Ethyl 3β-hydroxy­pregna-5,17(20)-dien-21-oate

In the structure of the title steroid, C₂₃H₃₄O₃, the mol­ecules are linked in infinite chains through inter­molecular C₁¹(n) O—H...O hydrogen bonds between the hydr­oxy proton and the ester carbonyl O atom.

Key indicators

• Single-crystal X-ray study
• T = 295 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.041
• wR factor = 0.111
• Data-to-parameter ratio = 7.5

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) .....       7.47
PLAT155_ALERT_4_C The Triclinic Unitcell is NOT Reduced ..........          ?
PLAT340_ALERT_3_C Low Bond Precision on C-C bonds (x 1000) Ang ...          5

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           25.00
           From the CIF: _reflns_number_total               1756
           Count of symmetry unique reflns         1758
           Completeness (_total/calc)             99.89%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   3 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion

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S1. Comment

Recent research suggests that steroids such as ergosterol and fusidic acid display antitubercular activity (Ruggutt & Ruggutt, 2001). In fact, the minimum inhibitory concentration (MIC) for these steroids is comparable to a number of clinically used anti-TB drugs. This, as well as the structural similarity of the title compound, (II), with fusidic acid and ergosterol has prompted us to consider conjugation of this compound with a number of well known anti-TB agents (Ballell et al., 2005). Our aim is to increase the lipophilicity of the parent drug by attaching a steroid moiety which could have anti-TB activity in its own right. As part of this project, compound (II) was prepared from the commercially available ketone, dehydroandrosterone (I) (Verma et al., 2004), by the Wittig–Horner reaction (Wicha et al., 1977), and was recrystallized from methanol.

Compound (II) crystallizes in the space group P1 with one molecule in the unit cell. The fused tetracyclic ring system adopts the expected conformations for the all-transA/B/C/D junctions. The six-membered rings A and C adopt normal chair conformations. As previously observed in related structures (Thamotharan et al., 2004; Verma et al., 2004), the hydroxy group on C3 does not perturb the structure of ring A. The C5═C6 bond length of 1.326 (5) Å confirms the presence of the double bond in this position and imposes an 8β,9α-half-chair conformation on ring B. Ring D adopts the 14α-envelope conformation previously observed in the dehydroandrosterone parent (Verma et al., 2004); this conformation minimizes steric interactions with the angular C18 methyl group (Fuchs, 1978).

The C17═C20 bond length of 1.331 (5) Å confirms the presence of the double bond in this position. The substitutents on this bond adopt the thermodynamically favoured E configuration which, again, minimizes interactions with the angular methyl group. The C20—C21 bond length of 1.460 (5) Å suggests partial double-bond character, with the ester group adopting an s-trans configuration. The molecules in the crystal structure are linked through intermolecular C₁¹(n) (Bernstein et al., 1995) O—H···O hydrogen bonds between the O3 hydroxy proton and the O21 carbonyl O atom (Table 2), forming infinite chains along the body diagonal of the unit cell.

The ¹H and ¹³C NMR spectra of the compound were fully assigned using two-dimensional gCOSY, gHSQC and gHMBC methods. The lowfield ¹³C chemical shifts of the C17 (176.15 p.p.m.) and C21 (167.45 p.p.m.) C atoms were confirmed by the presence of unambiguous cross peaks in the gHMBC spectrum linking (i) the 176.15 p.p.m. resonance with the H18 and H16 resonances and (ii) the 167.45 p.p.m. resonance with the H20 and H22 resonances. The ¹³C chemical shift of C20 (108.62 p.p.m.) was confirmed by direct correlation of the C20 and H20 resonances in the gHSQC matrix. The ¹³C chemical shifts of the C17, C21 and C20 atoms can be compared with those previously observed for ¹³C nuclei in the isolated D-ring analogue methyl 2-methylenecyclopentane acetate (Molander & Harris, 1997), i.e. 169.51, 167.31 and 111.18 p.p.m., respectively.

S2. Experimental

A solution of sodium ethoxide (1.243 M, 5 ml) was added slowly to a stirred solution of dehydroisoandrosterone (600 mg, 2 mmol) and triethyl phosphonoacetate (1.6 ml, 6 mmol) in ethanol (5 ml) at room temperature, under an N₂ atmosphere. The reaction mixture was refluxed for 20 h, then cooled to room temperature and concentrated in vacuo. The residue was diluted with water and the resulting suspension acidified (acetic acid) and extracted with a mixture of ethyl acetate and tetrahydrofuran (3:1, 60 ml). The organic layer was washed with water and brine, dried (Na₂SO₄) and the solvent removed by evaporation at reduced pressure. Crystallization of the residue from methanol gave the product ethyl 3β-hydroxypregna-5,17 (20)-dien-21-oate (525 mg, 70%) as fine colourless crystals, suitable for X-ray crystallographic analysis [m.p.: 457–9 K; literature 457–458 K (Wicha et al., 1977)]. ¹H NMR (400 MHz, CDCl₃, 298 K): δ 5.51 (1H, dd, J = 2.5, 2.5 Hz, H2O), 5.32 (1H, m, H6), 4.11 (2H, m, CH2, H22), 3.49 (1H, dddd, J = 4, 5, 11, 11 Hz, H3), 2.88–2.72 (2H, m, H16a,b), 2.31–2.15 (2H, m, H4a,b), 2.03 (1H, m, H7a), 1.85–1.72 (4H, br m, H12a, H15a, H1a, H2a), 1.68–1.41 (5H, br m, H11a,b, H8, H2b, H7b), 1.38–1.20 (2H, br m, H15b, H12b), 1.22 (3H, dd, CH₃, H23), 1.10–0.91 (3H, m, H1b, H14, H9), 0.99 (3H, s, CH₃, H19), 0.80 (3H, s, CH₃, H18); ¹³C{¹H} NMR (100 MHz, CDCl₃, 298 K): δ 176.15 (C17), 167.45 (C═O, C21), 140.82 (C5), 121.28 (C6), 108.62 (C20), 71.61 (C3), 59.50 (C22), 53.81 (C14), 50.21 (C9), 46.03 (C13), 42.20 (C4), 37.20 (C1), 36.56 (C10), 35.18 (C12), 31.64–31.55 (C7, C2, C8), 30.41 (C16), 24.45 (C15), 20.94 (C11), 19.39 (C19), 18.23 (C18), 14.36 (C23). ESMS (m/z): +ve ion, 381.15 [M + Na]⁺, 359.13, [M + H] ⁺.

S3. Refinement

C-bound H atoms were constrained as riding atoms, with C—H = 0.94–0.96 Å, and with U_iso(H)= 1.2U_eq(parent atom). The hydroxy H atom was located in a difference Fourier synthesis and constrained as a riding atom, with O—H = 0.91 Å. In the absence of significant anomalous scattering effects, Friedel pairs were merged. The absolute configuration is assigned on the basis of the known configuration of the starting material.

Computing details

Data collection: MSC/AFC7 Diffractometer Control Software for Windows (Molecular Structure Corporation, 1999); cell refinement: MSC/AFC7 Diffractometer Control Software for Windows; data reduction: TEXSAN for Windows (Molecular Structure Corporation, 2001); program(s) used to solve structure: TEXSAN for Windows; program(s) used to refine structure: TEXSAN for Windows and SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: TEXSAN for Windows and PLATON (Spek, 2003).

Figures

Fig. 1. Representative view of (II), with the atom-numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 30% probability level.

Ethyl 3β-hydroxypregna-5,17 (20)-dien-21-oate

Crystal data

C23H34O3	Z = 1
Mr = 358.50	F(000) = 196
Triclinic, P1	Dx = 1.187 Mg m^−3
Hall symbol: P 1	Mo Kα radiation, λ = 0.7107 Å
a = 6.3179 (17) Å	Cell parameters from 25 reflections
b = 8.0901 (16) Å	θ = 12.7–17.3°
c = 10.880 (2) Å	µ = 0.08 mm^−1
α = 73.8 (2)°	T = 295 K
β = 100.311 (19)°	Prism, colourless
γ = 109.285 (16)°	0.40 × 0.35 × 0.20 mm
V = 501.7 (5) Å^3

Data collection

Rigaku AFC-7R diffractometer	Rint = 0.033
Radiation source: Rigaku rotating anode	θmax = 25.0°, θmin = 2.8°
Graphite monochromator	h = −7→7
ω–2θ scans	k = 0→9
2086 measured reflections	l = −11→12
1756 independent reflections	3 standard reflections every 150 reflections
1506 reflections with I > 2σ(I)	intensity decay: 1.2%

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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.111	H-atom parameters constrained
S = 1.04	w = 1/[σ^2(Fo^2) + (0.0611P)^2 + 0.0627P] where P = (Fo^2 + 2Fc^2)/3
1756 reflections	(Δ/σ)max = 0.023
235 parameters	Δρmax = 0.15 e Å^−3
3 restraints	Δρmin = −0.19 e Å^−3

Special details

Experimental. The scan width was (1.73 + 0.30tanθ)° with an ω scan speed of 16° per minute (up to 4 scans to achieve I/σ(I) > 10). Stationary background counts were recorded at each end of the scan, and the scan time:background time ratio was 2:1.

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

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 > 2σ(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	1.0849 (4)	0.9636 (3)	1.1570 (2)	0.0604 (9)
O21	−0.0540 (5)	0.2129 (3)	0.2577 (3)	0.0655 (9)
O22	−0.2529 (4)	0.4108 (3)	0.1955 (2)	0.0536 (8)
C1	0.6876 (5)	0.9347 (4)	0.8535 (3)	0.0473 (10)
C2	0.8309 (7)	1.0190 (5)	0.9610 (4)	0.0543 (11)
C3	0.9404 (6)	0.8873 (4)	1.0563 (3)	0.0476 (10)
C4	1.0809 (6)	0.8287 (4)	0.9877 (3)	0.0477 (10)
C5	0.9449 (5)	0.7482 (4)	0.8786 (3)	0.0413 (9)
C6	0.9428 (6)	0.5873 (5)	0.8702 (3)	0.0492 (11)
C7	0.8129 (6)	0.4944 (5)	0.7670 (3)	0.0517 (11)
C8	0.7240 (5)	0.6185 (4)	0.6518 (3)	0.0407 (9)
C9	0.6315 (5)	0.7437 (4)	0.6964 (3)	0.0380 (9)
C10	0.8103 (5)	0.8621 (4)	0.7802 (3)	0.0390 (9)
C11	0.5107 (6)	0.8535 (4)	0.5832 (3)	0.0477 (11)
C12	0.3327 (5)	0.7395 (4)	0.5006 (3)	0.0461 (10)
C13	0.4329 (5)	0.6232 (4)	0.4540 (3)	0.0388 (9)
C14	0.5359 (5)	0.5092 (4)	0.5720 (3)	0.0393 (9)
C15	0.5749 (6)	0.3668 (5)	0.5194 (3)	0.0490 (11)
C16	0.3638 (6)	0.3179 (4)	0.4260 (3)	0.0476 (10)
C17	0.2711 (5)	0.4778 (4)	0.3912 (3)	0.0403 (10)
C18	0.6053 (6)	0.7415 (5)	0.3549 (3)	0.0529 (11)
C19	0.9796 (6)	1.0199 (5)	0.6967 (4)	0.0552 (11)
C20	0.0809 (5)	0.4933 (4)	0.3200 (3)	0.0451 (10)
C21	−0.0754 (5)	0.3561 (5)	0.2572 (3)	0.0465 (10)
C22	−0.4185 (6)	0.2935 (5)	0.1228 (4)	0.0600 (12)
C23	−0.5828 (6)	0.3922 (5)	0.0518 (4)	0.0636 (12)
H3	1.02330	1.03750	1.17800	0.0680*
H6	1.03110	0.52540	0.93550	0.0580*
H8	0.84270	0.68880	0.60100	0.0490*
H9	0.51800	0.66630	0.75150	0.0450*
H11	0.56550	0.83720	0.89060	0.0560*
H12	0.63010	1.02350	0.79400	0.0560*
H14	0.41730	0.44590	0.62690	0.0460*
H20	0.04360	0.60120	0.31020	0.0540*
H21	0.94470	1.12310	0.92560	0.0640*
H22	0.73810	1.05070	1.00490	0.0640*
H31	0.82550	0.78360	1.09440	0.0570*
H41	1.19990	0.93000	0.95550	0.0570*
H42	1.14020	0.74060	1.04860	0.0570*
H71	0.68710	0.39880	0.80360	0.0620*
H72	0.90680	0.44530	0.73960	0.0620*
H111	0.43870	0.91470	0.61760	0.0560*
H112	0.62000	0.93790	0.52990	0.0560*
H121	0.21180	0.66350	0.55130	0.0550*
H122	0.27690	0.81660	0.42930	0.0550*
H151	0.70730	0.41410	0.47690	0.0580*
H152	0.58600	0.26460	0.58760	0.0580*
H161	0.40180	0.29920	0.35190	0.0560*
H162	0.25560	0.21090	0.46690	0.0560*
H181	0.69840	0.84430	0.38560	0.0630*
H182	0.52650	0.77950	0.27510	0.0630*
H183	0.69540	0.67360	0.34590	0.0630*
H191	1.08670	1.08810	0.75170	0.0670*
H192	0.90120	1.09440	0.63730	0.0670*
H193	1.05470	0.97300	0.65340	0.0670*
H221	−0.49310	0.18340	0.17920	0.0720*
H222	−0.34690	0.26680	0.06410	0.0720*
H231	−0.68030	0.32940	−0.00790	0.0740*
H232	−0.50390	0.50950	0.00990	0.0740*
H233	−0.67130	0.39910	0.11270	0.0740*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O3	0.0694 (17)	0.0574 (15)	0.0578 (15)	0.0215 (13)	−0.0096 (12)	−0.0256 (12)
O21	0.0603 (15)	0.0517 (14)	0.0918 (19)	0.0223 (12)	−0.0096 (14)	−0.0320 (14)
O22	0.0453 (12)	0.0567 (14)	0.0646 (15)	0.0168 (11)	−0.0063 (11)	−0.0289 (12)
C1	0.0460 (17)	0.0456 (18)	0.0565 (19)	0.0218 (15)	−0.0024 (14)	−0.0167 (15)
C2	0.061 (2)	0.0469 (19)	0.061 (2)	0.0210 (16)	−0.0036 (17)	−0.0220 (16)
C3	0.0504 (18)	0.0421 (17)	0.0492 (18)	0.0090 (14)	0.0013 (14)	−0.0170 (14)
C4	0.0463 (17)	0.0469 (18)	0.0483 (18)	0.0170 (14)	−0.0020 (14)	−0.0091 (15)
C5	0.0375 (15)	0.0445 (17)	0.0418 (16)	0.0152 (13)	0.0052 (12)	−0.0055 (14)
C6	0.0539 (19)	0.0530 (19)	0.0458 (17)	0.0297 (15)	−0.0097 (14)	−0.0120 (14)
C7	0.065 (2)	0.0505 (19)	0.0487 (19)	0.0343 (17)	−0.0079 (16)	−0.0136 (15)
C8	0.0443 (17)	0.0385 (15)	0.0414 (16)	0.0179 (13)	0.0036 (13)	−0.0062 (13)
C9	0.0381 (15)	0.0366 (15)	0.0411 (16)	0.0151 (12)	0.0069 (12)	−0.0053 (13)
C10	0.0349 (15)	0.0361 (15)	0.0437 (16)	0.0118 (12)	0.0029 (12)	−0.0050 (12)
C11	0.0546 (19)	0.0416 (17)	0.0525 (19)	0.0265 (15)	−0.0079 (15)	−0.0135 (15)
C12	0.0440 (17)	0.0453 (17)	0.0524 (19)	0.0234 (14)	−0.0053 (14)	−0.0109 (15)
C13	0.0369 (15)	0.0367 (15)	0.0388 (16)	0.0113 (12)	0.0030 (13)	−0.0027 (13)
C14	0.0413 (16)	0.0376 (15)	0.0402 (16)	0.0180 (13)	0.0077 (13)	−0.0013 (13)
C15	0.0550 (19)	0.0446 (17)	0.0519 (19)	0.0242 (15)	0.0003 (16)	−0.0100 (15)
C16	0.0552 (19)	0.0414 (16)	0.0478 (18)	0.0180 (15)	0.0043 (15)	−0.0093 (14)
C17	0.0441 (17)	0.0376 (16)	0.0394 (17)	0.0130 (13)	0.0098 (13)	−0.0049 (13)
C18	0.0519 (19)	0.0521 (19)	0.0427 (17)	0.0075 (15)	0.0092 (14)	0.0012 (15)
C19	0.0463 (18)	0.0489 (19)	0.055 (2)	0.0030 (15)	0.0024 (15)	−0.0029 (16)
C20	0.0442 (17)	0.0393 (17)	0.0538 (19)	0.0154 (13)	0.0014 (14)	−0.0124 (14)
C21	0.0433 (17)	0.0486 (18)	0.0518 (19)	0.0147 (14)	0.0078 (14)	−0.0154 (15)
C22	0.052 (2)	0.062 (2)	0.067 (2)	0.0109 (17)	−0.0031 (17)	−0.0298 (19)
C23	0.048 (2)	0.061 (2)	0.067 (2)	0.0049 (17)	−0.0090 (17)	−0.0147 (18)

Geometric parameters (Å, º)

O3—C3	1.436 (4)	C2—H21	0.9400
O21—C21	1.208 (5)	C2—H22	0.9500
O22—C21	1.340 (4)	C3—H31	0.9600
O22—C22	1.445 (5)	C4—H41	0.9400
O3—H3	0.9100	C4—H42	0.9500
C1—C10	1.538 (5)	C6—H6	0.9500
C1—C2	1.520 (5)	C7—H71	0.9600
C2—C3	1.517 (5)	C7—H72	0.9400
C3—C4	1.511 (5)	C8—H8	0.9400
C4—C5	1.506 (5)	C9—H9	0.9600
C5—C6	1.326 (5)	C11—H111	0.9500
C5—C10	1.536 (5)	C11—H112	0.9400
C6—C7	1.494 (5)	C12—H121	0.9600
C7—C8	1.521 (5)	C12—H122	0.9400
C8—C9	1.539 (5)	C14—H14	0.9600
C8—C14	1.521 (5)	C15—H151	0.9400
C9—C11	1.546 (5)	C15—H152	0.9600
C9—C10	1.558 (5)	C16—H161	0.9400
C10—C19	1.549 (5)	C16—H162	0.9600
C11—C12	1.529 (5)	C18—H181	0.9500
C12—C13	1.522 (5)	C18—H182	0.9500
C13—C14	1.536 (5)	C18—H183	0.9400
C13—C17	1.517 (5)	C19—H191	0.9600
C13—C18	1.556 (5)	C19—H192	0.9400
C14—C15	1.524 (5)	C19—H193	0.9400
C15—C16	1.536 (5)	C20—H20	0.9500
C16—C17	1.519 (5)	C22—H221	0.9600
C17—C20	1.331 (5)	C22—H222	0.9500
C20—C21	1.460 (5)	C23—H231	0.9500
C22—C23	1.493 (6)	C23—H232	0.9400
C1—H11	0.9600	C23—H233	0.9600
C1—H12	0.9500
O3···O21^i	2.964 (4)	H20···O3^vi	2.8900
O3···C22^ii	3.382 (5)	H20···C12	2.7300
O3···C23^ii	3.403 (5)	H20···H122	2.4000
O21···C16	2.949 (5)	H20···H183^vii	2.5700
O21···O3^iii	2.964 (4)	H21···C19	2.9000
O3···H221^ii	2.6800	H21···H41	2.5200
O3···H20^iv	2.8900	H21···H191	2.3500
O21···H3^iii	2.0700	H21···H231^ii	2.5200
O21···H161	2.8000	H22···H3	2.3700
O21···H162	2.7200	H22···H222^i	2.2700
O21···H221	2.7000	H31···O22^iv	2.8100
O21···H222	2.5800	H31···H11	2.5400
O21···H233^v	2.8700	H41···C19	2.9200
O22···H31^vi	2.8100	H41···H21	2.5200
O22···H161^vii	2.7600	H41···H191	2.3500
C16···O21	2.949 (5)	H42···C20^iv	3.0800
C22···O3^viii	3.382 (5)	H42···H6	2.2600
C23···O3^viii	3.403 (5)	H71···H14	2.3700
C1···H111	2.7800	H72···C15	2.9500
C2···H191	2.8500	H111···C1	2.7800
C4···H191	2.8200	H111···H12	2.3100
C6···H9	2.9500	H112···C18	2.7700
C7···H152	2.9300	H112···C19	2.6600
C8···H193	2.9400	H112···H181	2.1100
C8···H181	2.9700	H112···H192	2.1700
C11···H181	2.6600	H121···C20	3.0600
C11···H12	2.8600	H121···H8^vii	2.5700
C11···H14	3.0600	H121···H14	2.4000
C11···H192	2.6800	H122···C20	2.9800
C12···H20	2.7300	H122···H20	2.4000
C15···H183	2.6400	H151···C18	2.8400
C15···H72	2.9500	H151···C20^v	2.9500
C16···H183	2.9500	H151···H183	2.2000
C18···H151	2.8400	H152···C7	2.9300
C18···H112	2.7700	H152···H12^xiii	2.5700
C18···H8	2.8200	H161···O21	2.8000
C19···H41	2.9200	H161···O22^v	2.7600
C19···H8	2.9500	H161···C22^v	2.9400
C19···H21	2.9000	H161···H221^v	2.5900
C19···H162^ix	3.0500	H161···H233^v	2.5100
C19···H112	2.6600	H162···O21	2.7200
C20···H122	2.9800	H162···C19^xiv	3.0500
C20···H42^vi	3.0800	H162···C21	3.0600
C20···H182	3.0100	H162···H193^xiv	2.5600
C20···H121	3.0600	H181···C8	2.9700
C20···H151^vii	2.9500	H181···C11	2.6600
C21···H162	3.0600	H181···H8	2.5000
C22···H161^vii	2.9400	H181···H112	2.1100
C23···H6^x	2.9300	H182···C20	3.0100
H3···O21^i	2.0700	H183···C15	2.6400
H3···H22	2.3700	H183···C16	2.9500
H6···C23^xi	2.9300	H183···H20^v	2.5700
H6···H42	2.2600	H183···H151	2.2000
H8···C18	2.8200	H191···C2	2.8500
H8···C19	2.9500	H191···C4	2.8200
H8···H121^v	2.5700	H191···H21	2.3500
H8···H181	2.5000	H191···H41	2.3500
H8···H193	2.4100	H192···C11	2.6800
H9···C6	2.9500	H192···H12	2.4500
H9···H11	2.2400	H192···H112	2.1700
H9···H14	2.3900	H193···C8	2.9400
H11···H9	2.2400	H193···H8	2.4100
H11···H31	2.5400	H193···H162^ix	2.5600
H11···H232^iv	2.5300	H221···O3^viii	2.6800
H12···C11	2.8600	H221···O21	2.7000
H12···H111	2.3100	H221···H161^vii	2.5900
H12···H152^xii	2.5700	H222···O21	2.5800
H12···H192	2.4500	H222···H22^iii	2.2700
H14···C11	3.0600	H231···H21^viii	2.5200
H14···H9	2.3900	H232···H11^vi	2.5300
H14···H71	2.3700	H233···O21^vii	2.8700
H14···H121	2.4000	H233···H161^vii	2.5100
C21—O22—C22	117.1 (3)	H41—C4—H42	110.00
C3—O3—H3	109.00	C5—C6—H6	117.00
C2—C1—C10	115.5 (4)	C7—C6—H6	117.00
C1—C2—C3	110.6 (4)	C6—C7—H71	108.00
O3—C3—C2	112.6 (3)	C6—C7—H72	109.00
C2—C3—C4	109.9 (3)	C8—C7—H71	109.00
O3—C3—C4	107.8 (4)	C8—C7—H72	109.00
C3—C4—C5	112.1 (4)	H71—C7—H72	109.00
C4—C5—C10	116.3 (3)	C7—C8—H8	109.00
C6—C5—C10	122.8 (4)	C9—C8—H8	109.00
C4—C5—C6	120.9 (4)	C14—C8—H8	109.00
C5—C6—C7	125.4 (4)	C8—C9—H9	106.00
C6—C7—C8	113.3 (4)	C10—C9—H9	106.00
C7—C8—C9	110.5 (3)	C11—C9—H9	106.00
C7—C8—C14	110.5 (3)	C9—C11—H111	108.00
C9—C8—C14	108.6 (3)	C9—C11—H112	108.00
C8—C9—C11	111.8 (3)	C12—C11—H111	108.00
C10—C9—C11	113.3 (3)	C12—C11—H112	108.00
C8—C9—C10	113.2 (3)	H111—C11—H112	110.00
C1—C10—C5	108.5 (3)	C11—C12—H121	109.00
C1—C10—C9	108.7 (3)	C11—C12—H122	109.00
C5—C10—C9	110.2 (3)	C13—C12—H121	109.00
C5—C10—C19	107.7 (3)	C13—C12—H122	110.00
C1—C10—C19	110.4 (3)	H121—C12—H122	109.00
C9—C10—C19	111.4 (3)	C8—C14—H14	106.00
C9—C11—C12	114.1 (3)	C13—C14—H14	106.00
C11—C12—C13	110.7 (3)	C15—C14—H14	106.00
C12—C13—C14	108.2 (3)	C14—C15—H151	111.00
C12—C13—C18	110.8 (3)	C14—C15—H152	110.00
C14—C13—C17	101.1 (3)	C16—C15—H151	112.00
C12—C13—C17	117.5 (3)	C16—C15—H152	111.00
C17—C13—C18	106.0 (3)	H151—C15—H152	109.00
C14—C13—C18	113.1 (3)	C15—C16—H161	110.00
C8—C14—C15	120.6 (4)	C15—C16—H162	110.00
C13—C14—C15	103.7 (3)	C17—C16—H161	111.00
C8—C14—C13	114.4 (3)	C17—C16—H162	111.00
C14—C15—C16	103.1 (4)	H161—C16—H162	109.00
C15—C16—C17	105.6 (3)	C13—C18—H181	109.00
C13—C17—C16	108.2 (3)	C13—C18—H182	109.00
C16—C17—C20	127.9 (4)	C13—C18—H183	109.00
C13—C17—C20	124.0 (4)	H181—C18—H182	110.00
C17—C20—C21	124.8 (4)	H181—C18—H183	110.00
O21—C21—O22	123.0 (4)	H182—C18—H183	110.00
O22—C21—C20	110.2 (4)	C10—C19—H191	109.00
O21—C21—C20	126.8 (4)	C10—C19—H192	109.00
O22—C22—C23	106.9 (4)	C10—C19—H193	109.00
C2—C1—H11	108.00	H191—C19—H192	110.00
C2—C1—H12	108.00	H191—C19—H193	110.00
C10—C1—H11	108.00	H192—C19—H193	111.00
C10—C1—H12	108.00	C17—C20—H20	117.00
H11—C1—H12	109.00	C21—C20—H20	118.00
C1—C2—H21	109.00	O22—C22—H221	110.00
C1—C2—H22	109.00	O22—C22—H222	110.00
C3—C2—H21	109.00	C23—C22—H221	110.00
C3—C2—H22	109.00	C23—C22—H222	110.00
H21—C2—H22	110.00	H221—C22—H222	109.00
O3—C3—H31	109.00	C22—C23—H231	110.00
C2—C3—H31	109.00	C22—C23—H232	109.00
C4—C3—H31	109.00	C22—C23—H233	109.00
C3—C4—H41	108.00	H231—C23—H232	111.00
C3—C4—H42	108.00	H231—C23—H233	109.00
C5—C4—H41	109.00	H232—C23—H233	109.00
C5—C4—H42	109.00
C22—O22—C21—O21	−2.6 (5)	C8—C9—C10—C1	−162.4 (3)
C22—O22—C21—C20	177.0 (3)	C10—C9—C11—C12	−179.4 (3)
C21—O22—C22—C23	−173.6 (4)	C8—C9—C11—C12	51.3 (4)
C2—C1—C10—C19	−70.2 (4)	C11—C9—C10—C1	69.0 (4)
C2—C1—C10—C9	167.4 (3)	C11—C9—C10—C5	−172.3 (3)
C10—C1—C2—C3	−55.5 (5)	C8—C9—C10—C19	75.9 (4)
C2—C1—C10—C5	47.6 (4)	C11—C9—C10—C19	−52.8 (4)
C1—C2—C3—O3	177.7 (4)	C9—C11—C12—C13	−53.7 (4)
C1—C2—C3—C4	57.5 (5)	C11—C12—C13—C17	169.3 (3)
C2—C3—C4—C5	−56.3 (4)	C11—C12—C13—C14	55.8 (4)
O3—C3—C4—C5	−179.3 (3)	C11—C12—C13—C18	−68.8 (4)
C3—C4—C5—C6	−127.2 (4)	C18—C13—C14—C8	62.4 (4)
C3—C4—C5—C10	52.4 (4)	C18—C13—C14—C15	−70.9 (4)
C4—C5—C10—C19	73.6 (4)	C12—C13—C14—C8	−60.8 (4)
C6—C5—C10—C1	133.7 (4)	C12—C13—C14—C15	165.9 (3)
C4—C5—C6—C7	179.5 (4)	C17—C13—C14—C8	175.2 (3)
C10—C5—C6—C7	−0.1 (6)	C17—C13—C14—C15	41.9 (4)
C4—C5—C10—C1	−45.9 (4)	C18—C13—C17—C20	−90.9 (4)
C4—C5—C10—C9	−164.8 (3)	C12—C13—C17—C20	33.5 (5)
C6—C5—C10—C9	14.8 (5)	C14—C13—C17—C16	−28.2 (4)
C6—C5—C10—C19	−106.8 (4)	C12—C13—C17—C16	−145.7 (3)
C5—C6—C7—C8	14.0 (6)	C18—C13—C17—C16	89.9 (4)
C6—C7—C8—C14	−161.9 (4)	C14—C13—C17—C20	151.0 (4)
C6—C7—C8—C9	−41.6 (5)	C13—C14—C15—C16	−39.9 (4)
C7—C8—C9—C11	−172.3 (3)	C8—C14—C15—C16	−169.6 (3)
C14—C8—C9—C10	179.7 (3)	C14—C15—C16—C17	21.9 (4)
C7—C8—C9—C10	58.3 (4)	C15—C16—C17—C13	4.3 (4)
C7—C8—C14—C13	179.3 (3)	C15—C16—C17—C20	−174.9 (4)
C7—C8—C14—C15	−56.0 (4)	C16—C17—C20—C21	−1.9 (6)
C14—C8—C9—C11	−50.9 (4)	C13—C17—C20—C21	179.1 (4)
C9—C8—C14—C15	−177.3 (3)	C17—C20—C21—O22	178.5 (4)
C9—C8—C14—C13	57.9 (4)	C17—C20—C21—O21	−1.8 (6)
C8—C9—C10—C5	−43.6 (4)

Symmetry codes: (i) x+1, y+1, z+1; (ii) x+2, y+1, z+1; (iii) x−1, y−1, z−1; (iv) x+1, y, z+1; (v) x+1, y, z; (vi) x−1, y, z−1; (vii) x−1, y, z; (viii) x−2, y−1, z−1; (ix) x+1, y+1, z; (x) x−2, y, z−1; (xi) x+2, y, z+1; (xii) x, y+1, z; (xiii) x, y−1, z; (xiv) x−1, y−1, z.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O21^i	0.91	2.07	2.964 (4)	167

Symmetry code: (i) x+1, y+1, z+1.