3, C16 and C17 positions, as it is well known that steroid receptors are able to modify the mode of binding at ring D to accommodate several different types of C17 substitution (Duax & Norton, 1975). The absolute configuration of (I) was not determined from the X-ray data, but is based on the known chirality of the starting material used in the synthesis of (I), namely, 16-(4-cyanobenzylidene)androst-4-ene-3,17-dione. \sch

The C5—C6 distance of 1.332 (4) Å confirms the localization of a double bond at this position (Kálmán et al., 1992; Vasuki et al., 2001). The puckering parameters [ring A: Q = 0.542 (3) Å, θ = 2.7 (3)° and Φ = 42.8 (7)°; ring C: Q = 0.562 (3) Å, θ = 8.6 (3)° and Φ = 235.0 (2)°; Cremer & Pople, 1975] show that rings A and C adopt chair conformations. The presence of the pyrrolidine group bonded to C3 does not disturb the usual chair conformation of ring A of the steroidal nucleus. Due to the C5—C6 double bond, the environment of atom C5 is planar, and hence ring B adopts the half-chair conformation generally found in steroids with a C5—C6 double bond (Caira et al., 1995; Andrade et al., 2001), with puckering parameters Q = 0.490 (3) Å, θ = 49.4 (4)° and Φ = 202.5 (5)°.

The conformation of ring D can be expressed by two parameters, a pseudo rotation angle, Δ, and a maximum torsion angle, ϕ_m (Altona et al., 1968). In compound (I), ring D exhibits a 13β-envelope conformation, with Δ = 28.5° and ϕ_m = 48.2 (2)°.

Atoms C8 and C9 are displaced to opposite sides by 0.2631 (3) and 0.2155 (3) Å, respectively, from the mean C10/C5/C6/C7 plane. The C17—C16—C20—C21 torsion angle of -177.7 (3)° indicates that the cyanobenzylidene moiety has an E configuration with respect to the hydroxyl group at position 17. The C15—C16—C20 exocyclic angle of 131.0 (3)° is significantly larger than the normal value, and this may be due to the steric repulsion between atoms H15A and H26 [2.293 Å] and H15B and H26 [2.354 Å].

The pseudotorsion angle of C19—C10···C13—C18 is 12.41 (3)°. The 4-cyanobenzylidene group is oriented at an angle of 11.14 (10)° with respect to the central steroid nucleus. The equatorially substituted pyrrolidine group at C3 is oriented at an angle of 22.64 (12)° with respect to the central steroid nucleus. The geometry of the rings is trans at ring junctions B/C and C/D. In (I), the valency angles C8—C14—C15 [119.5 (2)°] and C14—C13—C17 [98.8 (2)°] are close to the expected values of 121.2° and 101.4°, respectively (Duax & Norton, 1975).

The 17β-OH is equatorially attached at C17 and the pyrrolidine is equatorially substituted at C3. The structure of (I) is stabilized by a network of O—H···O and O—H···N intermolecular hydrogen bonds (Table 1). The hydroxyl O atoms take part in the intermolecular hydrogen bonds as donors, with the O atoms of the water molecules as acceptors. The water molecule links three different steroid molecules, acting as a hydrogen-bond acceptor from O17 of one steroid molecule and as a donor to the N atoms of the pyrrolidine and 4-cyanobenzylidene of two other steroid molecules. In Fig. 2, we see that the steroid molecules are aligned parallel to the b axis, forming a closed loop through hydrogen bonds linked via water molecules.

S2. Experimental

Freshly distilled pyrrolidine was added to a refluxing solution of 16-(4-cyanobenzylidene)androst-4-ene-3,17-dione (0.5 g, 1.25 mmol) in methanol (50 ml). After refluxing for 15 min, the precipitate obtained was cooled in ice, filtered and washed with methanol to obtain 16-(4-cyanobenzylidene)-3-pyrrolidinoandrosta-3,5-dien-17-one (0.4 g). This was immediately suspended in methanol (50 ml) and reduced with sodium borohydride (1.0 g), while stirring at room temperature. The stirring was continued for 4 h, excess methanol was removed under reduced pressure and ice-cold water was added. The precipitate obtained was filtered, washed with water, dried and crystallized from acetone to obtain (I) (0.23 g, 56.99%; m.p. 501–507 K). Spectroscopic analysis: UV_max (MeOH): 282.2 nm (log ε = 4.47); IR_νmax (KBr, cm^-1): 3350, 2980, 2200, 1595; ¹H NMR (CDCl₃ + DMSO, δ, p.p.m.): 0.69 (s, 3H, 18-CH₃), 1.02 (s, 3H, 19-CH₃), 2.61 (s, 4H, N-methylene of pyrrolidine function), 4.02 (m, 1H, 3α-H), 5.36 (s, 2H, 6-CH), 6.55 [s, 1H, vinyl H of 16-(4-cyanobenzylidene)], 7.47 (d, 2H, J_o = 8.3 Hz, 2-CH and 6-CH aromatic H), 7.67 (d, 2H, J_o = 8.3 Hz, 3-CH and 5-CH aromatic H); MS: m/z (mass/relative intensity): 456 [M⁺].

S3. Refinement

All H atoms were fixed with geometrical considerations (C—H = 0.93–0.98 Å and O—H = 0.82 Å Are these the correct constraints?), except water H atoms, for which the overall displacement parameters were refined.

Computing details

Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: MolEN (Fair, 1990); program(s) used to solve structure: DIRDIF99 (Beurskens et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: WinGX (Farrugia, 1999); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. The molecular structure of (I) showing 50% probability displacement ellipsoids and the atom-numbering scheme. H atoms have been omitted for clarity.
	Fig. 2. A stereoview of the molecular packing of (I) viewed down the b axis.

16-(4-Cyanobenzylidene)-3β-pyrrolidinoandrost-5-en-17β-ol monohydrate

Crystal data

C31H40N2O·H2O	Dx = 1.168 Mg m^−3
Mr = 474.67	Cu Kα radiation, λ = 1.54180 Å
Orthorhombic, P212121	Cell parameters from 25 reflections
a = 7.2171 (6) Å	θ = 20–30°
b = 18.541 (3) Å	µ = 0.56 mm^−1
c = 20.176 (6) Å	T = 293 K
V = 2699.8 (9) Å^3	Plate, colourless
Z = 4	0.30 × 0.25 × 0.10 mm
F(000) = 1032

Data collection

Enraf-Nonius CAD-4 diffractometer	2580 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.016
Graphite monochromator	θmax = 68.0°, θmin = 3.2°
ω/2θ scans	h = −8→2
Absorption correction: ψ scan (North et al., 1968)	k = −22→9
Tmin = 0.850, Tmax = 0.946	l = −24→10
2916 measured reflections	2 standard reflections every 100 reflections
2898 independent reflections	intensity decay: none

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.043	w = 1/[σ^2(Fo^2) + (0.0626P)^2 + 0.6312P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.123	(Δ/σ)max < 0.001
S = 1.09	Δρmax = 0.19 e Å^−3
2898 reflections	Δρmin = −0.19 e Å^−3
318 parameters	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0021 (3)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 83 Friedel pairs Query
Secondary atom site location: difference Fourier map	Absolute structure parameter: −1.4 (5)

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
C1	−0.4606 (4)	−0.18329 (15)	−0.65575 (18)	0.0628 (8)
H1A	−0.5750	−0.1940	−0.6790	0.075*
H1B	−0.4924	−0.1707	−0.6105	0.075*
C2	−0.3693 (4)	−0.11851 (15)	−0.68839 (17)	0.0634 (8)
H2A	−0.4521	−0.0774	−0.6856	0.076*
H2B	−0.3486	−0.1289	−0.7349	0.076*
C3	−0.1842 (5)	−0.09927 (15)	−0.65563 (15)	0.0582 (7)
H3	−0.2083	−0.0840	−0.6099	0.070*
C4	−0.0594 (4)	−0.16564 (16)	−0.65401 (18)	0.0665 (8)
H4A	−0.0203	−0.1771	−0.6988	0.080*
H4B	0.0505	−0.1549	−0.6282	0.080*
C5	−0.1561 (4)	−0.23056 (15)	−0.62438 (13)	0.0497 (6)
C6	−0.0748 (4)	−0.26771 (15)	−0.57590 (16)	0.0613 (8)
H6	0.0389	−0.2513	−0.5604	0.074*
C7	−0.1540 (4)	−0.33385 (14)	−0.54483 (14)	0.0544 (7)
H7A	−0.2089	−0.3213	−0.5025	0.065*
H7B	−0.0552	−0.3682	−0.5366	0.065*
C8	−0.3006 (4)	−0.36886 (13)	−0.58871 (13)	0.0458 (6)
H8	−0.2395	−0.3905	−0.6273	0.055*
C9	−0.4363 (4)	−0.31064 (14)	−0.61280 (13)	0.0482 (6)
H9	−0.4809	−0.2863	−0.5728	0.058*
C10	−0.3398 (4)	−0.25153 (14)	−0.65485 (13)	0.0477 (6)
C11	−0.6106 (4)	−0.34276 (17)	−0.64664 (17)	0.0643 (8)
H11A	−0.7000	−0.3045	−0.6539	0.077*
H11B	−0.5759	−0.3620	−0.6896	0.077*
C12	−0.7016 (4)	−0.40240 (17)	−0.60600 (18)	0.0655 (8)
H12A	−0.7496	−0.3823	−0.5651	0.079*
H12B	−0.8048	−0.4224	−0.6307	0.079*
C13	−0.5640 (4)	−0.46195 (15)	−0.58998 (13)	0.0527 (6)
C14	−0.4037 (4)	−0.42741 (14)	−0.55113 (12)	0.0471 (6)
H14	−0.4604	−0.4036	−0.5128	0.057*
C15	−0.2960 (4)	−0.49195 (14)	−0.52334 (14)	0.0522 (7)
H15A	−0.2033	−0.5086	−0.5546	0.063*
H15B	−0.2357	−0.4797	−0.4819	0.063*
C16	−0.4454 (4)	−0.54836 (15)	−0.51294 (13)	0.0523 (7)
C17	−0.6276 (4)	−0.51696 (17)	−0.53783 (15)	0.0592 (7)
H17	−0.6832	−0.4899	−0.5011	0.071*
O17	−0.7552 (4)	−0.57058 (14)	−0.55695 (14)	0.0925 (9)
H17A	−0.8097	−0.5576	−0.5906	0.139*
C18	−0.4999 (5)	−0.50178 (17)	−0.65225 (14)	0.0676 (9)
H18A	−0.6052	−0.5225	−0.6742	0.101*
H18B	−0.4149	−0.5393	−0.6401	0.101*
H18C	−0.4394	−0.4685	−0.6816	0.101*
C19	−0.3067 (5)	−0.27759 (17)	−0.72614 (14)	0.0668 (9)
H19A	−0.4228	−0.2909	−0.7459	0.100*
H19B	−0.2255	−0.3186	−0.7256	0.100*
H19C	−0.2510	−0.2395	−0.7515	0.100*
C20	−0.4363 (5)	−0.61512 (16)	−0.48837 (13)	0.0569 (7)
H20	−0.5471	−0.6407	−0.4894	0.068*
C21	−0.2794 (4)	−0.65442 (14)	−0.46009 (13)	0.0528 (7)
C22	−0.3158 (5)	−0.72049 (15)	−0.42936 (14)	0.0598 (8)
H22	−0.4360	−0.7386	−0.4296	0.072*
C23	−0.1783 (5)	−0.75925 (16)	−0.39890 (16)	0.0634 (8)
H23	−0.2067	−0.8024	−0.3778	0.076*
C24	0.0020 (5)	−0.73452 (16)	−0.39943 (15)	0.0611 (8)
C241	0.1473 (6)	−0.77506 (19)	−0.36784 (18)	0.0750 (10)
N241	0.2620 (5)	−0.80736 (19)	−0.3434 (2)	0.1058 (12)
C25	0.0428 (5)	−0.66972 (17)	−0.43081 (16)	0.0676 (9)
H25	0.1639	−0.6525	−0.4313	0.081*
C26	−0.0958 (4)	−0.63103 (16)	−0.46109 (17)	0.0654 (8)
H26	−0.0665	−0.5882	−0.4828	0.078*
N31	−0.0956 (4)	−0.03955 (12)	−0.69112 (11)	0.0545 (6)
C32	0.0939 (5)	−0.02205 (17)	−0.66792 (18)	0.0701 (9)
H32A	0.1827	−0.0574	−0.6837	0.084*
H32B	0.0991	−0.0203	−0.6199	0.084*
C33	0.1315 (6)	0.05102 (18)	−0.69748 (19)	0.0772 (10)
H33A	0.2127	0.0789	−0.6690	0.093*
H33B	0.1888	0.0464	−0.7408	0.093*
C34	−0.0552 (6)	0.08622 (18)	−0.7030 (2)	0.0827 (11)
H34A	−0.0768	0.1027	−0.7480	0.099*
H34B	−0.0634	0.1273	−0.6733	0.099*
C35	−0.1954 (5)	0.02902 (15)	−0.68384 (18)	0.0682 (9)
H35A	−0.2365	0.0357	−0.6385	0.082*
H35B	−0.3022	0.0306	−0.7129	0.082*
O1W	0.0352 (4)	−0.57104 (17)	−0.67018 (12)	0.1064 (10)
H1W	−0.0346	−0.6051	−0.6671	0.085*
H2W	0.0372	−0.5610	−0.7175	0.050*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0479 (16)	0.0547 (16)	0.086 (2)	0.0035 (14)	−0.0014 (16)	0.0110 (16)
C2	0.0559 (17)	0.0501 (15)	0.084 (2)	0.0012 (14)	−0.0042 (17)	0.0120 (15)
C3	0.0675 (18)	0.0512 (15)	0.0559 (15)	−0.0091 (15)	−0.0007 (15)	0.0048 (13)
C4	0.0570 (18)	0.0569 (17)	0.086 (2)	−0.0087 (16)	−0.0111 (18)	0.0163 (16)
C5	0.0468 (14)	0.0495 (14)	0.0528 (14)	0.0007 (13)	0.0010 (13)	0.0011 (12)
C6	0.0504 (15)	0.0558 (15)	0.0778 (19)	−0.0105 (15)	−0.0162 (15)	0.0103 (15)
C7	0.0502 (15)	0.0527 (14)	0.0602 (16)	−0.0014 (13)	−0.0078 (14)	0.0064 (13)
C8	0.0441 (13)	0.0466 (13)	0.0467 (13)	0.0023 (12)	0.0006 (12)	0.0017 (11)
C9	0.0429 (13)	0.0518 (14)	0.0498 (14)	0.0019 (12)	−0.0016 (12)	0.0006 (12)
C10	0.0474 (14)	0.0464 (13)	0.0493 (13)	0.0020 (12)	−0.0009 (12)	0.0024 (11)
C11	0.0473 (16)	0.0638 (17)	0.082 (2)	−0.0076 (15)	−0.0159 (15)	0.0191 (16)
C12	0.0458 (16)	0.0712 (19)	0.080 (2)	−0.0097 (15)	−0.0128 (16)	0.0149 (17)
C13	0.0519 (15)	0.0563 (15)	0.0500 (14)	−0.0069 (14)	−0.0034 (13)	0.0113 (12)
C14	0.0463 (14)	0.0507 (14)	0.0443 (13)	−0.0018 (12)	0.0022 (12)	0.0028 (11)
C15	0.0503 (16)	0.0543 (15)	0.0519 (14)	−0.0008 (13)	0.0019 (13)	0.0078 (12)
C16	0.0549 (16)	0.0573 (15)	0.0445 (13)	−0.0045 (14)	0.0032 (13)	0.0047 (12)
C17	0.0517 (16)	0.0663 (17)	0.0597 (16)	−0.0104 (14)	0.0011 (14)	0.0135 (15)
O17	0.0824 (17)	0.0945 (17)	0.1007 (19)	−0.0428 (15)	−0.0277 (15)	0.0444 (15)
C18	0.085 (2)	0.0681 (19)	0.0492 (15)	−0.0183 (18)	−0.0041 (17)	0.0040 (14)
C19	0.084 (2)	0.0638 (17)	0.0528 (15)	−0.0094 (18)	0.0033 (17)	−0.0033 (14)
C20	0.0590 (17)	0.0598 (16)	0.0517 (14)	−0.0082 (15)	0.0025 (14)	0.0039 (13)
C21	0.0680 (18)	0.0485 (14)	0.0421 (13)	−0.0022 (14)	0.0054 (13)	0.0033 (12)
C22	0.073 (2)	0.0488 (15)	0.0581 (16)	−0.0101 (16)	0.0020 (16)	0.0020 (13)
C23	0.083 (2)	0.0481 (15)	0.0588 (17)	0.0005 (16)	0.0033 (17)	0.0078 (13)
C24	0.072 (2)	0.0526 (16)	0.0585 (16)	0.0085 (16)	0.0051 (16)	0.0011 (14)
C241	0.082 (2)	0.0639 (19)	0.079 (2)	0.013 (2)	0.004 (2)	0.0117 (17)
N241	0.102 (3)	0.093 (2)	0.122 (3)	0.027 (2)	−0.012 (2)	0.024 (2)
C25	0.0620 (19)	0.0616 (17)	0.079 (2)	0.0029 (17)	0.0050 (18)	0.0144 (16)
C26	0.0650 (19)	0.0549 (16)	0.0761 (19)	−0.0010 (15)	0.0116 (17)	0.0177 (16)
N31	0.0630 (15)	0.0452 (11)	0.0553 (13)	−0.0029 (12)	−0.0031 (12)	0.0001 (10)
C32	0.071 (2)	0.0632 (18)	0.076 (2)	−0.0159 (17)	−0.0082 (18)	0.0068 (16)
C33	0.093 (3)	0.0611 (18)	0.077 (2)	−0.019 (2)	0.002 (2)	0.0012 (17)
C34	0.100 (3)	0.0546 (17)	0.094 (2)	−0.012 (2)	−0.008 (2)	0.0097 (18)
C35	0.085 (2)	0.0445 (14)	0.075 (2)	0.0007 (16)	−0.0017 (19)	−0.0044 (14)
O1W	0.119 (2)	0.136 (2)	0.0643 (13)	−0.069 (2)	−0.0188 (15)	0.0232 (15)

Geometric parameters (Å, º)

C1—C2	1.520 (4)	C16—C20	1.335 (4)
C1—C10	1.536 (4)	C16—C17	1.523 (4)
C1—H1A	0.9700	C17—O17	1.409 (4)
C1—H1B	0.9700	C17—H17	0.9800
C2—C3	1.533 (4)	O17—H17A	0.8200
C2—H2A	0.9700	C18—H18A	0.9600
C2—H2B	0.9700	C18—H18B	0.9600
C3—N31	1.466 (3)	C18—H18C	0.9600
C3—C4	1.525 (4)	C19—H19A	0.9600
C3—H3	0.9800	C19—H19B	0.9600
C4—C5	1.514 (4)	C19—H19C	0.9600
C4—H4A	0.9700	C20—C21	1.462 (4)
C4—H4B	0.9700	C20—H20	0.9300
C5—C6	1.332 (4)	C21—C26	1.394 (4)
C5—C10	1.513 (4)	C21—C22	1.398 (4)
C6—C7	1.491 (4)	C22—C23	1.371 (4)
C6—H6	0.9300	C22—H22	0.9300
C7—C8	1.525 (4)	C23—C24	1.380 (5)
C7—H7A	0.9700	C23—H23	0.9300
C7—H7B	0.9700	C24—C25	1.390 (4)
C8—C14	1.519 (3)	C24—C241	1.439 (5)
C8—C9	1.536 (4)	C241—N241	1.135 (5)
C8—H8	0.9800	C25—C26	1.374 (4)
C9—C11	1.551 (4)	C25—H25	0.9300
C9—C10	1.551 (4)	C26—H26	0.9300
C9—H9	0.9800	N31—C35	1.469 (4)
C10—C19	1.536 (4)	N31—C32	1.481 (4)
C11—C12	1.525 (4)	C32—C33	1.505 (4)
C11—H11A	0.9700	C32—H32A	0.97
C11—H11B	0.9700	C32—H32B	0.97
C12—C13	1.519 (4)	C33—C34	1.501 (5)
C12—H12A	0.9700	C33—H33A	0.97
C12—H12B	0.9700	C33—H33B	0.97
C13—C18	1.529 (4)	C34—C35	1.516 (5)
C13—C17	1.536 (4)	C34—H34A	0.97
C13—C14	1.538 (4)	C34—H34B	0.97
C14—C15	1.533 (4)	C35—H35A	0.97
C14—H14	0.9800	C35—H35B	0.97
C15—C16	1.517 (4)	O1W—H1W	0.81
C15—H15A	0.9700	O1W—H2W	0.97
C15—H15B	0.9700
C2—C1—C10	114.2 (2)	C16—C15—C14	103.2 (2)
C2—C1—H1A	108.7	C16—C15—H15A	111.1
C10—C1—H1A	108.7	C14—C15—H15A	111.1
C2—C1—H1B	108.7	C16—C15—H15B	111.1
C10—C1—H1B	108.7	C14—C15—H15B	111.1
H1A—C1—H1B	107.6	H15A—C15—H15B	109.1
C1—C2—C3	112.0 (3)	C20—C16—C15	131.0 (3)
C1—C2—H2A	109.2	C20—C16—C17	121.3 (3)
C3—C2—H2A	109.2	C15—C16—C17	107.7 (2)
C1—C2—H2B	109.2	O17—C17—C16	112.6 (2)
C3—C2—H2B	109.2	O17—C17—C13	118.4 (3)
H2A—C2—H2B	107.9	C16—C17—C13	102.8 (2)
N31—C3—C4	111.3 (3)	O17—C17—H17	107.5
N31—C3—C2	110.2 (2)	C16—C17—H17	107.5
C4—C3—C2	109.6 (2)	C13—C17—H17	107.5
N31—C3—H3	108.6	C17—O17—H17A	109.5
C4—C3—H3	108.6	C13—C18—H18A	109.5
C2—C3—H3	108.6	C13—C18—H18B	109.5
C5—C4—C3	112.2 (3)	H18A—C18—H18B	109.5
C5—C4—H4A	109.2	C13—C18—H18C	109.5
C3—C4—H4A	109.2	H18A—C18—H18C	109.5
C5—C4—H4B	109.2	H18B—C18—H18C	109.5
C3—C4—H4B	109.2	C10—C19—H19A	109.5
H4A—C4—H4B	107.9	C10—C19—H19B	109.5
C6—C5—C10	123.5 (3)	H19A—C19—H19B	109.5
C6—C5—C4	119.9 (3)	C10—C19—H19C	109.5
C10—C5—C4	116.6 (2)	H19A—C19—H19C	109.5
C5—C6—C7	124.4 (3)	H19B—C19—H19C	109.5
C5—C6—H6	117.8	C16—C20—C21	130.2 (3)
C7—C6—H6	117.8	C16—C20—H20	114.9
C6—C7—C8	111.8 (2)	C21—C20—H20	114.9
C6—C7—H7A	109.2	C26—C21—C22	117.2 (3)
C8—C7—H7A	109.2	C26—C21—C20	125.1 (3)
C6—C7—H7B	109.2	C22—C21—C20	117.7 (3)
C8—C7—H7B	109.2	C23—C22—C21	121.5 (3)
H7A—C7—H7B	107.9	C23—C22—H22	119.3
C14—C8—C7	110.8 (2)	C21—C22—H22	119.3
C14—C8—C9	110.4 (2)	C22—C23—C24	120.3 (3)
C7—C8—C9	109.1 (2)	C22—C23—H23	119.8
C14—C8—H8	108.9	C24—C23—H23	119.8
C7—C8—H8	108.9	C23—C24—C25	119.4 (3)
C9—C8—H8	108.9	C23—C24—C241	120.7 (3)
C8—C9—C11	112.7 (2)	C25—C24—C241	120.0 (3)
C8—C9—C10	112.6 (2)	N241—C241—C24	179.4 (5)
C11—C9—C10	113.2 (2)	C26—C25—C24	120.0 (3)
C8—C9—H9	105.8	C26—C25—H25	120.0
C11—C9—H9	105.8	C24—C25—H25	120.0
C10—C9—H9	105.8	C25—C26—C21	121.5 (3)
C5—C10—C19	108.9 (2)	C25—C26—H26	119.2
C5—C10—C1	106.9 (2)	C21—C26—H26	119.2
C19—C10—C1	109.7 (2)	C3—N31—C35	113.0 (2)
C5—C10—C9	110.7 (2)	C3—N31—C32	114.4 (2)
C19—C10—C9	111.1 (2)	C35—N31—C32	103.4 (2)
C1—C10—C9	109.5 (2)	N31—C32—C33	103.8 (3)
C12—C11—C9	113.0 (2)	N31—C32—H32A	111.0
C12—C11—H11A	109.0	C33—C32—H32A	111.0
C9—C11—H11A	109.0	N31—C32—H32B	111.0
C12—C11—H11B	109.0	C33—C32—H32B	111.0
C9—C11—H11B	109.0	H32A—C32—H32B	109.0
H11A—C11—H11B	107.8	C34—C33—C32	105.0 (3)
C13—C12—C11	111.1 (2)	C34—C33—H33A	110.7
C13—C12—H12A	109.4	C32—C33—H33A	110.7
C11—C12—H12A	109.4	C34—C33—H33B	110.7
C13—C12—H12B	109.4	C32—C33—H33B	110.7
C11—C12—H12B	109.4	H33A—C33—H33B	108.8
H12A—C12—H12B	108.0	C33—C34—C35	106.0 (3)
C12—C13—C18	112.0 (2)	C33—C34—H34A	110.5
C12—C13—C17	115.7 (2)	C35—C34—H34A	110.5
C18—C13—C17	109.4 (2)	C33—C34—H34B	110.5
C12—C13—C14	107.3 (2)	C35—C34—H34B	110.5
C18—C13—C14	113.1 (2)	H34A—C34—H34B	108.7
C17—C13—C14	98.8 (2)	N31—C35—C34	104.6 (3)
C8—C14—C15	119.5 (2)	N31—C35—H35A	110.8
C8—C14—C13	114.3 (2)	C34—C35—H35A	110.8
C15—C14—C13	104.1 (2)	N31—C35—H35B	110.8
C8—C14—H14	106.0	C34—C35—H35B	110.8
C15—C14—H14	106.0	H35A—C35—H35B	108.9
C13—C14—H14	106.0	H1W—O1W—H2W	104
C10—C1—C2—C3	−56.9 (4)	C18—C13—C14—C15	−68.6 (3)
C1—C2—C3—N31	176.5 (3)	C17—C13—C14—C15	46.9 (3)
C1—C2—C3—C4	53.7 (4)	C8—C14—C15—C16	−160.3 (2)
N31—C3—C4—C5	−173.6 (2)	C13—C14—C15—C16	−31.3 (3)
C2—C3—C4—C5	−51.5 (4)	C14—C15—C16—C20	−178.2 (3)
C3—C4—C5—C6	−128.9 (3)	C14—C15—C16—C17	2.9 (3)
C3—C4—C5—C10	53.9 (4)	C20—C16—C17—O17	−24.1 (4)
C10—C5—C6—C7	−0.7 (5)	C15—C16—C17—O17	154.9 (3)
C4—C5—C6—C7	−177.7 (3)	C20—C16—C17—C13	−152.7 (3)
C5—C6—C7—C8	19.5 (4)	C15—C16—C17—C13	26.3 (3)
C6—C7—C8—C14	−169.5 (2)	C12—C13—C17—O17	76.9 (4)
C6—C7—C8—C9	−47.9 (3)	C18—C13—C17—O17	−50.6 (4)
C14—C8—C9—C11	−47.3 (3)	C14—C13—C17—O17	−169.0 (3)
C7—C8—C9—C11	−169.2 (2)	C12—C13—C17—C16	−158.1 (3)
C14—C8—C9—C10	−176.9 (2)	C18—C13—C17—C16	74.3 (3)
C7—C8—C9—C10	61.2 (3)	C14—C13—C17—C16	−44.1 (3)
C6—C5—C10—C19	−110.6 (3)	C15—C16—C20—C21	3.6 (5)
C4—C5—C10—C19	66.5 (3)	C17—C16—C20—C21	−177.7 (3)
C6—C5—C10—C1	131.0 (3)	C16—C20—C21—C26	−8.7 (5)
C4—C5—C10—C1	−51.9 (3)	C16—C20—C21—C22	171.0 (3)
C6—C5—C10—C9	11.9 (4)	C26—C21—C22—C23	2.8 (4)
C4—C5—C10—C9	−171.1 (2)	C20—C21—C22—C23	−176.9 (3)
C2—C1—C10—C5	52.9 (3)	C21—C22—C23—C24	−1.7 (5)
C2—C1—C10—C19	−65.0 (4)	C22—C23—C24—C25	0.4 (5)
C2—C1—C10—C9	172.8 (3)	C22—C23—C24—C241	−179.7 (3)
C8—C9—C10—C5	−42.0 (3)	C23—C24—C241—N241	87 (52)
C11—C9—C10—C5	−171.4 (2)	C25—C24—C241—N241	−93 (52)
C8—C9—C10—C19	79.2 (3)	C23—C24—C25—C26	−0.2 (5)
C11—C9—C10—C19	−50.2 (3)	C241—C24—C25—C26	179.9 (3)
C8—C9—C10—C1	−159.6 (2)	C24—C25—C26—C21	1.3 (5)
C11—C9—C10—C1	71.1 (3)	C22—C21—C26—C25	−2.6 (5)
C8—C9—C11—C12	49.0 (3)	C20—C21—C26—C25	177.1 (3)
C10—C9—C11—C12	178.3 (3)	C4—C3—N31—C35	−169.8 (3)
C9—C11—C12—C13	−55.6 (4)	C2—C3—N31—C35	68.4 (3)
C11—C12—C13—C18	−65.7 (3)	C4—C3—N31—C32	−51.8 (3)
C11—C12—C13—C17	168.1 (3)	C2—C3—N31—C32	−173.6 (3)
C11—C12—C13—C14	59.0 (3)	C3—N31—C32—C33	−165.0 (3)
C7—C8—C14—C15	−60.1 (3)	C35—N31—C32—C33	−41.6 (3)
C9—C8—C14—C15	179.0 (2)	N31—C32—C33—C34	29.3 (4)
C7—C8—C14—C13	175.8 (2)	C32—C33—C34—C35	−6.4 (4)
C9—C8—C14—C13	54.9 (3)	C3—N31—C35—C34	161.7 (3)
C12—C13—C14—C8	−60.5 (3)	C32—N31—C35—C34	37.4 (3)
C18—C13—C14—C8	63.4 (3)	C33—C34—C35—N31	−19.1 (4)
C17—C13—C14—C8	179.0 (2)	C19—C10—C13—C18	12.4 (3)
C12—C13—C14—C15	167.4 (2)	H8—C8—C9—H9	−172.6

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1W—H1W···N241^i	0.81	2.20	3.008 (5)	176
O1W—H2W···N31^ii	0.97	1.93	2.892 (3)	168
O17—H17A···O1W^iii	0.82	1.97	2.740 (4)	155

Symmetry codes: (i) x−1/2, −y−3/2, −z−1; (ii) −x, y−1/2, −z−3/2; (iii) x−1, y, z.