7-Acetyl-12-methoxy­horminone from Jamaican Hyptis verticillata (Labiatae)

The title compound, a horminone derivative with the systematic name 7-acetyl-12-methoxy­abieta-8,12-diene-11,14-dione, C₂₃H₃₂O₅, was isolated from Hyptis verticillata from St. Mary, Jamaica. In the mol­ecule, there are three fused six-membered rings, namely a substituted quinone ring in a slight boat conformation fused to a central acetyl- and methyl-substituted cyclo­hexene ring in a half-chair conformation, which is trans-fused to a dimethyl-substituted cyclo­hexane ring in a chair conformation. A single weak intra­molecular C—H...O hydrogen bond links mol­ecules into extended chains in the b axis direction.

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.040
• wR factor = 0.099
• Data-to-parameter ratio = 9.4

checkCIF/PLATON results

No syntax errors found



Alert level C
ABSTM02_ALERT_3_C  The ratio of expected to reported Tmax/Tmin(RR') is < 0.90
            Tmin and Tmax reported:      0.838     0.988
            Tmin(prime) and Tmax expected:      0.977     0.986
            RR(prime) =      0.856
            Please check that your absorption correction is appropriate.
PLAT061_ALERT_3_C Tmax/Tmin Range Test RR' too Large .............       0.86

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           27.49
           From the CIF: _reflns_number_total               2444
           Count of symmetry unique reflns         2456
           Completeness (_total/calc)             99.51%
           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
   2 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
   1 ALERT type 4 Improvement, methodology, query or suggestion


checkCIF publication errors

Alert level A
PUBL024_ALERT_1_A The number of authors is greater than 5.
              Please specify the role of each of the co-authors
              for your paper.

Author Response: 3. The authors; a. Duanne Biggs is my graduate student who isolated the compound from the plant he is working on. b. Mohammed Bakir is the local person hear who is knowledgable about x-rays and how to manulipate the programme and put the paper together. c. Willem Mulder is our theoretical chemist who did the calculations. d. William Reynolds allowed Duanne to visit his lab for three months to do some structural illusidation on his isolates. e. Alan Lough collected the data, solved and refined the structure and contributed to writng the paper and drew figures.

   1 ALERT level A = Data missing that is essential or data in wrong format
   0 ALERT level G = General alerts. Data that may be required is missing

---

S1. Comment

The Hyptis genus has approximately 400 species and is a member of the Labiatae family, which grows mostly in the tropical Americas. A number of these species possess significant biological activities, including teratogenic, antifertility, mycotoxinic and phytotoxinic properties (Delgado et al., 1985). Hyptis verticillata (Labiatae), known colloquially as 'John Charles', is widely used in folklore medicine as a treatment for itching, insect stings and rheumatoid arthritis (Porter & Reese, 1998). In Mexico, the plant is known as 'hierda martina' and the whole plant is boiled and rubbed for rheumatism and skin infection (Pereda-Miranda et al., 1993). The acetone and ethanol extracts of the roots of Hyptis verticillata have been found to have antimicrobial and cytotoxic activity (Gonzalez et al., 1994). While the aerial parts have been investigated for phytochemicals, the roots have not, to date. From a dichloromethane extract of the roots, the title horminone derivative, (I), which is a new natural product, has been isolated. The synthesis of 7-acetyl-12-methoxy horminone from 7-acetyl horminone has been reported previously (Ewards et al., 1962).

Compounds with structures closely related to that of (I) have been reported to show significant biological activity as tumour inhibitors (Jonathan et al., 1989) or as antifeedants (Kubo et al., 1984) and to possess antibacterial and antiviral activity (Batista et al., 1995). Although a variety of compounds that contain a horminone core have been isolated and characterized using a variety of spectroscopic methods, X-ray structural reports of these compounds are relatively scarce. A search of the Cambridge Structural Database (Version 5.26 with updates to August 2006 2005?; Allen, 2002) revealed only seven structures containing the horminone core (refcodes BANREN, BANRIR, CONCYT, GAMLOV, HACGUN, KEXPUY and QICLIX).

The structure of (I) is shown in Fig. 1. The bond distances and angles are normal and similar to those reported for other compounds that contain the horminone core. The six-membered ring of the p-quinone group is in a slight boat conformation, with atoms C8/C9/C12/C13 essentially planar (r.m.s. deviation 0.028 Å), while atoms C11 and C14 are 0.280 (4) and 0.147 (3) Å, respectively, from this plane. In the central cyclohexene ring, atoms C7–C10 are essentially planar (r.m.s. deviation 0.002 Å), with atoms C5 and C6 − 0.566 (4) and 0.212 (4) Å, respectively, from this plane. The conformational analysis of that ring (Duax et al., 1976) shows that the conformation is a half-chair, with a local pseudo-twofold axis running through the midpoints of the C5—C6 and C8—C9 bonds. The cyclohexene ring is trans-fused to this terminal cyclohexane ring, with the methyl group and H atom at the fusion sites being in trans-positions. The terminal cyclohexane ring adopts a chair conformation.

In the crystal structure, molecules related by 2₁ screw axes are linked via a single weak intermolecular C—H···O hydrogen bond to form one-dimensional chains in the b axis direction (Table 2. Fig. 2).

In view of the use of folk medicinal plants as a guide to the development of new pharmaceuticals, studies are currently in progress in our laboratories to explore the structure–activity relationship of natural products isolated from a variety of Jamaican endemic plants.

S2. Experimental

The plant materials were collected in St. Mary, Jamaica, West Indies. A voucher specimen was deposited in the Botany Herbarium, UWI (accession No.35124). The air-dried and milled roots of Hyptis verticillata (6.987 kg) were extracted with hexane (2 × 8 l) and then with dichloromethane (2 × 6 l). Both extractions were performed over a 4 d period at room temperature. The dichloromethane extract was then evaporated in vacuo to give a dark-yellow residue (23.69 g) which was subjected to column chromatography (column material?). A crude mixture of 7-acetyl horminone and its methoxy derivative was obtained after elution with (1–5%) ethyl acetate–hexane. The mixture was triturated using cold chloroform to give the residue, 7-acetyl horminone, and the triturant, 7-acetyl-12-methoxy horminone. When 7-acetyl-12-methoxy horminone was allowed to stand in 10% ethyl acetate–hexane solution at room temperature for several days, yellow needles of (I) were formed.

S3. Refinement

In the absence of significant anomalous dispersion effects, Friedel pairs were merged. The enantiomer is assigned arbitrarily. All H atoms were included in calculated positions, with C—H distances ranging from 0.98 and 1.00 Å, and were refined in a riding-model approximation, with U_iso(H) = 1.2U_eq(C), or 1.5U_eq(C) for methyl H atoms.

Computing details

Data collection: COLLECT (Nonius, 2002); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXTL/PC (Sheldrick, 2001); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXTL/PC.

Figures

	Fig. 1. A view of (I), showing displacement ellipsoids drawn at the 30% probability level.
	Fig. 2. A view of the hydrogen bonds (dashed lines) in the crystal structure of (I). Only the H atoms of the methyl group are shown, as one of these H atoms is involved in the hydrogen bonding.

7-acetyl-12-methoxyabiet-8,12-diene-11,14-dione

Crystal data

C23H32O5	F(000) = 420
Mr = 388.49	Dx = 1.251 Mg m^−3
Monoclinic, P21	Melting point = 449–451 K
Hall symbol: P 2yb	Mo Kα radiation, λ = 0.71073 Å
a = 6.0049 (4) Å	Cell parameters from 5577 reflections
b = 14.6876 (5) Å	θ = 2.6–27.5°
c = 11.8412 (7) Å	µ = 0.09 mm^−1
β = 99.190 (2)°	T = 150 K
V = 1030.96 (10) Å^3	Plate cut from needle, yellow
Z = 2	0.26 × 0.20 × 0.16 mm

Data collection

Bruker Nonius KappaCCD area-detector diffractometer	2444 independent reflections
Radiation source: fine-focus sealed tube	2018 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.053
Detector resolution: 9 pixels mm^-1	θmax = 27.5°, θmin = 3.3°
ϕ scans and ω scans with κ offsets	h = −7→7
Absorption correction: multi-scan (SORTAV; Blessing, 1995)	k = −16→18
Tmin = 0.838, Tmax = 0.988	l = −14→15
8813 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.040	H-atom parameters constrained
wR(F^2) = 0.099	w = 1/[σ^2(Fo^2) + (0.052P)^2 + 0.083P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max < 0.001
2444 reflections	Δρmax = 0.20 e Å^−3
261 parameters	Δρmin = −0.20 e Å^−3
1 restraint	Extinction correction: SHELXTL/PC (Sheldrick, 2001), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.023 (5)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.0946 (3)	0.30710 (12)	0.01011 (15)	0.0348 (4)
O3	0.4693 (3)	0.42094 (12)	0.01278 (14)	0.0315 (4)
O2	0.3827 (3)	0.45794 (13)	0.39619 (15)	0.0356 (4)
O4	0.4407 (3)	0.25969 (12)	0.48182 (13)	0.0286 (4)
O5	0.3288 (4)	0.28525 (14)	0.65190 (16)	0.0433 (5)
C11	0.2137 (4)	0.32275 (16)	0.1017 (2)	0.0265 (5)
C12	0.3916 (4)	0.39493 (15)	0.1089 (2)	0.0254 (5)
C13	0.4487 (4)	0.44349 (16)	0.2061 (2)	0.0256 (5)
C14	0.3631 (4)	0.41183 (16)	0.3090 (2)	0.0255 (5)
C8	0.2515 (4)	0.32046 (16)	0.3088 (2)	0.0248 (5)
C9	0.1787 (4)	0.27622 (15)	0.2104 (2)	0.0247 (5)
C10	0.0469 (4)	0.18638 (16)	0.2039 (2)	0.0251 (5)
C1	0.1240 (4)	0.12128 (16)	0.1148 (2)	0.0287 (5)
H1A	0.0783	0.1469	0.0372	0.034*
H1B	0.2906	0.1168	0.1291	0.034*
C2	0.0233 (5)	0.02619 (17)	0.1192 (2)	0.0321 (6)
H2A	−0.1426	0.0298	0.0976	0.038*
H2B	0.0817	−0.0134	0.0629	0.038*
C3	0.0804 (4)	−0.01599 (17)	0.2376 (2)	0.0319 (6)
H3A	0.2454	−0.0259	0.2550	0.038*
H3B	0.0062	−0.0762	0.2370	0.038*
C4	0.0072 (4)	0.04253 (17)	0.3335 (2)	0.0295 (6)
C5	0.1019 (4)	0.14002 (16)	0.3234 (2)	0.0260 (5)
H5A	0.2695	0.1322	0.3366	0.031*
C6	0.0557 (4)	0.20604 (17)	0.4165 (2)	0.0299 (5)
H6A	−0.1020	0.2278	0.3992	0.036*
H6B	0.0750	0.1740	0.4911	0.036*
C7	0.2150 (4)	0.28666 (17)	0.4244 (2)	0.0274 (5)
H7A	0.1558	0.3372	0.4678	0.033*
C15	0.5950 (4)	0.52852 (17)	0.2168 (2)	0.0284 (5)
H15A	0.5885	0.5552	0.2939	0.034*
C16	0.8413 (5)	0.5041 (2)	0.2140 (3)	0.0412 (7)
H16A	0.8943	0.4614	0.2761	0.062*
H16B	0.9335	0.5594	0.2236	0.062*
H16C	0.8541	0.4757	0.1404	0.062*
C17	0.5104 (5)	0.60196 (17)	0.1284 (2)	0.0372 (7)
H17A	0.3488	0.6120	0.1274	0.056*
H17B	0.5358	0.5820	0.0525	0.056*
H17C	0.5926	0.6588	0.1487	0.056*
C21	0.4799 (5)	0.35769 (19)	−0.0793 (2)	0.0339 (6)
H21A	0.6087	0.3729	−0.1172	0.051*
H21B	0.3403	0.3615	−0.1347	0.051*
H21C	0.4979	0.2957	−0.0486	0.051*
C20	−0.2051 (4)	0.21198 (18)	0.1665 (2)	0.0321 (6)
H20A	−0.2179	0.2573	0.1051	0.048*
H20B	−0.2655	0.2373	0.2319	0.048*
H20C	−0.2909	0.1574	0.1389	0.048*
C18	0.1179 (5)	0.0011 (2)	0.4482 (2)	0.0379 (6)
H18A	0.0864	−0.0644	0.4483	0.057*
H18B	0.0565	0.0304	0.5109	0.057*
H18C	0.2814	0.0109	0.4583	0.057*
C19	−0.2492 (4)	0.0379 (2)	0.3300 (3)	0.0380 (6)
H19A	−0.2911	−0.0232	0.3526	0.057*
H19B	−0.3256	0.0509	0.2523	0.057*
H19C	−0.2947	0.0829	0.3830	0.057*
C22	0.4728 (5)	0.26244 (19)	0.5976 (2)	0.0323 (6)
C23	0.7069 (5)	0.2324 (2)	0.6462 (2)	0.0399 (7)
H23A	0.7338	0.2428	0.7290	0.060*
H23B	0.8163	0.2672	0.6107	0.060*
H23C	0.7236	0.1674	0.6309	0.060*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0405 (11)	0.0364 (10)	0.0251 (9)	−0.0058 (8)	−0.0026 (8)	0.0022 (7)
O3	0.0448 (11)	0.0274 (9)	0.0239 (9)	−0.0043 (8)	0.0106 (8)	−0.0017 (7)
O2	0.0395 (11)	0.0394 (10)	0.0286 (10)	−0.0070 (8)	0.0078 (8)	−0.0093 (8)
O4	0.0275 (9)	0.0370 (10)	0.0211 (8)	0.0015 (7)	0.0038 (7)	0.0003 (7)
O5	0.0458 (12)	0.0589 (14)	0.0268 (10)	0.0073 (10)	0.0108 (9)	−0.0023 (9)
C11	0.0293 (13)	0.0272 (13)	0.0228 (12)	0.0026 (10)	0.0030 (10)	−0.0007 (9)
C12	0.0271 (13)	0.0232 (12)	0.0260 (13)	0.0034 (9)	0.0044 (10)	0.0033 (9)
C13	0.0224 (12)	0.0278 (12)	0.0266 (13)	0.0034 (9)	0.0037 (9)	−0.0008 (9)
C14	0.0257 (12)	0.0276 (12)	0.0231 (12)	0.0035 (10)	0.0036 (10)	−0.0012 (10)
C8	0.0215 (11)	0.0292 (12)	0.0238 (12)	0.0048 (9)	0.0041 (9)	0.0010 (9)
C9	0.0221 (12)	0.0269 (13)	0.0254 (12)	0.0026 (9)	0.0047 (9)	0.0016 (9)
C10	0.0190 (12)	0.0302 (13)	0.0258 (12)	−0.0005 (9)	0.0026 (9)	0.0004 (10)
C1	0.0297 (14)	0.0296 (13)	0.0266 (13)	−0.0025 (10)	0.0038 (11)	−0.0018 (10)
C2	0.0322 (14)	0.0306 (13)	0.0327 (14)	−0.0014 (10)	0.0031 (11)	−0.0030 (11)
C3	0.0287 (14)	0.0280 (13)	0.0381 (15)	−0.0017 (10)	0.0029 (11)	0.0009 (10)
C4	0.0231 (13)	0.0330 (14)	0.0325 (13)	−0.0017 (10)	0.0043 (10)	0.0074 (10)
C5	0.0186 (12)	0.0334 (13)	0.0263 (13)	−0.0001 (9)	0.0045 (10)	0.0012 (10)
C6	0.0275 (13)	0.0368 (14)	0.0267 (13)	−0.0007 (10)	0.0085 (10)	0.0022 (10)
C7	0.0269 (13)	0.0327 (13)	0.0234 (12)	0.0025 (10)	0.0065 (10)	−0.0008 (9)
C15	0.0279 (13)	0.0273 (12)	0.0300 (13)	−0.0016 (10)	0.0044 (10)	−0.0012 (10)
C16	0.0288 (15)	0.0464 (16)	0.0479 (18)	−0.0032 (12)	0.0047 (13)	−0.0024 (13)
C17	0.0487 (18)	0.0266 (13)	0.0355 (15)	−0.0019 (11)	0.0046 (13)	0.0028 (11)
C21	0.0459 (16)	0.0345 (14)	0.0225 (12)	−0.0027 (11)	0.0095 (12)	−0.0024 (10)
C20	0.0261 (14)	0.0341 (14)	0.0349 (14)	0.0011 (10)	0.0006 (11)	0.0028 (10)
C18	0.0351 (15)	0.0396 (15)	0.0379 (15)	−0.0036 (11)	0.0023 (12)	0.0112 (11)
C19	0.0269 (14)	0.0427 (15)	0.0453 (16)	−0.0060 (12)	0.0088 (12)	0.0071 (13)
C22	0.0422 (16)	0.0325 (13)	0.0227 (12)	−0.0039 (11)	0.0067 (11)	0.0014 (10)
C23	0.0396 (16)	0.0530 (17)	0.0261 (14)	−0.0001 (12)	0.0019 (12)	0.0055 (12)

Geometric parameters (Å, º)

O1—C11	1.221 (3)	C5—C6	1.527 (3)
O3—C12	1.352 (3)	C5—H5A	1.0000
O3—C21	1.442 (3)	C6—C7	1.515 (3)
O2—C14	1.224 (3)	C6—H6A	0.9900
O4—C22	1.354 (3)	C6—H6B	0.9900
O4—C7	1.470 (3)	C7—H7A	1.0000
O5—C22	1.205 (3)	C15—C16	1.528 (4)
C11—C12	1.498 (3)	C15—C17	1.532 (4)
C11—C9	1.501 (3)	C15—H15A	1.0000
C12—C13	1.350 (3)	C16—H16A	0.9800
C13—C14	1.472 (3)	C16—H16B	0.9800
C13—C15	1.521 (3)	C16—H16C	0.9800
C14—C8	1.500 (3)	C17—H17A	0.9800
C8—C9	1.345 (3)	C17—H17B	0.9800
C8—C7	1.504 (3)	C17—H17C	0.9800
C9—C10	1.534 (3)	C21—H21A	0.9800
C10—C1	1.549 (3)	C21—H21B	0.9800
C10—C20	1.553 (3)	C21—H21C	0.9800
C10—C5	1.557 (3)	C20—H20A	0.9800
C1—C2	1.526 (4)	C20—H20B	0.9800
C1—H1A	0.9900	C20—H20C	0.9800
C1—H1B	0.9900	C18—H18A	0.9800
C2—C3	1.521 (4)	C18—H18B	0.9800
C2—H2A	0.9900	C18—H18C	0.9800
C2—H2B	0.9900	C19—H19A	0.9800
C3—C4	1.543 (4)	C19—H19B	0.9800
C3—H3A	0.9900	C19—H19C	0.9800
C3—H3B	0.9900	C22—C23	1.498 (4)
C4—C19	1.536 (4)	C23—H23A	0.9800
C4—C18	1.539 (4)	C23—H23B	0.9800
C4—C5	1.552 (3)	C23—H23C	0.9800
C12—O3—C21	121.16 (19)	C5—C6—H6B	109.5
C22—O4—C7	115.58 (19)	H6A—C6—H6B	108.1
O1—C11—C12	119.7 (2)	O4—C7—C8	104.60 (18)
O1—C11—C9	122.2 (2)	O4—C7—C6	110.11 (19)
C12—C11—C9	118.0 (2)	C8—C7—C6	112.6 (2)
C13—C12—O3	119.6 (2)	O4—C7—H7A	109.8
C13—C12—C11	120.3 (2)	C8—C7—H7A	109.8
O3—C12—C11	119.4 (2)	C6—C7—H7A	109.8
C12—C13—C14	117.7 (2)	C13—C15—C16	110.7 (2)
C12—C13—C15	124.7 (2)	C13—C15—C17	113.4 (2)
C14—C13—C15	117.6 (2)	C16—C15—C17	111.5 (2)
O2—C14—C13	121.6 (2)	C13—C15—H15A	107.0
O2—C14—C8	118.6 (2)	C16—C15—H15A	107.0
C13—C14—C8	119.7 (2)	C17—C15—H15A	107.0
C9—C8—C14	121.1 (2)	C15—C16—H16A	109.5
C9—C8—C7	123.7 (2)	C15—C16—H16B	109.5
C14—C8—C7	115.1 (2)	H16A—C16—H16B	109.5
C8—C9—C11	116.9 (2)	C15—C16—H16C	109.5
C8—C9—C10	123.6 (2)	H16A—C16—H16C	109.5
C11—C9—C10	119.34 (19)	H16B—C16—H16C	109.5
C9—C10—C1	110.94 (19)	C15—C17—H17A	109.5
C9—C10—C20	106.11 (19)	C15—C17—H17B	109.5
C1—C10—C20	109.81 (19)	H17A—C17—H17B	109.5
C9—C10—C5	107.31 (18)	C15—C17—H17C	109.5
C1—C10—C5	107.82 (19)	H17A—C17—H17C	109.5
C20—C10—C5	114.8 (2)	H17B—C17—H17C	109.5
C2—C1—C10	112.2 (2)	O3—C21—H21A	109.5
C2—C1—H1A	109.2	O3—C21—H21B	109.5
C10—C1—H1A	109.2	H21A—C21—H21B	109.5
C2—C1—H1B	109.2	O3—C21—H21C	109.5
C10—C1—H1B	109.2	H21A—C21—H21C	109.5
H1A—C1—H1B	107.9	H21B—C21—H21C	109.5
C3—C2—C1	111.9 (2)	C10—C20—H20A	109.5
C3—C2—H2A	109.2	C10—C20—H20B	109.5
C1—C2—H2A	109.2	H20A—C20—H20B	109.5
C3—C2—H2B	109.2	C10—C20—H20C	109.5
C1—C2—H2B	109.2	H20A—C20—H20C	109.5
H2A—C2—H2B	107.9	H20B—C20—H20C	109.5
C2—C3—C4	113.7 (2)	C4—C18—H18A	109.5
C2—C3—H3A	108.8	C4—C18—H18B	109.5
C4—C3—H3A	108.8	H18A—C18—H18B	109.5
C2—C3—H3B	108.8	C4—C18—H18C	109.5
C4—C3—H3B	108.8	H18A—C18—H18C	109.5
H3A—C3—H3B	107.7	H18B—C18—H18C	109.5
C19—C4—C18	107.2 (2)	C4—C19—H19A	109.5
C19—C4—C3	111.0 (2)	C4—C19—H19B	109.5
C18—C4—C3	107.2 (2)	H19A—C19—H19B	109.5
C19—C4—C5	114.7 (2)	C4—C19—H19C	109.5
C18—C4—C5	108.7 (2)	H19A—C19—H19C	109.5
C3—C4—C5	107.83 (19)	H19B—C19—H19C	109.5
C6—C5—C4	114.8 (2)	O5—C22—O4	123.4 (2)
C6—C5—C10	110.0 (2)	O5—C22—C23	125.9 (2)
C4—C5—C10	116.51 (19)	O4—C22—C23	110.7 (2)
C6—C5—H5A	104.7	C22—C23—H23A	109.5
C4—C5—H5A	104.7	C22—C23—H23B	109.5
C10—C5—H5A	104.7	H23A—C23—H23B	109.5
C7—C6—C5	110.8 (2)	C22—C23—H23C	109.5
C7—C6—H6A	109.5	H23A—C23—H23C	109.5
C5—C6—H6A	109.5	H23B—C23—H23C	109.5
C7—C6—H6B	109.5
C21—O3—C12—C13	158.7 (2)	C5—C10—C1—C2	53.8 (3)
C21—O3—C12—C11	−31.5 (3)	C10—C1—C2—C3	−56.8 (3)
O1—C11—C12—C13	148.4 (2)	C1—C2—C3—C4	56.1 (3)
C9—C11—C12—C13	−27.7 (3)	C2—C3—C4—C19	74.5 (3)
O1—C11—C12—O3	−21.4 (3)	C2—C3—C4—C18	−168.7 (2)
C9—C11—C12—O3	162.6 (2)	C2—C3—C4—C5	−51.8 (3)
O3—C12—C13—C14	−179.1 (2)	C19—C4—C5—C6	59.1 (3)
C11—C12—C13—C14	11.2 (3)	C18—C4—C5—C6	−60.9 (3)
O3—C12—C13—C15	0.9 (3)	C3—C4—C5—C6	−176.8 (2)
C11—C12—C13—C15	−168.8 (2)	C19—C4—C5—C10	−71.6 (3)
C12—C13—C14—O2	−170.6 (2)	C18—C4—C5—C10	168.5 (2)
C15—C13—C14—O2	9.4 (3)	C3—C4—C5—C10	52.6 (3)
C12—C13—C14—C8	10.2 (3)	C9—C10—C5—C6	53.6 (2)
C15—C13—C14—C8	−169.76 (19)	C1—C10—C5—C6	173.15 (19)
O2—C14—C8—C9	164.6 (2)	C20—C10—C5—C6	−64.1 (3)
C13—C14—C8—C9	−16.2 (3)	C9—C10—C5—C4	−173.58 (19)
O2—C14—C8—C7	−11.5 (3)	C1—C10—C5—C4	−54.0 (3)
C13—C14—C8—C7	167.7 (2)	C20—C10—C5—C4	68.7 (3)
C14—C8—C9—C11	−0.2 (3)	C4—C5—C6—C7	161.0 (2)
C7—C8—C9—C11	175.5 (2)	C10—C5—C6—C7	−65.3 (3)
C14—C8—C9—C10	−175.0 (2)	C22—O4—C7—C8	154.0 (2)
C7—C8—C9—C10	0.8 (4)	C22—O4—C7—C6	−84.8 (3)
O1—C11—C9—C8	−154.7 (2)	C9—C8—C7—O4	110.3 (3)
C12—C11—C9—C8	21.3 (3)	C14—C8—C7—O4	−73.8 (2)
O1—C11—C9—C10	20.3 (3)	C9—C8—C7—C6	−9.3 (3)
C12—C11—C9—C10	−163.8 (2)	C14—C8—C7—C6	166.7 (2)
C8—C9—C10—C1	−140.5 (2)	C5—C6—C7—O4	−75.6 (2)
C11—C9—C10—C1	44.9 (3)	C5—C6—C7—C8	40.8 (3)
C8—C9—C10—C20	100.3 (3)	C12—C13—C15—C16	−72.6 (3)
C11—C9—C10—C20	−74.3 (3)	C14—C13—C15—C16	107.4 (3)
C8—C9—C10—C5	−22.9 (3)	C12—C13—C15—C17	53.6 (3)
C11—C9—C10—C5	162.5 (2)	C14—C13—C15—C17	−126.4 (2)
C9—C10—C1—C2	171.1 (2)	C7—O4—C22—O5	0.0 (4)
C20—C10—C1—C2	−71.9 (3)	C7—O4—C22—C23	179.2 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C18—H18C···O2^i	0.98	2.56	3.320 (3)	135

Symmetry code: (i) −x+1, y−1/2, −z+1.