Triamcinolone acetonide acetate

Lu, X.; Tang, G.-P.; Gu, J.-M.; Hu, X.-R.

doi:10.1107/S1600536811000316

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 67| Part 2| February 2011| Page o360

doi:10.1107/S1600536811000316

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Triamcinolone acetonide acetate

Xiao Lu,^a Gu-Ping Tang,^a Jian-Ming Gu ^b and Xiu-Rong Hu ^b ^*

^aInstitute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, Zhejiang 310028, People's Republic of China, and ^bChemistry Department, Zhejiang University, Hangzhou, Zhejiang 310028, People's Republic of China
^*Correspondence e-mail: huxiurong@yahoo.com.cn

(Received 30 December 2010; accepted 5 January 2011; online 12 January 2011)

In the crystal structure of the title compound [systematic name: 2-(4b-fluoro-5-hydroxy-4a,6a,8,8-tetramethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-7,9-dioxapentaleno[2,1-a]phenanthren-6b-yl)-2-oxoethyl acetate], C₂₆H₃₃FO₇, the molecules are connected by intermolecular O—H⋯O hydrogen bonds into an infinite supramolecular chain along the b axis. The molecular framework consists of five condensed rings, including three six-membered rings and two five-membered rings. The cyclohexa-2,5-dienone ring is nearly planar [maximum deviation = 0.013 (3) Å], while the cyclohexane rings adopt chair conformations. The two five-membered rings, viz. cyclopentane and 1,3-dioxolane, display envelope conformations.

Related literature

For applications of triamcinolone acetonide in medicine, see: Barnes (1998 ); Buttgereit (2000 ); Uckermann et al. (2005 ). For the crystal structures of related triamcinolone acetonide acetates, see: Suitchlmezian et al. (2006 ); Jess & Näther (2006 ).

Experimental

Crystal data

C₂₆H₃₃FO₇
M_r = 476.52
Monoclinic, P 2₁
a = 7.5460 (7) Å
b = 14.8102 (4) Å
c = 11.5773 (3) Å
β = 109.905 (1)°
V = 1216.56 (12) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 296 K
0.38 × 0.33 × 0.26 mm

Data collection

Rigaku R-AXIS RAPID/ZJUG diffractometer
9347 measured reflections
2216 independent reflections
1866 reflections with I > 2σ(I)
R_int = 0.027

Refinement

R[F² > 2σ(F²)] = 0.035
wR(F²) = 0.100
S = 1.00
2216 reflections
308 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H201⋯O1ⁱ	0.82	1.98	2.793 (4)	169
Symmetry code: (i) $[-x+2, y-{\script{1\over 2}}, -z+2]$ .

Data collection: PROCESS-AUTO (Rigaku, 2006 ); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku, 2007 ); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811000316/xu5133sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811000316/xu5133Isup2.hkl

checkCIF report

Comment top

The glucocorticoid triamcinolone acetonide is clinically used for the treatment of suppression of inflammation in chronic inflammatory diseases such as asthma, rheumatiod arthritis, inflammatory bowel disease and autoimmune diseases (Barnes, 1998; Buttgereit, 2000; Uckermann et al., 2005). Triamcinolone acetonide acetate is another derivatives of triamcinolone, which has been used in therapy for several decades. Despite its great importance, no crystal structures of the title compound has been reported. But crystal structure of it's analogue compounds, triamcinolone diacetate chloroform solvate and triamcinole acetonide methanol solvate have been reported (Suitchlmezian et al., 2006 & Jess et al., 2006). In the title compound, the bond lengths and angles are in agreement with those reported for other triamcinolone derivatives (Suitchlmezian et al., 2006; Jess et al., 2006). and are within the expected ranges. The molecular framework consists of five condensed rings, including three six-membered rings and two five-membered rings. Atom O1 is coplanar with cyclohexa-1,4-diene ring (C8—C9—C10—C11—C12—C13), which is planar. Two central six-membered rings (C5—C6—C7—C8—C13—C14) and (C4—C5—C14—C15—C16—C17) are in chair conformation. Two five-membered rings display twisted envelope conformations. The respective r.m.s. deviations for four atoms C1/C2/C3/C17 and C1/C2/O6/O7 are 0.0359 Å, 0.0225Å respectively. The fifth atoms C4, C22 deviate from the above planes by 0.688 (4) Å, 0.458 (4)Å respectively. Hydroxy group and one of the carboxyl O atom are involved in the hydrogen- bonded network. Atom O2 from hydroxy group in the molecule at (x,y,z) act as hydrogen bond donor, to O1 atom of carboxyl group in the molecule (2 - x,-1/2 + y,2 - z). Crystal packing is influenced by this intermolecular hydrogen bond interaction that links the molecules into a chain propagating along b axis.

Related literature top

For applications of triamcinolone acetonide in medicine, see: Barnes (1998); Buttgereit (2000); Uckermann et al. (2005). For the crystal structures of related triamcinolone acetonide acetates, see: Suitchlmezian et al. (2006); Jess & Näther (2006).

Experimental top

The crude product of the title compound was supplied by Zhejiang Xianju Pharmaceutical Co., LTD. It was recrystallized from methanol solution, giving single crystals suitable for X-ray diffraction.

Computing details top

Data collection: PROCESS-AUTO (Rigaku, 2006); cell refinement: PROCESS-AUTO (Rigaku, 2006); data reduction: CrystalStructure (Rigaku, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. Molecular structure of the title compound (I) showing atom-labelling scheme and displacement ellipsoids at 50% probability level. H atoms are shown as small circles of arbitrary radii.
	Fig. 2. A chain of molecules linked through hydrogen-bonded interactions propagating along b axis. Hydrogen bonds are shown as dashed lines. [Symmetric code: (i)(2 - x,-1/2 + y,2 - z); (ii)(2 - x,1/2 + y,2 - z)]

2-(4b-Fluoro-5-hydroxy-4a,6a,8,8-tetramethyl-2-oxo- 2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-7,9-dioxa- pentaleno[2,1-a]phenanthren-6b-yl)-2-oxoethyl acetate top

Crystal data top

C₂₆H₃₃FO₇	F(000) = 508
M_r = 476.52	D_x = 1.301 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 8589 reflections
a = 7.5460 (7) Å	θ = 3.2–27.4°
b = 14.8102 (4) Å	µ = 0.10 mm⁻¹
c = 11.5773 (3) Å	T = 296 K
β = 109.905 (1)°	Chunk, colorless
V = 1216.56 (12) Å³	0.38 × 0.33 × 0.26 mm
Z = 2

Data collection top

Rigaku R-AXIS RAPID/ZJUG diffractometer	1866 reflections with I > 2σ(I)
Radiation source: rolling anode	R_int = 0.027
Graphite monochromator	θ_max = 25.0°, θ_min = 3.2°
Detector resolution: 10.00 pixels mm^-1	h = −8→8
ω scans	k = −17→17
9347 measured reflections	l = −13→13
2216 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.100	H-atom parameters constrained
S = 1.00	w = 1/[σ²(F_o²) + (0.0428P)² + 0.6583P] where P = (F_o² + 2F_c²)/3
2216 reflections	(Δ/σ)_max < 0.001
308 parameters	Δρ_max = 0.18 e Å⁻³
1 restraint	Δρ_min = −0.21 e Å⁻³

Crystal data top

C₂₆H₃₃FO₇	V = 1216.56 (12) Å³
M_r = 476.52	Z = 2
Monoclinic, P2₁	Mo Kα radiation
a = 7.5460 (7) Å	µ = 0.10 mm⁻¹
b = 14.8102 (4) Å	T = 296 K
c = 11.5773 (3) Å	0.38 × 0.33 × 0.26 mm
β = 109.905 (1)°

Data collection top

Rigaku R-AXIS RAPID/ZJUG diffractometer	1866 reflections with I > 2σ(I)
9347 measured reflections	R_int = 0.027
2216 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.035	1 restraint
wR(F²) = 0.100	H-atom parameters constrained
S = 1.00	Δρ_max = 0.18 e Å⁻³
2216 reflections	Δρ_min = −0.21 e Å⁻³
308 parameters

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
F1	0.6313 (3)	0.54106 (13)	0.76554 (17)	0.0388 (5)
O6	0.5255 (4)	0.35878 (18)	0.4342 (2)	0.0425 (6)
O7	0.2113 (4)	0.3480 (2)	0.3882 (2)	0.0580 (8)
O2	0.9010 (4)	0.3514 (2)	0.9117 (2)	0.0498 (7)
H201	0.9978	0.3303	0.9056	0.075*
O1	0.7606 (4)	0.76945 (19)	1.0779 (3)	0.0558 (8)
O4	0.8680 (4)	0.1362 (2)	0.4470 (3)	0.0638 (9)
O3	0.5322 (4)	0.1277 (2)	0.4898 (3)	0.0582 (8)
O5	0.9888 (5)	0.1500 (2)	0.6510 (3)	0.0728 (9)
C8	0.5342 (5)	0.5590 (3)	0.9699 (3)	0.0407 (9)
C14	0.6558 (5)	0.4623 (2)	0.8393 (3)	0.0322 (7)
C16	0.7704 (5)	0.3720 (3)	0.6873 (3)	0.0376 (8)
H16A	0.7556	0.4198	0.6275	0.045*
H16B	0.8731	0.3336	0.6848	0.045*
C5	0.4670 (5)	0.4121 (2)	0.7923 (3)	0.0336 (8)
H5	0.4738	0.3602	0.8461	0.040*
C7	0.3424 (5)	0.5160 (3)	0.9231 (4)	0.0480 (10)
H7A	0.2468	0.5613	0.9171	0.058*
H7B	0.3334	0.4700	0.9805	0.058*
C13	0.6966 (5)	0.4988 (2)	0.9729 (3)	0.0361 (8)
C17	0.5885 (5)	0.3160 (2)	0.6510 (3)	0.0333 (8)
C9	0.5589 (5)	0.6453 (3)	1.0052 (3)	0.0433 (9)
H9	0.4539	0.6789	1.0033	0.052*
C6	0.3070 (5)	0.4733 (3)	0.7971 (4)	0.0425 (9)
H6A	0.1915	0.4384	0.7748	0.051*
H6B	0.2891	0.5210	0.7367	0.051*
C4	0.4318 (4)	0.3771 (3)	0.6626 (3)	0.0339 (8)
H4	0.4259	0.4300	0.6104	0.041*
C10	0.7421 (5)	0.6892 (3)	1.0465 (3)	0.0424 (9)
C11	0.9034 (5)	0.6337 (3)	1.0487 (4)	0.0479 (10)
H11	1.0234	0.6590	1.0748	0.058*
C3	0.2545 (5)	0.3219 (3)	0.6011 (4)	0.0450 (9)
H3A	0.1427	0.3595	0.5788	0.054*
H3B	0.2417	0.2735	0.6542	0.054*
C15	0.8226 (5)	0.4144 (3)	0.8163 (3)	0.0368 (8)
H15	0.9191	0.4603	0.8229	0.044*
C12	0.8813 (5)	0.5480 (3)	1.0142 (3)	0.0432 (9)
H12	0.9880	0.5160	1.0156	0.052*
C26	0.6145 (5)	0.2300 (3)	0.7297 (3)	0.0430 (9)
H26A	0.7140	0.1940	0.7194	0.065*
H26B	0.4995	0.1959	0.7042	0.065*
H26C	0.6464	0.2464	0.8146	0.065*
C19	0.7634 (7)	0.2173 (3)	0.4445 (4)	0.0599 (11)
H19A	0.7220	0.2420	0.3620	0.072*
H19B	0.8453	0.2614	0.4989	0.072*
C1	0.5043 (6)	0.2880 (3)	0.5130 (3)	0.0386 (8)
C2	0.2878 (5)	0.2844 (3)	0.4866 (3)	0.0447 (9)
H2	0.2359	0.2235	0.4651	0.054*
C22	0.3498 (6)	0.3674 (3)	0.3347 (3)	0.0502 (10)
C18	0.5929 (6)	0.2019 (3)	0.4831 (3)	0.0438 (9)
C25	0.7128 (7)	0.4231 (3)	1.0695 (4)	0.0530 (10)
H25A	0.5968	0.3898	1.0471	0.080*
H25B	0.7376	0.4499	1.1490	0.080*
H25C	0.8140	0.3830	1.0720	0.080*
C24	0.3353 (8)	0.3027 (4)	0.2306 (4)	0.0689 (14)
H24A	0.4307	0.3168	0.1959	0.103*
H24B	0.2132	0.3081	0.1685	0.103*
H24C	0.3527	0.2419	0.2616	0.103*
C20	0.9797 (6)	0.1098 (3)	0.5594 (4)	0.0568 (11)
C23	0.3293 (8)	0.4648 (4)	0.2940 (4)	0.0709 (14)
H23A	0.4223	0.4789	0.2572	0.106*
H23B	0.3469	0.5032	0.3639	0.106*
H23C	0.2057	0.4743	0.2352	0.106*
C21	1.0917 (8)	0.0281 (4)	0.5528 (6)	0.0910 (18)
H21A	1.0576	0.0087	0.4689	0.137*
H21B	1.0658	−0.0194	0.6012	0.137*
H21C	1.2235	0.0425	0.5840	0.137*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0395 (11)	0.0373 (12)	0.0392 (11)	−0.0020 (9)	0.0130 (9)	0.0066 (9)
O6	0.0465 (14)	0.0450 (16)	0.0341 (12)	−0.0009 (12)	0.0114 (11)	0.0025 (12)
O7	0.0448 (15)	0.077 (2)	0.0448 (14)	0.0049 (15)	0.0062 (12)	0.0030 (15)
O2	0.0450 (15)	0.0604 (19)	0.0387 (13)	0.0179 (14)	0.0076 (12)	0.0010 (13)
O1	0.0597 (18)	0.0436 (18)	0.0664 (19)	−0.0124 (14)	0.0245 (15)	−0.0184 (15)
O4	0.0615 (18)	0.068 (2)	0.0601 (18)	0.0153 (16)	0.0186 (15)	−0.0178 (16)
O3	0.069 (2)	0.0429 (18)	0.0593 (17)	−0.0048 (15)	0.0181 (15)	−0.0110 (14)
O5	0.082 (2)	0.075 (2)	0.0631 (19)	−0.0134 (19)	0.0274 (17)	−0.0146 (19)
C8	0.039 (2)	0.046 (2)	0.043 (2)	−0.0073 (17)	0.0224 (16)	−0.0088 (18)
C14	0.0344 (18)	0.0307 (18)	0.0322 (16)	0.0007 (15)	0.0123 (14)	0.0025 (15)
C16	0.0355 (18)	0.045 (2)	0.0375 (18)	−0.0023 (17)	0.0195 (15)	−0.0066 (17)
C5	0.0340 (17)	0.0343 (19)	0.0372 (17)	−0.0021 (15)	0.0183 (15)	−0.0010 (15)
C7	0.039 (2)	0.054 (3)	0.062 (2)	−0.0047 (19)	0.032 (2)	−0.013 (2)
C13	0.0371 (19)	0.038 (2)	0.0347 (18)	−0.0003 (16)	0.0142 (16)	−0.0025 (15)
C17	0.0349 (18)	0.0345 (19)	0.0324 (16)	−0.0015 (15)	0.0140 (15)	−0.0026 (15)
C9	0.0369 (19)	0.047 (2)	0.048 (2)	−0.0009 (17)	0.0170 (17)	−0.0122 (18)
C6	0.0271 (17)	0.050 (2)	0.053 (2)	−0.0051 (16)	0.0169 (16)	−0.0100 (19)
C4	0.0316 (17)	0.0364 (19)	0.0345 (17)	−0.0037 (15)	0.0122 (15)	−0.0007 (15)
C10	0.042 (2)	0.048 (3)	0.0382 (19)	−0.0085 (18)	0.0159 (17)	−0.0087 (18)
C11	0.0365 (19)	0.057 (3)	0.049 (2)	−0.0062 (19)	0.0123 (17)	−0.013 (2)
C3	0.037 (2)	0.048 (2)	0.052 (2)	−0.0076 (17)	0.0171 (17)	−0.0077 (18)
C15	0.0343 (18)	0.038 (2)	0.0406 (19)	0.0000 (16)	0.0163 (15)	−0.0046 (16)
C12	0.0379 (19)	0.053 (3)	0.0385 (19)	−0.0013 (18)	0.0130 (16)	−0.0100 (19)
C26	0.046 (2)	0.042 (2)	0.0373 (19)	−0.0022 (18)	0.0098 (17)	−0.0018 (18)
C19	0.068 (3)	0.057 (3)	0.064 (3)	0.011 (2)	0.035 (2)	−0.004 (2)
C1	0.0438 (19)	0.038 (2)	0.0345 (18)	−0.0009 (17)	0.0139 (16)	−0.0025 (16)
C2	0.044 (2)	0.045 (2)	0.041 (2)	−0.0104 (18)	0.0103 (17)	−0.0103 (17)
C22	0.048 (2)	0.062 (3)	0.0328 (18)	0.006 (2)	0.0041 (17)	0.0013 (19)
C18	0.047 (2)	0.041 (2)	0.0375 (19)	0.0025 (18)	0.0079 (17)	−0.0035 (17)
C25	0.066 (3)	0.058 (3)	0.038 (2)	0.006 (2)	0.0218 (19)	0.0061 (19)
C24	0.079 (3)	0.075 (3)	0.045 (2)	−0.001 (3)	0.012 (2)	−0.011 (2)
C20	0.047 (2)	0.054 (3)	0.069 (3)	−0.008 (2)	0.018 (2)	−0.009 (2)
C23	0.084 (4)	0.060 (3)	0.055 (3)	0.011 (3)	0.004 (3)	0.009 (2)
C21	0.080 (4)	0.069 (4)	0.123 (5)	0.012 (3)	0.033 (4)	−0.008 (4)

Geometric parameters (Å, º) top

F1—C14	1.420 (4)	C6—H6B	0.9700
O6—C1	1.434 (4)	C4—C3	1.523 (5)
O6—C22	1.436 (4)	C4—H4	0.9800
O7—C22	1.414 (5)	C10—C11	1.462 (6)
O7—C2	1.439 (5)	C11—C12	1.325 (6)
O2—C15	1.412 (5)	C11—H11	0.9300
O2—H201	0.8200	C3—C2	1.535 (5)
O1—C10	1.237 (5)	C3—H3A	0.9700
O4—C20	1.346 (5)	C3—H3B	0.9700
O4—C19	1.431 (5)	C15—H15	0.9800
O3—C18	1.204 (5)	C12—H12	0.9300
O5—C20	1.197 (5)	C26—H26A	0.9600
C8—C9	1.335 (5)	C26—H26B	0.9600
C8—C7	1.503 (5)	C26—H26C	0.9600
C8—C13	1.506 (5)	C19—C18	1.516 (6)
C14—C5	1.533 (5)	C19—H19A	0.9700
C14—C15	1.545 (5)	C19—H19B	0.9700
C14—C13	1.567 (5)	C1—C18	1.533 (5)
C16—C17	1.535 (5)	C1—C2	1.557 (6)
C16—C15	1.542 (5)	C2—H2	0.9800
C16—H16A	0.9700	C22—C23	1.509 (7)
C16—H16B	0.9700	C22—C24	1.514 (6)
C5—C4	1.523 (5)	C25—H25A	0.9600
C5—C6	1.526 (5)	C25—H25B	0.9600
C5—H5	0.9800	C25—H25C	0.9600
C7—C6	1.528 (5)	C24—H24A	0.9600
C7—H7A	0.9700	C24—H24B	0.9600
C7—H7B	0.9700	C24—H24C	0.9600
C13—C12	1.499 (5)	C20—C21	1.493 (7)
C13—C25	1.559 (5)	C23—H23A	0.9600
C17—C4	1.531 (5)	C23—H23B	0.9600
C17—C26	1.539 (5)	C23—H23C	0.9600
C17—C1	1.561 (5)	C21—H21A	0.9600
C9—C10	1.453 (5)	C21—H21B	0.9600
C9—H9	0.9300	C21—H21C	0.9600
C6—H6A	0.9700

C1—O6—C22	107.6 (3)	O2—C15—C16	112.9 (3)
C22—O7—C2	108.9 (3)	O2—C15—C14	108.5 (3)
C15—O2—H201	109.5	C16—C15—C14	113.5 (3)
C20—O4—C19	115.0 (3)	O2—C15—H15	107.2
C9—C8—C7	122.2 (4)	C16—C15—H15	107.2
C9—C8—C13	122.1 (3)	C14—C15—H15	107.2
C7—C8—C13	115.7 (3)	C11—C12—C13	124.7 (4)
F1—C14—C5	105.6 (3)	C11—C12—H12	117.6
F1—C14—C15	102.7 (2)	C13—C12—H12	117.6
C5—C14—C15	115.4 (3)	C17—C26—H26A	109.5
F1—C14—C13	104.6 (3)	C17—C26—H26B	109.5
C5—C14—C13	111.4 (3)	H26A—C26—H26B	109.5
C15—C14—C13	115.5 (3)	C17—C26—H26C	109.5
C17—C16—C15	113.3 (3)	H26A—C26—H26C	109.5
C17—C16—H16A	108.9	H26B—C26—H26C	109.5
C15—C16—H16A	108.9	O4—C19—C18	112.7 (4)
C17—C16—H16B	108.9	O4—C19—H19A	109.1
C15—C16—H16B	108.9	C18—C19—H19A	109.1
H16A—C16—H16B	107.7	O4—C19—H19B	109.1
C4—C5—C6	111.3 (3)	C18—C19—H19B	109.1
C4—C5—C14	110.1 (2)	H19A—C19—H19B	107.8
C6—C5—C14	110.5 (3)	O6—C1—C18	108.2 (3)
C4—C5—H5	108.3	O6—C1—C2	103.8 (3)
C6—C5—H5	108.3	C18—C1—C2	115.9 (3)
C14—C5—H5	108.3	O6—C1—C17	111.3 (3)
C8—C7—C6	110.7 (3)	C18—C1—C17	113.3 (3)
C8—C7—H7A	109.5	C2—C1—C17	104.1 (3)
C6—C7—H7A	109.5	O7—C2—C3	107.9 (3)
C8—C7—H7B	109.5	O7—C2—C1	104.1 (3)
C6—C7—H7B	109.5	C3—C2—C1	106.7 (3)
H7A—C7—H7B	108.1	O7—C2—H2	112.5
C12—C13—C8	112.4 (3)	C3—C2—H2	112.5
C12—C13—C25	106.5 (3)	C1—C2—H2	112.5
C8—C13—C25	107.9 (3)	O7—C22—O6	104.4 (3)
C12—C13—C14	109.3 (3)	O7—C22—C23	108.6 (4)
C8—C13—C14	107.2 (3)	O6—C22—C23	107.7 (4)
C25—C13—C14	113.7 (3)	O7—C22—C24	110.8 (4)
C4—C17—C16	107.5 (3)	O6—C22—C24	112.2 (4)
C4—C17—C26	112.6 (3)	C23—C22—C24	112.7 (4)
C16—C17—C26	111.3 (3)	O3—C18—C19	122.4 (4)
C4—C17—C1	100.9 (3)	O3—C18—C1	122.7 (4)
C16—C17—C1	116.0 (3)	C19—C18—C1	114.9 (4)
C26—C17—C1	108.2 (3)	C13—C25—H25A	109.5
C8—C9—C10	123.2 (4)	C13—C25—H25B	109.5
C8—C9—H9	118.4	H25A—C25—H25B	109.5
C10—C9—H9	118.4	C13—C25—H25C	109.5
C5—C6—C7	113.4 (3)	H25A—C25—H25C	109.5
C5—C6—H6A	108.9	H25B—C25—H25C	109.5
C7—C6—H6A	108.9	C22—C24—H24A	109.5
C5—C6—H6B	108.9	C22—C24—H24B	109.5
C7—C6—H6B	108.9	H24A—C24—H24B	109.5
H6A—C6—H6B	107.7	C22—C24—H24C	109.5
C3—C4—C5	118.3 (3)	H24A—C24—H24C	109.5
C3—C4—C17	102.9 (3)	H24B—C24—H24C	109.5
C5—C4—C17	114.0 (3)	O5—C20—O4	122.7 (4)
C3—C4—H4	107.0	O5—C20—C21	125.8 (5)
C5—C4—H4	107.0	O4—C20—C21	111.4 (4)
C17—C4—H4	107.0	C22—C23—H23A	109.5
O1—C10—C9	121.8 (4)	C22—C23—H23B	109.5
O1—C10—C11	121.7 (4)	H23A—C23—H23B	109.5
C9—C10—C11	116.6 (3)	C22—C23—H23C	109.5
C12—C11—C10	121.0 (4)	H23A—C23—H23C	109.5
C12—C11—H11	119.5	H23B—C23—H23C	109.5
C10—C11—H11	119.5	C20—C21—H21A	109.5
C4—C3—C2	102.9 (3)	C20—C21—H21B	109.5
C4—C3—H3A	111.2	H21A—C21—H21B	109.5
C2—C3—H3A	111.2	C20—C21—H21C	109.5
C4—C3—H3B	111.2	H21A—C21—H21C	109.5
C2—C3—H3B	111.2	H21B—C21—H21C	109.5
H3A—C3—H3B	109.1

F1—C14—C5—C4	67.2 (3)	F1—C14—C15—O2	161.5 (3)
C15—C14—C5—C4	−45.5 (4)	C5—C14—C15—O2	−84.1 (3)
C13—C14—C5—C4	−179.8 (3)	C13—C14—C15—O2	48.3 (4)
F1—C14—C5—C6	−56.1 (3)	F1—C14—C15—C16	−72.2 (4)
C15—C14—C5—C6	−168.9 (3)	C5—C14—C15—C16	42.2 (4)
C13—C14—C5—C6	56.9 (4)	C13—C14—C15—C16	174.6 (3)
C9—C8—C7—C6	125.6 (4)	C10—C11—C12—C13	−1.3 (6)
C13—C8—C7—C6	−53.7 (5)	C8—C13—C12—C11	2.3 (5)
C9—C8—C13—C12	−2.4 (5)	C25—C13—C12—C11	−115.6 (4)
C7—C8—C13—C12	176.9 (3)	C14—C13—C12—C11	121.2 (4)
C9—C8—C13—C25	114.7 (4)	C20—O4—C19—C18	−77.7 (5)
C7—C8—C13—C25	−66.0 (4)	C22—O6—C1—C18	99.8 (3)
C9—C8—C13—C14	−122.5 (4)	C22—O6—C1—C2	−23.8 (4)
C7—C8—C13—C14	56.8 (4)	C22—O6—C1—C17	−135.2 (3)
F1—C14—C13—C12	−65.8 (3)	C4—C17—C1—O6	78.1 (3)
C5—C14—C13—C12	−179.5 (3)	C16—C17—C1—O6	−37.7 (4)
C15—C14—C13—C12	46.3 (4)	C26—C17—C1—O6	−163.5 (3)
F1—C14—C13—C8	56.3 (3)	C4—C17—C1—C18	−159.7 (3)
C5—C14—C13—C8	−57.4 (4)	C16—C17—C1—C18	84.5 (4)
C15—C14—C13—C8	168.4 (3)	C26—C17—C1—C18	−41.3 (4)
F1—C14—C13—C25	175.4 (3)	C4—C17—C1—C2	−33.0 (4)
C5—C14—C13—C25	61.8 (4)	C16—C17—C1—C2	−148.8 (3)
C15—C14—C13—C25	−72.5 (4)	C26—C17—C1—C2	85.4 (3)
C15—C16—C17—C4	55.6 (4)	C22—O7—C2—C3	129.1 (3)
C15—C16—C17—C26	−68.1 (4)	C22—O7—C2—C1	16.0 (4)
C15—C16—C17—C1	167.7 (3)	C4—C3—C2—O7	−90.1 (3)
C7—C8—C9—C10	−177.7 (4)	C4—C3—C2—C1	21.3 (4)
C13—C8—C9—C10	1.6 (6)	O6—C1—C2—O7	4.9 (4)
C4—C5—C6—C7	−175.6 (3)	C18—C1—C2—O7	−113.5 (3)
C14—C5—C6—C7	−52.9 (4)	C17—C1—C2—O7	121.5 (3)
C8—C7—C6—C5	50.0 (5)	O6—C1—C2—C3	−109.0 (3)
C6—C5—C4—C3	−59.5 (4)	C18—C1—C2—C3	132.6 (3)
C14—C5—C4—C3	177.6 (3)	C17—C1—C2—C3	7.5 (4)
C6—C5—C4—C17	179.4 (3)	C2—O7—C22—O6	−31.0 (4)
C14—C5—C4—C17	56.5 (4)	C2—O7—C22—C23	−145.7 (3)
C16—C17—C4—C3	169.2 (3)	C2—O7—C22—C24	90.0 (4)
C26—C17—C4—C3	−67.9 (4)	C1—O6—C22—O7	34.3 (4)
C1—C17—C4—C3	47.2 (3)	C1—O6—C22—C23	149.6 (3)
C16—C17—C4—C5	−61.5 (4)	C1—O6—C22—C24	−85.8 (4)
C26—C17—C4—C5	61.5 (4)	O4—C19—C18—O3	−14.4 (6)
C1—C17—C4—C5	176.6 (3)	O4—C19—C18—C1	165.5 (3)
C8—C9—C10—O1	179.5 (4)	O6—C1—C18—O3	−146.6 (4)
C8—C9—C10—C11	−0.4 (6)	C2—C1—C18—O3	−30.6 (5)
O1—C10—C11—C12	−179.7 (4)	C17—C1—C18—O3	89.6 (5)
C9—C10—C11—C12	0.2 (6)	O6—C1—C18—C19	33.5 (4)
C5—C4—C3—C2	−169.4 (3)	C2—C1—C18—C19	149.4 (3)
C17—C4—C3—C2	−42.8 (4)	C17—C1—C18—C19	−90.4 (4)
C17—C16—C15—O2	76.4 (4)	C19—O4—C20—O5	1.2 (6)
C17—C16—C15—C14	−47.6 (4)	C19—O4—C20—C21	−176.7 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H201···O1ⁱ	0.82	1.98	2.793 (4)	169

Symmetry code: (i) −x+2, y−1/2, −z+2.

Experimental details

Crystal data
Chemical formula	C₂₆H₃₃FO₇
M_r	476.52
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	296
a, b, c (Å)	7.5460 (7), 14.8102 (4), 11.5773 (3)
β (°)	109.905 (1)
V (Å³)	1216.56 (12)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.38 × 0.33 × 0.26

Data collection
Diffractometer	Rigaku R-AXIS RAPID/ZJUG diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	9347, 2216, 1866
R_int	0.027
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.035, 0.100, 1.00
No. of reflections	2216
No. of parameters	308
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.21

Computer programs: PROCESS-AUTO (Rigaku, 2006), CrystalStructure (Rigaku, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H201···O1ⁱ	0.82	1.98	2.793 (4)	169

Symmetry code: (i) −x+2, y−1/2, −z+2.

Acknowledgements

The project was supported by the Zhejiang Provincial Natural Science Foundation of China (J200801).

References

Barnes, P. J. (1998). Clin. Sci. 94, 557–572. Web of Science CAS PubMed Google Scholar
Buttgereit, F. (2000). Z. Rheumatol. 59, 119–123. CrossRef Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Jess, I. & Näther, C. (2006). Acta Cryst. E62, 0960–0962. Web of Science CSD CrossRef IUCr Journals Google Scholar
Rigaku (2006). PROCESS-AUTO. Rigaku Corporation, Tokyo, Japan. Google Scholar
Rigaku (2007). CrystalStructure. Rigaku Corporation, Tokyo, Japan. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Suitchlmezian, V., Jess, I. & Näther, C. (2006). Acta Cryst. E62, 0788–0790. Google Scholar
Uckermann, O., Kutzera, F., Wolf, A., Pannicke, T., Reichenbach, A., Wiedemann, P., Wolf, S. & Bringmann, A. (2005). J. Pharmacol. Exp. Ther. 315, 1036–1045. Web of Science CrossRef PubMed CAS Google Scholar