16[alpha],17[alpha]-Epoxy-20-oxopregn-5-en-3[beta]-yl acetate

The title compound, C₂₃H₃₂O₄, has a 3[beta] configuration, with the epoxy O atom at 16[alpha],17[alpha]. Rings A and C have slightly distorted chair conformations. Because of the presence of the C5=C6 double bond, ring B assumes an 8[beta],9[alpha]-half-chair conformation slightly distorted towards an 8[beta]-sofa. Ring D has a conformation close to a 14[alpha]-envelope. The acetoxy and acetyl substituents are twisted with respect to the average molecular plane of the steroid. The conformation of the mol­ecule is compared with that given by a quantum chemistry calculation using the RHF-AM1 (RHF = Roothaan Hartree-Fock) Hamiltonian model. Cohesion of the crystal can be attributed to van der Waals interactions and weak intermolecular C-H...O interactions, which link the mol­ecules head-to-tail along [101].

S1. Comment

16α,17α-Epoxy-20-oxopregnanes are key intermediates in the synthesis of important steroidal compounds, ranging from such powerful anticancer agents as the cephalostins (Kim et al., 1999) to steroidal metabolites (Moreno et al., 1998) which are associated with certain pathological situations such as adrenal carcinoma and congenital adrenal hyperplasia (Zeelen, 1990). The title compound, (I), was obtained from 20-oxopregna-5,16-dien-3β-yl acetate via the application of well known reactions (Kirk & Sá e Melo, 1979), namely, stereoselective epoxidation of the C16 double bond with hydrogen peroxide in alkaline conditions, which produces the simultaneous hydrolysis of the 3β-OAc, followed by reacetylation of the 3β-hydroxy group with acetic anhydride in pyridine. The present X-ray diffraction study was undertaken to determine the stereochemistry of the epoxy O atom, which was found to be 16α,17α. This work is part of an on-going project to study the conformation of intermolecular interactions of steroidal 16α,17α-epoxy ketones, namely those functionalized at C21 or at C15, aiming to clarify the effect of those substituents on the behaviour of the epoxide ring towards cleavage reactions (Moreno et al., 1993). \sch

An ORTEPII (Johnson, 1976) drawing of the molecule of (I) with the corresponding atomic numbering scheme and ring labels is shown in Fig. 1. A l l rings are fused trans. The distance between terminal C atoms, C21—C23, is 14.873 (4) Å, and that between terminal O atoms, O20—O22, is 11.898 (3) Å. Bond lengths and angles are within the range of expected values (Allen et al., 1987), with average values Csp³—Csp³ 1.531 (11), Csp³—Csp² 1.503 (9), Csp²═ Csp² 1.328 (3) and C═O 1.202 (8) Å. It is worth mentioning a small but significant asymmetry between the two C—O epoxy bond lengths [1.433 (3) and 1.453 (3) Å].

Rings A and C are slightly flattened, the mean values of their torsion angles being 53 (2) and 56 (2)°, respectively. Both ring conformations are close to chair, as shown by the values of the Cremer & Pople (1975) puckering parameters [ring A: Q = 0.544 (3) Å, and θ = 8.2 (3) and ϕ = 80 (2)°; ring C: Q = 0.578 (2) Å, and θ = 8.2 (2) and ϕ = 272.9 (17)°]. Thus, the presence of the acetoxy 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 [the sum of the valence angles around this atom is 360.0 (4)°]. Hence, ring B is highly distorted from the normal chair conformation, assuming instead an 8β,9α half-chair conformation slightly distorted towards an 8β-sofa [asymmetry parameters (Duax & Norton, 1975) ΔC₂[5,6] = 7.2 (3), ΔC_s(6) = 16.6 (2) and ΔC_s(7) = 43.2 (2)°]. The five-membered ring D assumes a 14α-envelope conformation, with puckering parameters q₂ = 0.384 (3) Å and ϕ₂ = 210.5 (4)° [pseudo-rotation (Altona et al., 1968) and asymmetry parameters Δ = -25.2 (5), ϕ_m = 39.2 (2), ΔC_s(14) = 4.4 (3) and ΔC₂(13,14) = 13.5 (3)°].

The 3β acetoxy group attached to ring A is planar. The C3—O3 bond is oriented equatorially and (-)antiperiplanar to the C3—C4 bond. The dihedral angle between the plane of the acetoxy group and the mean molecular plane is 56.09 (9)°, showing that this group is twisted around the C3—O3 bond. The dihedral angle between the plane defined by the epoxy group and the average molecular plane comprising rings A, B, C and D is 89.6 (1)°.

As reported by Hatzel et al. (1976) for the similar structure 16α,17α-epoxy-3β-hydroxypregn-5-en-20-one, we also found an unusual conformation of the substituent group at C17, where the C13—C17 bond almost eclipses the C20—O20 bond [C13—C17—C20—O20 - 7.1 (4)°], which can be attributed to the epoxide link on ring D. In a comparison study of the molecular structures of six corticosteroids with a similar side chain at C17 and with no epoxy rings, Weeks et al. (1973) report values close to 90°. The unusual eclipsed conformation may also be responsible for the relatively large value of the pseudo-torsion angle C19—C10—C13—C18 [10.4 (2)°], which measures the twist of the molecule and usually does not exceed 4.0°. Also, the 17β methyl-ketone group is not coplanar with the mean molecular plane, the dihedral angle being 26.70 (14)°.

In order to obtain better insight into the effect of the substituents on the equilibrium conformation of the molecule, we have performed a semi-empirical calculation using the RHF/SCF-AM1 Hamiltonian model. Intermolecular interactions are weak (see below), which would validate a comparison between the conformation of an isolated molecule, as given by the calculation, and that observed in the crystal. The calculations were performed using the computer program GAMESS (Schmidt et al., 1993). Tight conditions were applied for SCF convergence and location of the equilibrium geometry, the final electron-density variation and maximum energy gradient at the final cycle being 10^-6 atomic units. At the end of the geometry optimization the Hessian matrix was calculated to confirm that the stationary point was a true minimum and not a saddle point, and indeed positive frequencies were obtained for every vibrational normal mode.

The calculated geometry was in good agreement with the X-ray data; the mean deviations of bond distances and angles, excluding those involving H atoms, were 0.014 Å and 0.96°, respectively. The conformation of the steroid nucleus is well reproduced by the calculation, the average difference between the calculated and experimental endocyclic torsion angles being 1.8°, with a maximum deviation of 3.2° for the C8—C14—C13—C12 torsion angle involving the C/D ring junction. Also, at the minimum energy conformation, the 17β methyl-ketone group was found with an eclipsed conformation of the C13—C17 and C20—O20 bonds. The calculated C13—C17—C20—O20 torsion angle is 6.0°, which compares well in magnitude with the X-ray geometry, although the sign of the angle is opposite to that of the measured value. The fact that an eclipsed conformation is also found for the isolated molecule supports the interpretation that such a conformation is related to the steric interaction between the methyl-ketone group and the epoxide atom O16, rather than to intermolecular interactions or packing effects. However, weak intramolecular C—H···O interactions may also stabilize this particular conformation, as described below.

The equilibrium conformation of the 3β acetoxy group of the isolated molecule was found to be close to that observed in the crystal, the calculated and measured C4—C3—O3—C22 torsion angle being -156.3 and -161.4 (2)°, respectively, despite the presence of a close contact in the crystal between atoms O22 and C21 of neighbouring molecules. Moreover, the large pseudo-torsion angle C19—C10—C13—C18 is well reproduced by the calculation, which gave a value of 11.8°, in good agreement with the experimental value of 10.4°.

Cohesion of the structure of (I) is achieved mainly by van der Waals interactions. No classical hydrogen bonds are present in the structure, as the molecule lacks a strong hydrogen donor. Two intramolecular C—H···O short contacts between the O atoms of the epoxy and ketone groups and a neighbouring H atom of a methyl group are present: C21—H21B···O16 at 2.914 (4) Å and C18—H18A···O20 at 3.108 (3) Å. However, in view of the rather bent angles defined by these atoms of 104.7 and 114.1°, respectively, and the rather weak acidic character of the methyl group, these interactions are probably destabilizing and should not be qualified as weak hydrogen bonds. A search for intermolecular C—H···O close contacts shows that the sole probable interaction of this type is C21—H21C···O22ⁱ [3.482 (4) Å, 166.4°; symmetry code: (i) x - 1, y, z - 1], which links the molecules head-to-tail in chains parallel to the [101] direction.

Related literature

For related literature, see: Allen et al. (1987); Altona et al. (1968); Cremer & Pople (1975); Duax & Norton (1975); Hatzel et al. (1976); Johnson (1976); Kim et al. (1999); Kirk & Sá e Melo (1979); Moreno et al. (1993, 1998); Schmidt (1993); Sheldrick (1997); Spek (1995); Weeks et al. (1973); Zeelen (1990).

S2. Experimental

Oxidation of the commercially available 20-oxopregne-5,16-dien-3β-yl acetate to the 16α,17α-epoxy-3β-hydroxypregn-5-en-20-one with hydrogen peroxyde in alkaline conditions and subsequent esterification with acetic anhydride in pyridine were performed according to the literature method of Kirk & Sá e Melo (1979). The product of this two-step procedure was isolated in very good yields and identified as (I) from IR, ¹H NMR and ¹³C NMR spectra. Crystals suitable for X-ray analysis were obtained by slow evaporation of a solution of the steroid in methanol.

S3. Refinement

H atoms were placed at calculated positions and refined as riding, using the SHELXL97 (Sheldrick, 1997) defaults (C—H 0.93–0.98 Å). Because the molecule lacks the presence of a significant anomalous scatterer at the Mo Kα wavelength, Friedel pairs were merged and the correct enantiomer was choosen to agree with the known chirality of the steroid. Examination of the crystal structure with PLATON (Spek, 1995) showed that there is one small (14 ų) void in the asymmetric unit located at (0.055, 0.083, 0.764). The closest atoms to this void are the acetoxy atoms O22 and C23 of one molecule, at distances of 2.88 and 2.91 Å, respectively, and the two methyl atoms C18 and C19 of a neighbouring molecule, at 3.16 and 3.27 Å, respectively. However, both the volume and the small residual density at the void positions exclude the possibility of occupation of the void by a solvent molecule.

Computing details

Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: HELENA (Spek, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97; molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. The ORTEPII (Johnson, 1976) plot of (I). Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.

16α,17α-Epoxy-20-oxopregn-5-en-3β-yl acetate

Crystal data

C23H32O4	F(000) = 404
Mr = 372.49	Dx = 1.205 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 7.5950 (7) Å	Cell parameters from 25 reflections
b = 9.9731 (9) Å	θ = 10.1–19.3°
c = 13.7266 (9) Å	µ = 0.08 mm^−1
β = 98.967 (6)°	T = 293 K
V = 1027.02 (15) Å^3	Prism, colourless
Z = 2	0.58 × 0.49 × 0.12 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	Rint = 0.023
Radiation source: fine-focus sealed tube	θmax = 27.4°, θmin = 3.0°
Graphite monochromator	h = −9→9
profile data from ω/2θ scans	k = −12→0
5324 measured reflections	l = −17→17
2481 independent reflections	3 standard reflections every 180 min
1893 reflections with I > 2σ(I)	intensity decay: 2.6%

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)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.101	H-atom parameters constrained
S = 1.02	w = 1/[σ^2(Fo^2) + (0.0578P)^2 + 0.0846P] where P = (Fo^2 + 2Fc^2)/3
2481 reflections	(Δ/σ)max < 0.001
248 parameters	Δρmax = 0.19 e Å^−3
1 restraint	Δρmin = −0.17 e Å^−3

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
O3	1.5530 (2)	0.19743 (19)	0.67466 (11)	0.0506 (4)
O16	0.4637 (2)	0.0246 (2)	0.15074 (14)	0.0570 (5)
O20	0.3171 (3)	0.3518 (3)	0.10896 (19)	0.0780 (7)
O22	1.4259 (3)	0.1561 (3)	0.80778 (15)	0.0835 (7)
C1	1.0933 (3)	0.2786 (3)	0.53749 (16)	0.0464 (6)
H1A	1.0186	0.3573	0.5387	0.056*
H1B	1.0289	0.2027	0.5586	0.056*
C2	1.2634 (3)	0.2987 (3)	0.61098 (17)	0.0486 (6)
H2A	1.3250	0.3783	0.5936	0.058*
H2B	1.2337	0.3114	0.6766	0.058*
C3	1.3831 (3)	0.1785 (3)	0.61046 (16)	0.0436 (5)
H3	1.3232	0.0988	0.6313	0.052*
C4	1.4283 (3)	0.1565 (3)	0.50818 (16)	0.0472 (6)
H4A	1.4990	0.0756	0.5080	0.057*
H4B	1.4998	0.2311	0.4912	0.057*
C5	1.2633 (3)	0.1441 (2)	0.43109 (15)	0.0376 (5)
C6	1.2466 (3)	0.0431 (2)	0.36724 (16)	0.0417 (5)
H6	1.3363	−0.0212	0.3744	0.050*
C7	1.0949 (3)	0.0245 (2)	0.28482 (16)	0.0390 (5)
H7A	1.0253	−0.0525	0.2991	0.047*
H7B	1.1422	0.0058	0.2246	0.047*
C8	0.9725 (3)	0.1471 (2)	0.26831 (14)	0.0333 (4)
H8	1.0261	0.2142	0.2298	0.040*
C9	0.9460 (3)	0.2083 (2)	0.36816 (15)	0.0333 (4)
H9	0.9001	0.1361	0.4056	0.040*
C10	1.1244 (3)	0.2542 (2)	0.43003 (15)	0.0344 (5)
C11	0.8026 (3)	0.3193 (3)	0.35604 (17)	0.0437 (5)
H11A	0.7788	0.3448	0.4209	0.052*
H11B	0.8501	0.3974	0.3270	0.052*
C12	0.6268 (3)	0.2802 (3)	0.29258 (16)	0.0433 (5)
H12A	0.5678	0.2120	0.3262	0.052*
H12B	0.5491	0.3579	0.2827	0.052*
C13	0.6600 (3)	0.2269 (2)	0.19320 (16)	0.0369 (5)
C14	0.7899 (3)	0.1079 (2)	0.21333 (15)	0.0361 (5)
H14	0.7380	0.0489	0.2584	0.043*
C15	0.7708 (3)	0.0318 (3)	0.11516 (18)	0.0502 (6)
H15A	0.8433	0.0718	0.0707	0.060*
H15B	0.8033	−0.0618	0.1252	0.060*
C16	0.5740 (3)	0.0475 (3)	0.07665 (19)	0.0535 (6)
H16	0.5281	0.0285	0.0073	0.064*
C17	0.5033 (3)	0.1621 (3)	0.12665 (16)	0.0441 (5)
C18	0.7303 (3)	0.3378 (3)	0.13111 (19)	0.0490 (6)
H18A	0.6519	0.4138	0.1271	0.074*
H18B	0.7352	0.3044	0.0660	0.074*
H18C	0.8475	0.3642	0.1616	0.074*
C19	1.1949 (3)	0.3832 (3)	0.3882 (2)	0.0504 (6)
H19A	1.3158	0.3984	0.4188	0.076*
H19B	1.1223	0.4578	0.4015	0.076*
H19C	1.1907	0.3740	0.3183	0.076*
C20	0.3383 (3)	0.2374 (3)	0.08382 (19)	0.0513 (6)
C21	0.2023 (4)	0.1679 (4)	0.0106 (2)	0.0676 (9)
H21A	0.0922	0.2167	0.0034	0.101*
H21B	0.1837	0.0787	0.0333	0.101*
H21C	0.2439	0.1635	−0.0519	0.101*
C22	1.5549 (4)	0.1808 (3)	0.77120 (19)	0.0574 (7)
C23	1.7391 (5)	0.1959 (4)	0.8273 (2)	0.0805 (10)
H23A	1.7354	0.2511	0.8842	0.121*
H23B	1.8143	0.2371	0.7857	0.121*
H23C	1.7858	0.1092	0.8478	0.121*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O3	0.0538 (10)	0.0543 (11)	0.0403 (8)	−0.0046 (9)	−0.0034 (7)	0.0044 (8)
O16	0.0505 (10)	0.0507 (11)	0.0689 (11)	−0.0132 (9)	0.0066 (9)	−0.0025 (9)
O20	0.0592 (13)	0.0791 (17)	0.0884 (16)	0.0169 (12)	−0.0117 (11)	−0.0072 (13)
O22	0.0988 (17)	0.099 (2)	0.0525 (11)	−0.0202 (16)	0.0128 (11)	0.0134 (13)
C1	0.0448 (12)	0.0509 (14)	0.0436 (12)	0.0048 (11)	0.0068 (10)	−0.0148 (11)
C2	0.0531 (13)	0.0485 (15)	0.0428 (12)	0.0027 (12)	0.0031 (10)	−0.0148 (11)
C3	0.0465 (12)	0.0417 (13)	0.0403 (11)	−0.0048 (11)	−0.0003 (9)	−0.0004 (10)
C4	0.0432 (12)	0.0531 (15)	0.0437 (11)	0.0096 (12)	0.0022 (9)	−0.0041 (12)
C5	0.0371 (11)	0.0386 (12)	0.0375 (10)	0.0039 (10)	0.0072 (8)	−0.0002 (9)
C6	0.0439 (12)	0.0366 (12)	0.0444 (11)	0.0114 (10)	0.0060 (9)	−0.0021 (10)
C7	0.0439 (11)	0.0325 (12)	0.0413 (11)	0.0047 (10)	0.0090 (9)	−0.0048 (9)
C8	0.0352 (10)	0.0294 (10)	0.0359 (10)	0.0007 (9)	0.0073 (8)	−0.0015 (8)
C9	0.0354 (10)	0.0289 (11)	0.0365 (10)	0.0005 (8)	0.0085 (8)	−0.0021 (8)
C10	0.0359 (11)	0.0285 (11)	0.0389 (10)	0.0016 (9)	0.0057 (8)	−0.0037 (9)
C11	0.0433 (12)	0.0422 (13)	0.0451 (12)	0.0075 (11)	0.0050 (9)	−0.0108 (10)
C12	0.0370 (11)	0.0483 (14)	0.0454 (12)	0.0067 (11)	0.0084 (9)	−0.0043 (11)
C13	0.0327 (10)	0.0390 (13)	0.0387 (11)	0.0001 (9)	0.0041 (8)	−0.0004 (9)
C14	0.0408 (11)	0.0330 (11)	0.0348 (10)	−0.0022 (9)	0.0069 (9)	−0.0025 (8)
C15	0.0500 (13)	0.0513 (15)	0.0473 (13)	0.0023 (12)	0.0008 (11)	−0.0129 (12)
C16	0.0491 (13)	0.0589 (17)	0.0508 (13)	−0.0052 (13)	0.0025 (11)	−0.0152 (13)
C17	0.0413 (12)	0.0493 (14)	0.0418 (11)	−0.0052 (11)	0.0066 (9)	0.0015 (11)
C18	0.0493 (14)	0.0458 (15)	0.0516 (13)	−0.0001 (11)	0.0066 (11)	0.0113 (11)
C19	0.0472 (13)	0.0338 (12)	0.0678 (15)	−0.0081 (11)	0.0018 (12)	0.0032 (12)
C20	0.0401 (13)	0.0647 (19)	0.0486 (13)	0.0013 (12)	0.0055 (10)	0.0039 (13)
C21	0.0418 (13)	0.095 (3)	0.0626 (16)	−0.0057 (17)	−0.0034 (12)	0.0013 (18)
C22	0.0791 (19)	0.0458 (16)	0.0427 (12)	−0.0096 (15)	−0.0047 (12)	0.0069 (12)
C23	0.093 (2)	0.082 (2)	0.0565 (16)	−0.014 (2)	−0.0208 (16)	0.0140 (17)

Geometric parameters (Å, º)

O3—C22	1.333 (3)	C11—C12	1.527 (3)
O3—C3	1.457 (3)	C11—H11A	0.9700
O16—C16	1.433 (3)	C11—H11B	0.9700
O16—C17	1.453 (3)	C12—C13	1.521 (3)
O20—C20	1.209 (4)	C12—H12A	0.9700
O22—C22	1.194 (4)	C12—H12B	0.9700
C1—C2	1.523 (3)	C13—C17	1.526 (3)
C1—C10	1.549 (3)	C13—C14	1.541 (3)
C1—H1A	0.9700	C13—C18	1.542 (3)
C1—H1B	0.9700	C14—C15	1.534 (3)
C2—C3	1.505 (4)	C14—H14	0.9800
C2—H2A	0.9700	C15—C16	1.514 (3)
C2—H2B	0.9700	C15—H15A	0.9700
C3—C4	1.512 (3)	C15—H15B	0.9700
C3—H3	0.9800	C16—C17	1.477 (4)
C4—C5	1.514 (3)	C16—H16	0.9800
C4—H4A	0.9700	C17—C20	1.500 (4)
C4—H4B	0.9700	C18—H18A	0.9600
C5—C6	1.328 (3)	C18—H18B	0.9600
C5—C10	1.521 (3)	C18—H18C	0.9600
C6—C7	1.495 (3)	C19—H19A	0.9600
C6—H6	0.9300	C19—H19B	0.9600
C7—C8	1.531 (3)	C19—H19C	0.9600
C7—H7A	0.9700	C20—C21	1.495 (4)
C7—H7B	0.9700	C21—H21A	0.9600
C8—C14	1.523 (3)	C21—H21B	0.9600
C8—C9	1.542 (3)	C21—H21C	0.9600
C8—H8	0.9800	C22—C23	1.495 (4)
C9—C11	1.543 (3)	C23—H23A	0.9600
C9—C10	1.552 (3)	C23—H23B	0.9600
C9—H9	0.9800	C23—H23C	0.9600
C10—C19	1.539 (3)
C22—O3—C3	117.1 (2)	C11—C12—H12A	109.6
C16—O16—C17	61.56 (17)	C13—C12—H12B	109.6
C2—C1—C10	114.33 (18)	C11—C12—H12B	109.6
C2—C1—H1A	108.7	H12A—C12—H12B	108.1
C10—C1—H1A	108.7	C12—C13—C17	117.51 (19)
C2—C1—H1B	108.7	C12—C13—C14	107.43 (18)
C10—C1—H1B	108.7	C17—C13—C14	101.49 (19)
H1A—C1—H1B	107.6	C12—C13—C18	111.4 (2)
C3—C2—C1	110.04 (19)	C17—C13—C18	106.12 (19)
C3—C2—H2A	109.7	C14—C13—C18	112.61 (18)
C1—C2—H2A	109.7	C8—C14—C15	121.09 (18)
C3—C2—H2B	109.7	C8—C14—C13	113.54 (18)
C1—C2—H2B	109.7	C15—C14—C13	104.70 (18)
H2A—C2—H2B	108.2	C8—C14—H14	105.4
O3—C3—C2	111.86 (19)	C15—C14—H14	105.4
O3—C3—C4	105.81 (18)	C13—C14—H14	105.4
C2—C3—C4	110.1 (2)	C16—C15—C14	102.02 (19)
O3—C3—H3	109.7	C16—C15—H15A	111.4
C2—C3—H3	109.7	C14—C15—H15A	111.4
C4—C3—H3	109.7	C16—C15—H15B	111.4
C3—C4—C5	112.21 (18)	C14—C15—H15B	111.4
C3—C4—H4A	109.2	H15A—C15—H15B	109.2
C5—C4—H4A	109.2	O16—C16—C17	59.91 (16)
C3—C4—H4B	109.2	O16—C16—C15	113.0 (2)
C5—C4—H4B	109.2	C17—C16—C15	109.2 (2)
H4A—C4—H4B	107.9	O16—C16—H16	120.1
C6—C5—C4	120.5 (2)	C17—C16—H16	120.1
C6—C5—C10	123.10 (19)	C15—C16—H16	120.1
C4—C5—C10	116.41 (19)	O16—C17—C16	58.53 (18)
C5—C6—C7	125.2 (2)	O16—C17—C20	111.8 (2)
C5—C6—H6	117.4	C16—C17—C20	123.2 (2)
C7—C6—H6	117.4	O16—C17—C13	115.6 (2)
C6—C7—C8	113.07 (18)	C16—C17—C13	107.4 (2)
C6—C7—H7A	109.0	C20—C17—C13	123.3 (2)
C8—C7—H7A	109.0	C13—C18—H18A	109.5
C6—C7—H7B	109.0	C13—C18—H18B	109.5
C8—C7—H7B	109.0	H18A—C18—H18B	109.5
H7A—C7—H7B	107.8	C13—C18—H18C	109.5
C14—C8—C7	110.70 (18)	H18A—C18—H18C	109.5
C14—C8—C9	107.89 (15)	H18B—C18—H18C	109.5
C7—C8—C9	110.18 (16)	C10—C19—H19A	109.5
C14—C8—H8	109.3	C10—C19—H19B	109.5
C7—C8—H8	109.3	H19A—C19—H19B	109.5
C9—C8—H8	109.3	C10—C19—H19C	109.5
C8—C9—C11	112.08 (17)	H19A—C19—H19C	109.5
C8—C9—C10	112.29 (16)	H19B—C19—H19C	109.5
C11—C9—C10	112.89 (18)	O20—C20—C21	121.4 (3)
C8—C9—H9	106.3	O20—C20—C17	120.0 (3)
C11—C9—H9	106.3	C21—C20—C17	118.6 (3)
C10—C9—H9	106.3	C20—C21—H21A	109.5
C5—C10—C19	109.01 (18)	C20—C21—H21B	109.5
C5—C10—C1	108.24 (18)	H21A—C21—H21B	109.5
C19—C10—C1	109.7 (2)	C20—C21—H21C	109.5
C5—C10—C9	109.74 (17)	H21A—C21—H21C	109.5
C19—C10—C9	111.55 (18)	H21B—C21—H21C	109.5
C1—C10—C9	108.54 (17)	O22—C22—O3	124.1 (3)
C12—C11—C9	114.7 (2)	O22—C22—C23	124.6 (3)
C12—C11—H11A	108.6	O3—C22—C23	111.3 (3)
C9—C11—H11A	108.6	C22—C23—H23A	109.5
C12—C11—H11B	108.6	C22—C23—H23B	109.5
C9—C11—H11B	108.6	H23A—C23—H23B	109.5
H11A—C11—H11B	107.6	C22—C23—H23C	109.5
C13—C12—C11	110.38 (18)	H23A—C23—H23C	109.5
C13—C12—H12A	109.6	H23B—C23—H23C	109.5
C10—C1—C2—C3	−58.1 (3)	C7—C8—C14—C15	−53.6 (3)
C22—O3—C3—C2	78.6 (3)	C9—C8—C14—C15	−174.2 (2)
C22—O3—C3—C4	−161.4 (2)	C7—C8—C14—C13	−179.43 (17)
C1—C2—C3—O3	175.94 (18)	C9—C8—C14—C13	59.9 (2)
C1—C2—C3—C4	58.6 (3)	C12—C13—C14—C8	−63.6 (2)
O3—C3—C4—C5	−176.3 (2)	C17—C13—C14—C8	172.45 (17)
C2—C3—C4—C5	−55.2 (3)	C18—C13—C14—C8	59.4 (2)
C3—C4—C5—C6	−130.5 (2)	C12—C13—C14—C15	162.21 (19)
C3—C4—C5—C10	51.1 (3)	C17—C13—C14—C15	38.3 (2)
C4—C5—C6—C7	−176.5 (2)	C18—C13—C14—C15	−74.7 (2)
C10—C5—C6—C7	1.8 (4)	C8—C14—C15—C16	−165.9 (2)
C5—C6—C7—C8	10.1 (3)	C13—C14—C15—C16	−36.0 (3)
C6—C7—C8—C14	−158.91 (17)	C17—O16—C16—C15	99.6 (2)
C6—C7—C8—C9	−39.6 (2)	C14—C15—C16—O16	−44.6 (3)
C14—C8—C9—C11	−50.8 (2)	C14—C15—C16—C17	19.9 (3)
C7—C8—C9—C11	−171.75 (18)	C16—O16—C17—C20	116.5 (2)
C14—C8—C9—C10	−179.11 (18)	C16—O16—C17—C13	−95.5 (2)
C7—C8—C9—C10	59.9 (2)	C15—C16—C17—O16	−106.0 (2)
C6—C5—C10—C19	−105.6 (3)	O16—C16—C17—C20	−96.9 (3)
C4—C5—C10—C19	72.7 (2)	C15—C16—C17—C20	157.0 (2)
C6—C5—C10—C1	135.1 (2)	O16—C16—C17—C13	109.9 (2)
C4—C5—C10—C1	−46.5 (3)	C15—C16—C17—C13	3.8 (3)
C6—C5—C10—C9	16.8 (3)	C12—C13—C17—O16	−79.7 (3)
C4—C5—C10—C9	−164.81 (19)	C14—C13—C17—O16	37.1 (2)
C2—C1—C10—C5	50.0 (3)	C18—C13—C17—O16	154.92 (19)
C2—C1—C10—C19	−68.8 (3)	C12—C13—C17—C16	−142.6 (2)
C2—C1—C10—C9	169.1 (2)	C14—C13—C17—C16	−25.8 (2)
C8—C9—C10—C5	−47.2 (2)	C18—C13—C17—C16	92.1 (2)
C11—C9—C10—C5	−175.06 (17)	C12—C13—C17—C20	64.3 (3)
C8—C9—C10—C19	73.8 (2)	C14—C13—C17—C20	−179.0 (2)
C11—C9—C10—C19	−54.1 (2)	C18—C13—C17—C20	−61.1 (3)
C8—C9—C10—C1	−165.28 (19)	O16—C17—C20—O20	138.0 (3)
C11—C9—C10—C1	66.8 (2)	C16—C17—C20—O20	−156.2 (3)
C8—C9—C11—C12	50.0 (3)	C13—C17—C20—O20	−7.1 (4)
C10—C9—C11—C12	177.96 (18)	O16—C17—C20—C21	−41.7 (3)
C9—C11—C12—C13	−53.0 (3)	C16—C17—C20—C21	24.1 (4)
C11—C12—C13—C17	170.4 (2)	C13—C17—C20—C21	173.2 (2)
C11—C12—C13—C14	56.9 (3)	C3—O3—C22—O22	−2.6 (4)
C11—C12—C13—C18	−66.9 (3)	C3—O3—C22—C23	176.9 (2)