7-Hydr­oxy-5-meth­oxy-6,8-dimethyl­flavanone: a natural flavonoid

The title flavonoid [systematic name: (2S)-7-hydr­oxy-5-meth­oxy-6,8-dimethyl-2-phenyl-3,4-dihydro­chromen-4(2H)-one], C₁₈H₁₈O₄, displays statistical conformational disorder, with three conformations of the mol­ecule involving three orientations of the phenyl ring and two orientations of the fused heterocyclic ring. The conformational disorder is correlated with the isomerization equilibrium between the flavanone and chalcone forms. The conformational behaviour has a potential impact on the biological activity of this class of compounds. Moreover, [pi] stacking inter­actions at van der Waals distances are present between the aromatic rings of chroman-4-one groups of symmetry-related mol­ecules. Apart from these [pi]-[pi] inter­actions, mol­ecules are linked by strong O-H...O hydrogen bonds between hydr­oxy and carbonyl groups.

S1. Comment

Flavonoids are of interest because of their antioxidant activity (Pietta, 2000). However, it is now known that the health benefits they provide against cancer and heart disease are the result of other mechanisms (Dixon, 1999; Rice-Evans et al., 1996). More than 5000 different flavonoids have been characterized from various plants and classified according to their chemical structure (Ververidis et al., 2007). Flavanones are one of the subgroups. The title compound, (I), is a natural flavanone isolated from the leaves of the South American tree Couroupita guianensis. It was previously reported as an antihyperglycaemic agent (Hanshella et al., 2005).

The two most similar structures reported in the Cambridge Structural Database (CSD; Allen, 2002), (-)-6-bromocryptostrobin (Byrne et al., 1982) and 6,8-dimethylpinocembrin (Tanrisever et al., 1987), contain a disordered phenyl group. In our case, it was necessary to include three different disordered conformations (labeled A, B and C in Fig. 1) involving three orientations of the phenyl ring and two orientations of the connected cyclohexyl ring in order to obtain a good refinement. According to the (1 - x, -y, 1 - z) symmetry operation, conformation A by itself would exhibit overly short intermolecular contacts. Obviously these contacts cannot be real and we must consider these three conformations to correspond to a statistical disorder behaviour (Fig. 2a). The classical Cremer & Pople (1975) analysis of the heterocyclic nonplanar ring gives the ring-puckering parameters ϕ = 286.6 (5)° and θ = 53.9 (5)° and the puckering amplitude Q = 0.498 (5) Å for conformations A and C, and ϕ = 87.9 (10)°, θ = 131.0 (10)° and Q = 0.521 (13) Å for conformation B. Thus the ring conformation varies between the envelope (E) for A and C and the symmetrical half-chair (H) for B. Such a pattern of conformational equilibrium for flavanone derivatives has been described in solution (Toth et al., 2001) but not in the solid state as far we could find for previously reported flavanone derivatives. This behaviour seems to be associated with the isomerization equilibrium between the flavanone and chalcone forms (Gonzalez et al., 2002). On this basis, (I) should be a good precursor for the chalcone opened chemical form, which has been reported as an antitumor agent (Ye et al., 2005).

The structures of a number of flavanones (derived from 2,3-dihydro-2-phenylchromen-4-one) have been reported to the CSD. We can estimate the concordance between some internal geometric parameters of our structure and the data from 82 structures that include the flavanone chemical skeleton. In Fig. 3 we can see good concordance between some torsion angle values of the two statistical conformations A and C of (I). It is of note that each torsion angle displays a bimodal distribution, indicating that the two conformations of the above-mentioned heterocyclic nonplanar ring are almost equally probable in flavanones. This behaviour suggests that the involved bonds are in movement, hence the isomerization equilibrium should be usual for flavanones.

The molecules of (I) are linked by O—H···O hydrogen bonds between the hydroxy group of one molecule and the carbonyl O atom of an adjacent molecule to form chains running along the b axis (Fig. 2b). The crystal stability of (I) seems to be enhanced by intermolecular weak interactions. Classical π–π contacts are present between the aromatic rings of neighbouring chroman-4-one groups (Table 3). These interactions generate stacked molecules running almost parallel to the [001] crystal plane (Fig. 2c). This type of interaction seems to be common in flavanones since 11 of the 82 structures in the CSD display geometric parameters giving optimal π–π binding energy (McGaughey et al., 1998), i.e. the aromatic rings stack almost parallel (with a dihedral angle between stacking planes of less than 1°) with centroid–ring distances less than 4 Å as in (I).

The strategy of self-assembly through these weak and strong interactions is of central importance for efficient and specific biological reactions, and for the design of new supramolecules possessing interesting physical or chemical properties. As an example, despite the fact that (I) exhibits a high degree of disorder, the crystals were stable and their diffraction was good. This behaviour has encouraged us to undertake a polymorph screening, in order to obtain different types of solid state and, therefore, different types of biochemical behaviour. Such studies will be reported in future publications.

Related literature

For related literature, see: Altomare et al. (1999); Bruker (2001, 2007); Rice-Evans et al. (1996); Cremer & Pople (1975); Dixon (1999); Gonzalez et al. (2002); Farrugia (1997, 1999); Toth et al. (2001); McGaughey et al. (1998); Hanshella et al. (2005); Byrne et al. (1982); Macrae et al. (2006); Tanrisever et al. (1987); Pietta (2000); Sheldrick (2008); Spek (2003); Ververidis et al. (2007).

S2. Experimental

Compound (I) was obtained by purification of the hydroethanolic extract of the leaves of C. guianensis, using dichloromethane extraction and a silica-gel chromatographic column. Single crystals were obtained by evaporation from a chloroform solution. ¹H NMR (CDCl₃, 500.14 MHz, p.p.m.): δ 7.483–7.357 (m, 5H, Ar), 5.382 (dd, J = 13.1 and 2.8 Hz, 1H, –CH), 5.339 (s, 1H, –OH), 3.810 (s, 3H, –OCH₃), 2.968 (dd, J = 16.6 and 13.1 Hz, 1H, –CHH), 2.829 (dd, J = 16.6, 2.8 Hz, 1H, –CHH), 2.139 (s, 3H, –CH₃), 2.135 (s, 3H, –CH₃). ¹³C NMR (CDCl₃, 125.77 MHz, p.p.m.): δ 189.7 (C═O), 159.6 (C—OH), 158.8 (C—O), 157.7 (C—O), 139.2 (C), 128.7 (2 × CH, Ar), 128.4 (CH, Ar), 125.8 (2 × CH, Ar), 111.2 (C), 109.1 (C—Me), 106.9 (C—Me), 78.6 (O—CH), 61.3 (–OCH₃), 45.7 (CH₂), 8.1 (–CH₃), 7.9 (–CH₃). EI/MS: m/e 298 [(M)⁺, 21].

S3. Refinement

The hydroxy atom H21 was located in a difference map and refined isotropically. All other H atoms were positioned geometrically and included as riding atoms, with C—H distances in the range 0.95–1.00 Å and U_iso(H) values of 1.2 or 1.5 times U_eq(C). It was necessary to include a disordered model with three orientations, designated A, B and C, at occupancies of 43, 30 and 27%, respectively. Geometric calculations: PLATON (Spek, 2003).

Computing details

Data collection: APEX2 (Bruker, 2007); cell refinement: APEX2 (Bruker, 2007); data reduction: APEX2 (Bruker, 2007); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Macrae et al., 2006); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures

	Fig. 1. The atom-labelling scheme of (I). Displacement ellipsoids are drawn at the 50% probability level. The suffixes A, B and C denote the respective conformations. H atoms have been omitted for clarity.
	Fig. 2. (a) Intermolecular short contacts between one molecule of conformation A of (I) (grey coloured) and another molecule with the same conformation at (1 - x, -y, 1 - z). (b) The crystal packing of (I), showing the hydrogen-bond network (in red in the online version of the journal). (c) The aromatic cycles that constitute the weak intermolecular π–π interactions, and their calculated centroids where highlighted. (Conformations B and C are coloured blue and green, respectively, in the online verison of the journal.)
	Fig. 3. The frequencies of torsion angle values from CSD data. Each torsion angle corresponds to the highlighted atoms on the flavanone skeleton shown in each graph. The CSD search was related to the mentioned flavanone's chemical scheme. A and C symbols indicate the calculated angles corresponding to conformations A and C of (I), respectively.

(2S)-7-hydroxy-5-methoxy-6,8-dimethyl-2-phenyl-3,4-dihydrochromen-4(2H)-one

Crystal data

C18H18O4	F(000) = 632
Mr = 298.32	Dx = 1.323 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.7107 Å
Hall symbol: -P 2ybc	Cell parameters from 1983 reflections
a = 12.6503 (5) Å	θ = 2.9–23.7°
b = 17.1770 (5) Å	µ = 0.09 mm^−1
c = 7.1379 (3) Å	T = 100 K
β = 105.009 (2)°	Prism, colourless
V = 1498.11 (10) Å^3	0.14 × 0.11 × 0.02 mm
Z = 4

Data collection

Bruker APEXII CCD diffractometer	3189 independent reflections
Radiation source: fine-focus sealed tube	1994 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.091
ω and ϕ scans	θmax = 26.5°, θmin = 1.7°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −15→15
Tmin = 0.809, Tmax = 0.998	k = 0→21
30663 measured reflections	l = 0→8

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.066	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.170	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0492P)^2 + 2.1395P] where P = (Fo^2 + 2Fc^2)/3
3076 reflections	(Δ/σ)max < 0.001
230 parameters	Δρmax = 0.24 e Å^−3
0 restraints	Δρmin = −0.22 e Å^−3

Special details

Experimental. Geometric calculations: PLATON (Spek, 2003); RMN measurement: Bruker AMX500 500 MHz; Mass spectrometer: HP5988A, triple quadrupole ionization electrospray.

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	Occ. (<1)
O1	0.19369 (15)	0.06337 (11)	0.3318 (3)	0.0196 (5)
C2	0.2300 (3)	0.1397 (2)	0.2946 (7)	0.0191 (9)	0.43
H2	0.2005	0.1517	0.1536	0.023*	0.43
C3	0.1831 (5)	0.1970 (4)	0.4107 (7)	0.0224 (13)	0.43
H3A	0.2082	0.2502	0.3900	0.027*	0.43
H3B	0.2097	0.1846	0.5504	0.027*	0.43
C2B	0.2381 (8)	0.1375 (5)	0.4318 (17)	0.0191 (9)	0.30
H2B	0.2329	0.1359	0.5692	0.023*	0.30
C3B	0.1716 (14)	0.2048 (10)	0.328 (2)	0.0224 (13)	0.30
H3B1	0.2029	0.2548	0.3860	0.027*	0.30
H3B2	0.1711	0.2047	0.1891	0.027*	0.30
C2C	0.2300 (3)	0.1397 (2)	0.2946 (7)	0.0191 (9)	0.27
H2C	0.2005	0.1517	0.1536	0.023*	0.27
C3C	0.1831 (5)	0.1970 (4)	0.4107 (7)	0.0224 (13)	0.27
H3C1	0.2082	0.2502	0.3900	0.027*	0.27
H3C2	0.2097	0.1846	0.5504	0.027*	0.27
C4	0.0577 (2)	0.19442 (16)	0.3505 (4)	0.0183 (6)
C5	−0.1017 (2)	0.09941 (16)	0.2609 (4)	0.0157 (6)
C6	−0.1418 (2)	0.02469 (16)	0.2174 (4)	0.0167 (6)
C7	−0.0655 (2)	−0.03524 (15)	0.2194 (4)	0.0158 (6)
C8	0.0463 (2)	−0.02230 (15)	0.2587 (4)	0.0158 (6)
C9	0.0826 (2)	0.05430 (16)	0.2970 (4)	0.0157 (6)
C10	0.0109 (2)	0.11688 (16)	0.3007 (4)	0.0160 (6)
C11	0.3528 (5)	0.1383 (3)	0.3411 (8)	0.0201 (12)	0.43
C12	0.4090 (6)	0.1962 (5)	0.2775 (13)	0.0320 (18)	0.43
H12	0.3689	0.2372	0.2021	0.038*	0.43
C13	0.5210 (6)	0.1974 (5)	0.3180 (13)	0.0319 (9)	0.43
H13	0.5571	0.2391	0.2728	0.038*	0.43
C14	0.5801 (13)	0.1385 (7)	0.423 (2)	0.0319 (9)	0.43
H14	0.6574	0.1378	0.4436	0.038*	0.43
C15	0.5298 (6)	0.0796 (5)	0.5017 (13)	0.0319 (9)	0.43
H15	0.5723	0.0405	0.5809	0.038*	0.43
C16	0.4160 (6)	0.0786 (5)	0.4624 (13)	0.0336 (17)	0.43
H16	0.3803	0.0389	0.5153	0.040*	0.43
C11B	0.3604 (14)	0.1387 (10)	0.4286 (19)	0.0201 (12)	0.30
C12B	0.3834 (12)	0.1428 (7)	0.243 (3)	0.0320 (18)	0.30
H12B	0.3255	0.1442	0.1274	0.038*	0.30
C13B	0.4924 (10)	0.1444 (7)	0.234 (2)	0.0319 (9)	0.30
H13B	0.5088	0.1424	0.1112	0.038*	0.30
C14B	0.577 (3)	0.1490 (18)	0.403 (5)	0.0319 (9)	0.30
H14B	0.6521	0.1528	0.4022	0.038*	0.30
C15B	0.5426 (10)	0.1475 (6)	0.580 (2)	0.0319 (9)	0.30
H15B	0.5966	0.1483	0.7001	0.038*	0.30
C16B	0.4335 (10)	0.1451 (7)	0.580 (2)	0.0336 (17)	0.30
H16B	0.4143	0.1483	0.7004	0.040*	0.30
C11C	0.3528 (5)	0.1383 (3)	0.3411 (8)	0.0201 (12)	0.27
C12C	0.4039 (12)	0.1609 (9)	0.188 (3)	0.0320 (18)	0.27
H12C	0.3617	0.1735	0.0607	0.038*	0.27
C13C	0.5205 (11)	0.1630 (9)	0.238 (3)	0.0319 (9)	0.27
H13C	0.5578	0.1809	0.1468	0.038*	0.27
C14C	0.5801 (13)	0.1385 (7)	0.423 (2)	0.0319 (9)	0.27
H14C	0.6576	0.1361	0.4489	0.038*	0.27
C15C	0.5365 (11)	0.1193 (8)	0.560 (2)	0.0319 (9)	0.27
H15C	0.5813	0.1058	0.6841	0.038*	0.27
C16C	0.4213 (12)	0.1183 (9)	0.524 (2)	0.0336 (17)	0.27
H16C	0.3893	0.1038	0.6257	0.040*	0.27
O17	0.00522 (16)	0.25329 (11)	0.3672 (3)	0.0230 (5)
O18	−0.17575 (15)	0.15664 (11)	0.2751 (3)	0.0184 (5)
C19	−0.2107 (2)	0.20555 (17)	0.1082 (4)	0.0233 (7)
H19A	−0.1468	0.2233	0.0665	0.035*
H19B	−0.2498	0.2507	0.1408	0.035*
H19C	−0.2596	0.1762	0.0029	0.035*
C20	−0.2624 (2)	0.00663 (17)	0.1665 (5)	0.0265 (8)
H20A	−0.3040	0.0552	0.1570	0.040*
H20B	−0.2786	−0.0264	0.2676	0.040*
H20C	−0.2831	−0.0207	0.0419	0.040*
O21	−0.10861 (16)	−0.10776 (11)	0.1803 (3)	0.0205 (5)
C22	0.1255 (2)	−0.08807 (16)	0.2605 (4)	0.0206 (7)
H22A	0.1265	−0.1227	0.3700	0.031*
H22B	0.1990	−0.0668	0.2738	0.031*
H22C	0.1026	−0.1174	0.1390	0.031*
H21	−0.061 (3)	−0.143 (2)	0.171 (5)	0.045 (11)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0137 (10)	0.0146 (10)	0.0286 (12)	−0.0010 (8)	0.0022 (9)	−0.0006 (9)
C2	0.0155 (18)	0.0171 (18)	0.024 (2)	−0.0047 (15)	0.004 (2)	−0.002 (2)
C3	0.018 (2)	0.018 (2)	0.030 (4)	−0.0020 (17)	0.005 (3)	0.001 (3)
C2B	0.0155 (18)	0.0171 (18)	0.024 (2)	−0.0047 (15)	0.004 (2)	−0.002 (2)
C3B	0.018 (2)	0.018 (2)	0.030 (4)	−0.0020 (17)	0.005 (3)	0.001 (3)
C2C	0.0155 (18)	0.0171 (18)	0.024 (2)	−0.0047 (15)	0.004 (2)	−0.002 (2)
C3C	0.018 (2)	0.018 (2)	0.030 (4)	−0.0020 (17)	0.005 (3)	0.001 (3)
C4	0.0187 (15)	0.0166 (15)	0.0206 (16)	0.0000 (12)	0.0066 (13)	−0.0014 (12)
C5	0.0167 (15)	0.0175 (14)	0.0136 (15)	0.0033 (11)	0.0052 (12)	0.0026 (11)
C6	0.0179 (15)	0.0176 (14)	0.0153 (16)	−0.0009 (12)	0.0057 (12)	0.0014 (12)
C7	0.0214 (15)	0.0133 (14)	0.0118 (15)	−0.0029 (12)	0.0030 (12)	0.0004 (11)
C8	0.0186 (15)	0.0150 (14)	0.0134 (15)	−0.0004 (11)	0.0038 (12)	−0.0002 (11)
C9	0.0132 (14)	0.0177 (14)	0.0151 (15)	−0.0006 (11)	0.0015 (12)	0.0012 (12)
C10	0.0198 (15)	0.0161 (14)	0.0120 (15)	−0.0010 (12)	0.0039 (12)	0.0011 (11)
C11	0.014 (2)	0.0181 (17)	0.023 (4)	0.0002 (14)	−0.005 (3)	0.000 (3)
C12	0.020 (3)	0.027 (4)	0.043 (5)	−0.005 (3)	−0.002 (3)	0.010 (3)
C13	0.0202 (14)	0.029 (3)	0.045 (2)	−0.0009 (16)	0.0062 (14)	−0.0051 (16)
C14	0.0202 (14)	0.029 (3)	0.045 (2)	−0.0009 (16)	0.0062 (14)	−0.0051 (16)
C15	0.0202 (14)	0.029 (3)	0.045 (2)	−0.0009 (16)	0.0062 (14)	−0.0051 (16)
C16	0.028 (3)	0.020 (4)	0.057 (5)	−0.002 (3)	0.020 (3)	−0.008 (3)
C11B	0.014 (2)	0.0181 (17)	0.023 (4)	0.0002 (14)	−0.005 (3)	0.000 (3)
C12B	0.020 (3)	0.027 (4)	0.043 (5)	−0.005 (3)	−0.002 (3)	0.010 (3)
C13B	0.0202 (14)	0.029 (3)	0.045 (2)	−0.0009 (16)	0.0062 (14)	−0.0051 (16)
C14B	0.0202 (14)	0.029 (3)	0.045 (2)	−0.0009 (16)	0.0062 (14)	−0.0051 (16)
C15B	0.0202 (14)	0.029 (3)	0.045 (2)	−0.0009 (16)	0.0062 (14)	−0.0051 (16)
C16B	0.028 (3)	0.020 (4)	0.057 (5)	−0.002 (3)	0.020 (3)	−0.008 (3)
C11C	0.014 (2)	0.0181 (17)	0.023 (4)	0.0002 (14)	−0.005 (3)	0.000 (3)
C12C	0.020 (3)	0.027 (4)	0.043 (5)	−0.005 (3)	−0.002 (3)	0.010 (3)
C13C	0.0202 (14)	0.029 (3)	0.045 (2)	−0.0009 (16)	0.0062 (14)	−0.0051 (16)
C14C	0.0202 (14)	0.029 (3)	0.045 (2)	−0.0009 (16)	0.0062 (14)	−0.0051 (16)
C15C	0.0202 (14)	0.029 (3)	0.045 (2)	−0.0009 (16)	0.0062 (14)	−0.0051 (16)
C16C	0.028 (3)	0.020 (4)	0.057 (5)	−0.002 (3)	0.020 (3)	−0.008 (3)
O17	0.0233 (11)	0.0147 (10)	0.0319 (13)	0.0000 (9)	0.0088 (10)	−0.0019 (9)
O18	0.0170 (10)	0.0168 (10)	0.0221 (11)	0.0048 (8)	0.0066 (9)	0.0042 (8)
C19	0.0262 (17)	0.0220 (16)	0.0192 (17)	0.0073 (13)	0.0014 (13)	0.0016 (13)
C20	0.0198 (16)	0.0208 (16)	0.037 (2)	−0.0015 (13)	0.0050 (15)	0.0007 (14)
O21	0.0186 (11)	0.0141 (10)	0.0297 (13)	−0.0010 (9)	0.0078 (9)	−0.0026 (9)
C22	0.0204 (16)	0.0174 (14)	0.0236 (17)	0.0012 (12)	0.0048 (13)	−0.0009 (12)

Geometric parameters (Å, º)

O1—C9	1.372 (3)	C14—C15	1.385 (13)
O1—C2	1.436 (4)	C14—H14	0.9500
O1—C2B	1.495 (10)	C15—C16	1.393 (10)
C2—C3	1.505 (8)	C15—H15	0.9500
C2—C11	1.502 (7)	C16—H16	0.9500
C2—H2	1.0000	C11B—C16B	1.23 (2)
C3—C4	1.533 (7)	C11B—C12B	1.431 (19)
C3—H3A	0.9900	C12B—C13B	1.396 (19)
C3—H3B	0.9900	C12B—H12B	0.9500
C2B—C3B	1.507 (18)	C13B—C14B	1.39 (4)
C2B—C11B	1.56 (2)	C13B—H13B	0.9500
C2B—H2B	1.0000	C14B—C15B	1.44 (3)
C3B—C4	1.502 (18)	C14B—H14B	0.9500
C3B—H3B1	0.9900	C15B—C16B	1.382 (17)
C3B—H3B2	0.9900	C15B—H15B	0.9500
C4—O17	1.232 (3)	C16B—H16B	0.9500
C4—C10	1.464 (4)	C12C—C13C	1.42 (2)
C5—O18	1.380 (3)	C12C—H12C	0.9500
C5—C6	1.386 (4)	C13C—H13C	0.9500
C5—C10	1.409 (4)	C15C—C16C	1.412 (19)
C6—C7	1.409 (4)	C15C—H15C	0.9500
C6—C20	1.506 (4)	C16C—H16C	0.9500
C7—O21	1.359 (3)	O18—C19	1.431 (3)
C7—C8	1.386 (4)	C19—H19A	0.9800
C8—C9	1.397 (4)	C19—H19B	0.9800
C8—C22	1.508 (4)	C19—H19C	0.9800
C9—C10	1.411 (4)	C20—H20A	0.9800
C11—C12	1.366 (10)	C20—H20B	0.9800
C11—C16	1.443 (10)	C20—H20C	0.9800
C12—C13	1.369 (10)	O21—H21	0.87 (4)
C12—H12	0.9500	C22—H22A	0.9800
C13—C14	1.366 (14)	C22—H22B	0.9800
C13—H13	0.9500	C22—H22C	0.9800
C9—O1—C2	115.6 (2)	C12—C13—C14	119.5 (9)
C9—O1—C2B	115.0 (4)	C12—C13—H13	120.2
O1—C2—C3	107.8 (4)	C14—C13—H13	120.2
O1—C2—C11	107.9 (4)	C15—C14—C13	121.4 (12)
C3—C2—C11	114.9 (4)	C15—C14—H14	119.3
O1—C2—H2	108.7	C13—C14—H14	119.3
C3—C2—H2	108.7	C14—C15—C16	119.0 (9)
C11—C2—H2	108.7	C14—C15—H15	120.5
C2—C3—C4	110.7 (4)	C16—C15—H15	120.5
C2—C3—H3A	109.5	C15—C16—C11	119.7 (7)
C4—C3—H3A	109.5	C15—C16—H16	120.1
C2—C3—H3B	109.5	C11—C16—H16	120.1
C4—C3—H3B	109.5	C16B—C11B—C12B	121.7 (15)
H3A—C3—H3B	108.1	C16B—C11B—C2B	120.7 (13)
O1—C2B—C3B	109.1 (9)	C12B—C11B—C2B	117.1 (12)
O1—C2B—C11B	104.9 (8)	C13B—C12B—C11B	118.8 (14)
C3B—C2B—C11B	114.4 (11)	C13B—C12B—H12B	120.6
O1—C2B—H2B	109.5	C11B—C12B—H12B	120.6
C3B—C2B—H2B	109.5	C14B—C13B—C12B	121 (2)
C11B—C2B—H2B	109.5	C14B—C13B—H13B	119.6
C4—C3B—C2B	106.5 (10)	C12B—C13B—H13B	119.6
C4—C3B—H3B1	110.4	C13B—C14B—C15B	115 (3)
C2B—C3B—H3B1	110.4	C13B—C14B—H14B	122.7
C4—C3B—H3B2	110.4	C15B—C14B—H14B	122.7
C2B—C3B—H3B2	110.4	C16B—C15B—C14B	122.3 (18)
H3B1—C3B—H3B2	108.6	C16B—C15B—H15B	118.9
O17—C4—C10	125.2 (3)	C14B—C15B—H15B	118.9
O17—C4—C3B	117.9 (7)	C11B—C16B—C15B	121.4 (15)
C10—C4—C3B	115.0 (7)	C11B—C16B—H16B	119.3
O17—C4—C3	119.6 (3)	C15B—C16B—H16B	119.3
C10—C4—C3	114.8 (3)	C13C—C12C—H12C	121.7
O18—C5—C6	117.4 (2)	C12C—C13C—H13C	120.2
O18—C5—C10	120.2 (2)	C16C—C15C—H15C	120.2
C6—C5—C10	122.3 (2)	C15C—C16C—H16C	119.3
C5—C6—C7	117.6 (2)	C5—O18—C19	115.3 (2)
C5—C6—C20	122.3 (2)	O18—C19—H19A	109.5
C7—C6—C20	120.0 (2)	O18—C19—H19B	109.5
O21—C7—C8	121.5 (2)	H19A—C19—H19B	109.5
O21—C7—C6	115.4 (2)	O18—C19—H19C	109.5
C8—C7—C6	123.0 (2)	H19A—C19—H19C	109.5
C7—C8—C9	117.2 (2)	H19B—C19—H19C	109.5
C7—C8—C22	121.5 (2)	C6—C20—H20A	109.5
C9—C8—C22	121.3 (2)	C6—C20—H20B	109.5
O1—C9—C8	114.3 (2)	H20A—C20—H20B	109.5
O1—C9—C10	122.9 (2)	C6—C20—H20C	109.5
C8—C9—C10	122.7 (2)	H20A—C20—H20C	109.5
C5—C10—C9	117.1 (2)	H20B—C20—H20C	109.5
C5—C10—C4	124.5 (2)	C7—O21—H21	113 (2)
C9—C10—C4	118.4 (2)	C8—C22—H22A	109.5
C12—C11—C16	117.4 (6)	C8—C22—H22B	109.5
C12—C11—C2	120.8 (5)	H22A—C22—H22B	109.5
C16—C11—C2	121.7 (5)	C8—C22—H22C	109.5
C11—C12—C13	122.7 (7)	H22A—C22—H22C	109.5
C11—C12—H12	118.7	H22B—C22—H22C	109.5
C13—C12—H12	118.7
C9—O1—C2—C3	55.2 (4)	C6—C5—C10—C9	−0.8 (4)
C2B—O1—C2—C3	−43.4 (7)	O18—C5—C10—C4	−2.6 (4)
C9—O1—C2—C11	179.9 (3)	C6—C5—C10—C4	−178.9 (3)
C2B—O1—C2—C11	81.3 (7)	O1—C9—C10—C5	179.5 (3)
O1—C2—C3—C4	−60.4 (4)	C8—C9—C10—C5	−0.8 (4)
C11—C2—C3—C4	179.3 (4)	O1—C9—C10—C4	−2.2 (4)
C9—O1—C2B—C3B	−49.6 (10)	C8—C9—C10—C4	177.4 (3)
C2—O1—C2B—C3B	50.6 (9)	O17—C4—C10—C5	1.3 (5)
C9—O1—C2B—C11B	−172.6 (7)	C3B—C4—C10—C5	−162.3 (6)
C2—O1—C2B—C11B	−72.3 (9)	C3—C4—C10—C5	173.1 (3)
O1—C2B—C3B—C4	64.1 (12)	O17—C4—C10—C9	−176.7 (3)
C11B—C2B—C3B—C4	−178.8 (9)	C3B—C4—C10—C9	19.6 (7)
C2B—C3B—C4—O17	145.2 (8)	C3—C4—C10—C9	−4.9 (4)
C2B—C3B—C4—C10	−49.9 (11)	O1—C2—C11—C12	164.3 (7)
C2B—C3B—C4—C3	44.9 (16)	C3—C2—C11—C12	−75.4 (8)
C2—C3—C4—O17	−151.5 (4)	O1—C2—C11—C16	−19.0 (7)
C2—C3—C4—C10	36.2 (5)	C3—C2—C11—C16	101.2 (7)
C2—C3—C4—C3B	−59 (2)	C16—C11—C12—C13	2.7 (13)
O18—C5—C6—C7	−174.6 (2)	C2—C11—C12—C13	179.4 (7)
C10—C5—C6—C7	1.9 (4)	C11—C12—C13—C14	1.0 (15)
O18—C5—C6—C20	6.2 (4)	C12—C13—C14—C15	−4.2 (18)
C10—C5—C6—C20	−177.3 (3)	C13—C14—C15—C16	3.5 (18)
C5—C6—C7—O21	178.5 (2)	C14—C15—C16—C11	0.3 (14)
C20—C6—C7—O21	−2.3 (4)	C12—C11—C16—C15	−3.3 (12)
C5—C6—C7—C8	−1.4 (4)	C2—C11—C16—C15	180.0 (6)
C20—C6—C7—C8	177.8 (3)	O1—C2B—C11B—C16B	−124.2 (15)
O21—C7—C8—C9	180.0 (3)	C3B—C2B—C11B—C16B	116.4 (17)
C6—C7—C8—C9	−0.2 (4)	O1—C2B—C11B—C12B	64.0 (16)
O21—C7—C8—C22	−0.2 (4)	C3B—C2B—C11B—C12B	−55.5 (18)
C6—C7—C8—C22	179.7 (3)	C16B—C11B—C12B—C13B	8 (3)
C2—O1—C9—C8	155.9 (3)	C2B—C11B—C12B—C13B	179.6 (11)
C2B—O1—C9—C8	−161.8 (5)	C11B—C12B—C13B—C14B	−6 (2)
C2—O1—C9—C10	−24.4 (4)	C12B—C13B—C14B—C15B	4 (3)
C2B—O1—C9—C10	17.9 (6)	C13B—C14B—C15B—C16B	−3 (3)
C7—C8—C9—O1	−179.0 (2)	C12B—C11B—C16B—C15B	−7 (2)
C22—C8—C9—O1	1.1 (4)	C2B—C11B—C16B—C15B	−178.9 (11)
C7—C8—C9—C10	1.3 (4)	C14B—C15B—C16B—C11B	5 (2)
C22—C8—C9—C10	−178.6 (3)	C6—C5—O18—C19	−100.4 (3)
O18—C5—C10—C9	175.5 (2)	C10—C5—O18—C19	83.1 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O21—H21···O17^i	0.87 (4)	1.96 (4)	2.784 (3)	158 (4)

Symmetry code: (i) −x, y−1/2, −z+1/2.