4,5,7,8,17-Penta­hydr­oxy-14,18-dimethyl-6-methyl­ene-3,10-dioxapenta­cyclo­[9.8.0.01,7.04,19.013,18]nona­dec-14-ene-9,16-dione methanol solvate dihydrate

Teh, C.H.; Teoh, S.C.; Yeap, C.S.; Chan, K.L.; Fun, H.-K.

doi:10.1107/S1600536809010502

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 4| April 2009| Pages o898-o899

doi:10.1107/S1600536809010502

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4,5,7,8,17-Pentahydroxy-14,18-dimethyl-6-methylene-3,10-dioxapentacyclo[9.8.0.0^1,7.0^4,19.0^13,18]nonadec-14-ene-9,16-dione methanol solvate dihydrate

Chin Hoe Teh,^a Siew Chin Teoh,^b Chin Sing Yeap,^b Kit Lam Chan ^a ‡ and Hoong-Kun Fun ^b ^*

^aSchool of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia, and ^bX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia
^*Correspondence e-mail: hkfun@usm.my

(Received 18 March 2009; accepted 22 March 2009; online 28 March 2009)

The title quassinoid compound, C₂₀H₂₄O₉·CH₃OH·2H₂O, is a natural eurycomanone isolated from the roots of Eurycoma longifolia. The molecules contain a fused five-ring system, with one tetrahydrofuran ring adopting an envelope conformation, one tetrahydropyran-2-one ring in a screw boat conformation, one cyclohexenone ring in a half-chair conformation and two cyclohexane rings in chair conformations. Intramolecular C—H⋯O interactions generate S(5) ring motifs and an O—H⋯O interaction generates an S(7) ring motif. In the crystal, molecules are linked via intermolecular O—H⋯O interactions along the b axis and further stacked along a axis. The absolute configuration of the title compound was inferred from previously solved structures of its analogues.

Related literature

For bond-length data, see Allen et al. (1987 ). For hydrogen-bond motifs, see Bernstein et al. (1995 ). For ring conformations, see Cremer & Pople (1975 ). For quassinoids and bioactivity, see Itokawa et al. (1993 ); Chan et al. (1992 ); Kardono et al. (1991 ); Itokawa et al. (1992 ); Morita et al. (1992 ); Morita et al. (1993 ); Tada et al. (1991 ); Ang et al. (1995 ); Chan et al. (2004 ). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 ).

Experimental

Crystal data

C₂₀H₂₄O₉·CH₄O·2H₂O
M_r = 476.47
Orthorhombic, P 2₁ 2₁ 2₁
a = 9.1817 (1) Å
b = 10.7806 (2) Å
c = 21.7817 (3) Å
V = 2156.04 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 100 K
0.43 × 0.28 × 0.11 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ) T_min = 0.950, T_max = 0.987
27636 measured reflections
3577 independent reflections
3352 reflections with I > 2σ(I)
R_int = 0.033

Refinement

R[F² > 2σ(F²)] = 0.043
wR(F²) = 0.127
S = 1.09
3577 reflections
307 parameters
H-atom parameters constrained
Δρ_max = 1.08 e Å⁻³
Δρ_min = −0.46 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1W—H1W1⋯O4ⁱ	0.88	1.94	2.810 (2)	169
O2—H2⋯O2Wⁱⁱ	0.82	1.85	2.656 (3)	169
O1W—H2W1⋯O3ⁱⁱⁱ	0.84	2.06	2.873 (3)	163
O3—H3⋯O2	0.82	1.71	2.525 (2)	171
O2W—H1W2⋯O8	0.95	2.03	2.950 (3)	164
O2W—H2W2⋯O10	0.85	1.91	2.760 (3)	179
O5—H5⋯O3^iv	0.82	1.99	2.805 (2)	172
O6—H6⋯O9^v	0.82	2.14	2.848 (2)	144
O7—H7⋯O1W^vi	0.82	1.84	2.653 (3)	171
O10—H10⋯O7^vii	0.82	2.29	3.011 (3)	147
O10—H10⋯O8^vii	0.82	2.23	2.911 (3)	140
C1—H1A⋯O9	0.98	2.48	2.936 (3)	108
C1—H1A⋯O1ⁱⁱⁱ	0.98	2.56	3.507 (3)	162
C7—H7A⋯O5	0.98	2.38	2.856 (3)	109
C12—H12A⋯O1ⁱⁱⁱ	0.98	2.47	3.168 (3)	128
C17—H17A⋯O10^v	0.97	2.60	3.428 (3)	144
C17—H17B⋯O6	0.97	2.50	2.929 (3)	107
C19—H19B⋯O2	0.96	2.56	2.957 (3)	105
Symmetry codes: (i) x+1, y+1, z; (ii) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+2]$ ; (iii) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+2]$ ; (iv) $[x+{\script{1\over 2}}, -y-{\script{1\over 2}}, -z+2]$ ; (v) $[-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (vi) x, y-1, z; (vii) $[-x+2, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809010502/at2747sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809010502/at2747Isup2.hkl

checkCIF report

Comment top

Eurycoma longifolia Jack is a tall, slender shrub-tree, commonly found in lowland forests below 500 meters above sea level in Southeast Asia. The roots of this Simaroubaceae plant are used in folk medicine for intermittent fever (malaria), dysentery, glandular swelling and aphrodisiac properties. Various classes of chemical constituents (Itokawa et al., 1993, Chan et al., 1992, Kardono et al., 1991, Itokawa et al., 1992, Morita et al., 1992, Morita et al., 1993) have been identified and some have shown antiulcer (Tada et al., 1991), cytotoxic (Kardono et al., 1991, Itokawa et al., 1992) and antimalarial (Ang et al., 1995, Chan et al., 2004) activities. In our continuing search for the bioactive compounds from E. longifolia, we have isolated eurycomanone (1), a quassinoid in crystalline form.

The title compound (Fig. 1), contains quassinoid, one molecule of methanol and two molecules of water solvents. The bond lengths and angles are within normal ranges (Allen et al., 1987). The molecule of the title compound contains a fused five-ring system A/B/C/D/E (Scheme 1). The A/B and B/D junctions are trans-fused, whereas B/C, B/E and C/D are cis-fused (Fig 1). The cyclohexenone ring A (C1—C6) has a half-chair conformation with puckering parameters of Q = 0.507 (2) Å, Θ = 130.2 (3)° and ϕ = 97.3 (4)°. The cyclohexane ring B (C1-C6-C7-C16-C14-C15) and D (C7-C8-C9-C10-C11-C16) adopt a chair conformation with puckering parameters of Q = 0.565 (2) Å, Θ = 154.6 (3)° and ϕ = 179.8 (6)° and Q = 0.660 (2) Å, Θ = 151.68 (17)° and ϕ = 183.1 (4)° respectively. The tetrahydro-pyran-2-one ring C (O9-C13-C12-C11-C16-14) has a screw boat conformation with puckering parameters Q = 0.502 (3) Å, Θ = 38.4 (2)° and ϕ = 193.4 (5)°. The tetrahydro-furan ring E (C7-C8-O4-C17-C16) is in an envelope conformation with puckering parameters of Q = 0.450 (2) Å and ϕ = 254.5 (3)°.

The intramolecular interactions C1—H1A···O9, C17—H17B···O6, C19—H19B···O2 and C7—H7A···O5 generate S(5) ring motifs, and O3—H3···O2 generates an S(7) ring motif (Bernstein et al., 1995). The crystal packing shows that the molecules were linked via intermolecular O—H···O interactions along b axis and further stacked along a axis (Fig 2). The absolute configuration of the title compound was inferred from previously solved structures of its analogues (Tada et al., 1991).

Related literature top

For bond-length data, see Allen et al. (1987). For hydrogen-bond motifs, see Bernstein et al. (1995). For ring conformations, see Cremer & Pople (1975). For quassinoids and bioactivity, see Itokawa et al. (1993); Chan et al. (1992); Kardono et al. (1991); Itokawa et al. (1992); Morita et al. (1992); Morita et al. (1993); Tada et al. (1991); Ang et al. (1995); Chan et al. (2004). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986).

Experimental top

The air-dried powdered roots of E. longifolia (11.6 kg) were extracted with MeOH. The MeOH extract on evaporation to dryness yielded 485 g of dark brown residue which was next chromatographed on a Diaion HP 20 column using H₂O-MeOH (1:0 - 0:1) gradient mixtures to afford 4 fractions (Fr 1 - 4). Fr 2 was concentrated under vacuum to give 52.2 g of residue. The residue was resuspended in water and then partitioned successively with ethyl acetate and saturated n-butanol to yield three subfractions. The n-BuOH subfraction (20.4 g) was further fractionated on a silica gel column using CHCl₃-MeOH (1:0 - 1:1) gradient mixtures to obtain 7 portions (A1-A7). A3 was further purified by centrifugal silica gel TLC with CHCl₃-MeOH (1:0 - 1:1) gradient mixtures. Upon solvent removal, the residue obtained on subsequent recrystallization from CHCl₃-MeOH (9:1, v/v) at room temperature afforded 1 as colourless crystals (75.3 mg).

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top

	Fig. 1. The molecular structure of the title compound with atom labels and 50% probability ellipsoids for non-H atoms. Intramolecular hydrogen bonds are shown as dashed lines.
	Fig. 2. The crystal packing of (I), shows that the molecules were linked via intermolecular O—H···O interactions along b axis and further stacked along a axis. Intermolecular interactions are drawn as dashed lines.

4,5,7,8,17-pentahydroxy-14,18-dimethyl-6-methylene-3,10-dioxapentacyclo [9.8.0.0^1,7.0^4,19.0^13,18]nonadec-14-ene-9,16-dione methanol solvate dihydrate top

Crystal data top

C₂₀H₂₄O₉·CH₄O·2H₂O	F(000) = 1016
M_r = 476.47	D_x = 1.468 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9889 reflections
a = 9.1817 (1) Å	θ = 2.4–30.1°
b = 10.7806 (2) Å	µ = 0.12 mm⁻¹
c = 21.7817 (3) Å	T = 100 K
V = 2156.04 (6) Å³	Block, colourless
Z = 4	0.43 × 0.28 × 0.11 mm

Data collection top

Bruker SMART APEXII CCD area-detector diffractometer	3577 independent reflections
Radiation source: fine-focus sealed tube	3352 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.033
ϕ and ω scans	θ_max = 30.1°, θ_min = 1.9°
Absorption correction: multi-scan (SADABS; Bruker, 2005)	h = −12→12
T_min = 0.950, T_max = 0.987	k = −15→15
27636 measured reflections	l = −29→30

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)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.127	H-atom parameters constrained
S = 1.09	w = 1/[σ²(F_o²) + (0.0739P)² + 1.2123P] where P = (F_o² + 2F_c²)/3
3577 reflections	(Δ/σ)_max < 0.001
307 parameters	Δρ_max = 1.08 e Å⁻³
0 restraints	Δρ_min = −0.46 e Å⁻³

Crystal data top

C₂₀H₂₄O₉·CH₄O·2H₂O	V = 2156.04 (6) Å³
M_r = 476.47	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 9.1817 (1) Å	µ = 0.12 mm⁻¹
b = 10.7806 (2) Å	T = 100 K
c = 21.7817 (3) Å	0.43 × 0.28 × 0.11 mm

Data collection top

Bruker SMART APEXII CCD area-detector diffractometer	3577 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2005)	3352 reflections with I > 2σ(I)
T_min = 0.950, T_max = 0.987	R_int = 0.033
27636 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	0 restraints
wR(F²) = 0.127	H-atom parameters constrained
S = 1.09	Δρ_max = 1.08 e Å⁻³
3577 reflections	Δρ_min = −0.46 e Å⁻³
307 parameters

Special details top

Experimental. The crystal was placed in the cold stream of an Oxford Cyrosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1)K.

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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
O1	0.1926 (2)	0.29462 (17)	1.07263 (8)	0.0182 (4)
O2	0.3034 (2)	0.07030 (16)	1.05042 (8)	0.0175 (4)
H2	0.3223	0.0997	1.0842	0.026*
O3	0.28241 (19)	−0.14352 (15)	1.00393 (7)	0.0117 (3)
H3	0.2817	−0.0757	1.0210	0.018*
O4	0.22993 (18)	−0.17614 (15)	0.90312 (7)	0.0118 (3)
O5	0.58130 (19)	−0.16373 (15)	0.97902 (7)	0.0129 (3)
H5	0.6465	−0.2146	0.9843	0.019*
O6	0.5152 (2)	−0.13426 (15)	0.77017 (7)	0.0127 (3)
H6	0.4834	−0.2045	0.7648	0.019*
O7	0.78562 (19)	−0.09069 (17)	0.82090 (8)	0.0147 (3)
H7	0.8241	−0.1258	0.8501	0.022*
O8	0.74680 (19)	0.14137 (17)	0.77962 (8)	0.0167 (4)
O9	0.51228 (19)	0.13846 (15)	0.79549 (7)	0.0126 (3)
C1	0.3189 (3)	0.22030 (19)	0.89489 (10)	0.0101 (4)
H1A	0.4255	0.2249	0.8946	0.012*
C2	0.2671 (3)	0.3479 (2)	0.91422 (11)	0.0130 (4)
C3	0.2330 (3)	0.3740 (2)	0.97285 (11)	0.0152 (4)
H3A	0.2023	0.4536	0.9830	0.018*
C4	0.2431 (3)	0.2802 (2)	1.02085 (11)	0.0133 (4)
C5	0.3254 (3)	0.1614 (2)	1.00468 (10)	0.0112 (4)
H5A	0.4296	0.1810	1.0035	0.013*
C6	0.2803 (2)	0.11364 (19)	0.94038 (10)	0.0093 (4)
C7	0.3786 (3)	0.00071 (19)	0.92185 (9)	0.0086 (4)
H7A	0.4783	0.0189	0.9351	0.010*
C8	0.3392 (2)	−0.1308 (2)	0.94491 (9)	0.0094 (4)
C9	0.4726 (3)	−0.21530 (19)	0.93946 (9)	0.0106 (4)
H9A	0.4470	−0.2984	0.9542	0.013*
C10	0.5283 (3)	−0.2248 (2)	0.87386 (10)	0.0108 (4)
C11	0.5208 (3)	−0.10845 (19)	0.83436 (9)	0.0094 (4)
C12	0.6596 (3)	−0.0292 (2)	0.84086 (10)	0.0105 (4)
H12A	0.6718	−0.0059	0.8840	0.013*
C13	0.6438 (3)	0.0881 (2)	0.80244 (10)	0.0118 (4)
C14	0.3716 (3)	0.0779 (2)	0.80774 (10)	0.0104 (4)
H14A	0.3327	0.0472	0.7687	0.012*
C15	0.2754 (3)	0.1834 (2)	0.82945 (10)	0.0119 (4)
H15A	0.1742	0.1576	0.8288	0.014*
H15B	0.2861	0.2540	0.8022	0.014*
C16	0.3828 (3)	−0.0312 (2)	0.85175 (10)	0.0094 (4)
C17	0.2494 (3)	−0.1166 (2)	0.84404 (10)	0.0118 (4)
H17A	0.1638	−0.0687	0.8332	0.014*
H17B	0.2669	−0.1779	0.8123	0.014*
C18	0.2638 (3)	0.4474 (2)	0.86586 (12)	0.0194 (5)
H18A	0.2506	0.5268	0.8850	0.029*
H18B	0.1846	0.4319	0.8381	0.029*
H18C	0.3540	0.4469	0.8436	0.029*
C19	0.1144 (3)	0.0868 (2)	0.94083 (11)	0.0125 (4)
H19A	0.0618	0.1637	0.9423	0.019*
H19B	0.0904	0.0377	0.9762	0.019*
H19C	0.0883	0.0423	0.9043	0.019*
C20	0.5852 (3)	−0.3310 (2)	0.85366 (11)	0.0154 (5)
H20A	0.5908	−0.3992	0.8797	0.018*
H20B	0.6192	−0.3368	0.8136	0.018*
O10	0.9816 (2)	0.5246 (2)	0.75796 (10)	0.0265 (4)
H10	1.0588	0.5227	0.7390	0.040*
C21	0.9754 (3)	0.6332 (3)	0.79372 (14)	0.0273 (6)
H21A	0.8955	0.6276	0.8220	0.041*
H21B	0.9619	0.7037	0.7674	0.041*
H21C	1.0648	0.6424	0.8162	0.041*
O1W	0.9259 (2)	0.8195 (2)	0.91766 (10)	0.0283 (5)
H1W1	1.0216	0.8137	0.9173	0.042*
H2W1	0.8959	0.7574	0.9371	0.042*
O2W	0.8990 (3)	0.3466 (2)	0.84211 (9)	0.0341 (6)
H1W2	0.8346	0.2908	0.8221	0.051*
H2W2	0.9261	0.4012	0.8161	0.051*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0210 (9)	0.0187 (8)	0.0150 (8)	0.0028 (7)	0.0020 (7)	−0.0043 (7)
O2	0.0321 (10)	0.0119 (7)	0.0086 (7)	0.0001 (7)	0.0005 (7)	−0.0005 (6)
O3	0.0158 (8)	0.0101 (7)	0.0092 (7)	0.0001 (6)	0.0037 (6)	0.0008 (5)
O4	0.0128 (7)	0.0118 (7)	0.0108 (7)	−0.0035 (6)	−0.0018 (6)	0.0019 (6)
O5	0.0141 (8)	0.0127 (7)	0.0121 (7)	0.0033 (6)	−0.0032 (6)	−0.0012 (6)
O6	0.0206 (8)	0.0112 (7)	0.0063 (6)	−0.0015 (7)	0.0009 (6)	−0.0017 (5)
O7	0.0134 (8)	0.0162 (8)	0.0146 (7)	0.0044 (7)	0.0038 (6)	0.0033 (6)
O8	0.0171 (9)	0.0142 (7)	0.0187 (8)	−0.0025 (7)	0.0036 (7)	0.0023 (6)
O9	0.0142 (8)	0.0098 (7)	0.0136 (7)	−0.0001 (6)	0.0011 (6)	0.0032 (6)
C1	0.0122 (9)	0.0079 (8)	0.0102 (9)	0.0010 (7)	0.0000 (8)	0.0003 (7)
C2	0.0134 (10)	0.0084 (9)	0.0173 (10)	0.0004 (8)	−0.0002 (8)	0.0008 (8)
C3	0.0159 (11)	0.0111 (9)	0.0186 (11)	0.0014 (8)	0.0004 (9)	−0.0026 (8)
C4	0.0139 (11)	0.0100 (9)	0.0159 (10)	0.0005 (8)	−0.0012 (8)	−0.0036 (8)
C5	0.0152 (10)	0.0090 (9)	0.0093 (9)	0.0017 (8)	−0.0001 (8)	−0.0021 (7)
C6	0.0113 (9)	0.0073 (8)	0.0093 (8)	0.0015 (8)	−0.0011 (7)	−0.0009 (7)
C7	0.0107 (9)	0.0080 (8)	0.0071 (8)	0.0001 (7)	−0.0005 (8)	−0.0001 (7)
C8	0.0102 (9)	0.0105 (9)	0.0075 (8)	−0.0004 (8)	0.0010 (7)	−0.0001 (7)
C9	0.0141 (10)	0.0088 (8)	0.0088 (8)	0.0002 (8)	0.0002 (8)	0.0002 (7)
C10	0.0142 (10)	0.0093 (8)	0.0089 (9)	0.0000 (8)	0.0001 (8)	−0.0006 (7)
C11	0.0135 (10)	0.0085 (8)	0.0063 (8)	0.0000 (8)	−0.0001 (8)	−0.0007 (7)
C12	0.0134 (10)	0.0094 (9)	0.0088 (8)	0.0001 (8)	0.0000 (8)	−0.0001 (7)
C13	0.0158 (11)	0.0100 (9)	0.0097 (9)	−0.0014 (8)	0.0013 (8)	−0.0020 (7)
C14	0.0128 (10)	0.0103 (9)	0.0081 (9)	−0.0009 (8)	−0.0012 (8)	0.0008 (7)
C15	0.0151 (10)	0.0112 (9)	0.0094 (9)	−0.0001 (8)	−0.0015 (8)	0.0013 (7)
C16	0.0130 (10)	0.0080 (9)	0.0072 (8)	−0.0012 (8)	−0.0015 (7)	0.0003 (7)
C17	0.0132 (10)	0.0128 (10)	0.0094 (9)	−0.0018 (8)	−0.0015 (8)	0.0003 (7)
C18	0.0282 (13)	0.0100 (9)	0.0199 (11)	0.0022 (9)	−0.0016 (10)	0.0030 (8)
C19	0.0107 (10)	0.0120 (9)	0.0147 (10)	0.0004 (8)	0.0005 (8)	−0.0008 (8)
C20	0.0230 (12)	0.0115 (10)	0.0116 (9)	0.0034 (9)	0.0007 (9)	−0.0010 (8)
O10	0.0200 (10)	0.0323 (11)	0.0272 (10)	−0.0057 (9)	−0.0002 (8)	0.0013 (8)
C21	0.0211 (13)	0.0325 (14)	0.0283 (13)	0.0028 (12)	0.0014 (11)	−0.0004 (12)
O1W	0.0188 (9)	0.0352 (11)	0.0310 (10)	−0.0017 (9)	−0.0018 (8)	0.0140 (9)
O2W	0.0531 (15)	0.0298 (11)	0.0195 (9)	−0.0224 (11)	0.0129 (10)	−0.0082 (8)

Geometric parameters (Å, º) top

O1—C4	1.229 (3)	C9—C10	1.521 (3)
O2—C5	1.414 (3)	C9—H9A	0.9800
O2—H2	0.8200	C10—C20	1.333 (3)
O3—C8	1.394 (3)	C10—C11	1.523 (3)
O3—H3	0.8200	C11—C12	1.541 (3)
O4—C8	1.440 (3)	C11—C16	1.562 (3)
O4—C17	1.449 (3)	C12—C13	1.523 (3)
O5—C9	1.431 (3)	C12—H12A	0.9800
O5—H5	0.8200	C14—C15	1.516 (3)
O6—C11	1.426 (2)	C14—C16	1.520 (3)
O6—H6	0.8200	C14—H14A	0.9800
O7—C12	1.402 (3)	C15—H15A	0.9700
O7—H7	0.8200	C15—H15B	0.9700
O8—C13	1.213 (3)	C16—C17	1.542 (3)
O9—C13	1.333 (3)	C17—H17A	0.9700
O9—C14	1.472 (3)	C17—H17B	0.9700
C1—C2	1.516 (3)	C18—H18A	0.9600
C1—C15	1.533 (3)	C18—H18B	0.9600
C1—C6	1.559 (3)	C18—H18C	0.9600
C1—H1A	0.9800	C19—H19A	0.9600
C2—C3	1.345 (3)	C19—H19B	0.9600
C2—C18	1.503 (3)	C19—H19C	0.9600
C3—C4	1.458 (3)	C20—H20A	0.9300
C3—H3A	0.9300	C20—H20B	0.9300
C4—C5	1.528 (3)	O10—C21	1.408 (4)
C5—C6	1.549 (3)	O10—H10	0.8200
C5—H5A	0.9800	C21—H21A	0.9600
C6—C19	1.551 (3)	C21—H21B	0.9600
C6—C7	1.568 (3)	C21—H21C	0.9600
C7—C8	1.547 (3)	O1W—H1W1	0.8814
C7—C16	1.566 (3)	O1W—H2W1	0.8396
C7—H7A	0.9800	O2W—H1W2	0.9487
C8—C9	1.531 (3)	O2W—H2W2	0.8533

C5—O2—H2	109.5	C10—C11—C16	109.83 (18)
C8—O3—H3	109.5	C12—C11—C16	110.67 (17)
C8—O4—C17	108.97 (16)	O7—C12—C13	107.48 (18)
C9—O5—H5	109.5	O7—C12—C11	113.11 (18)
C11—O6—H6	109.5	C13—C12—C11	109.31 (18)
C12—O7—H7	109.5	O7—C12—H12A	109.0
C13—O9—C14	126.43 (17)	C13—C12—H12A	109.0
C2—C1—C15	114.35 (19)	C11—C12—H12A	109.0
C2—C1—C6	114.97 (18)	O8—C13—O9	117.8 (2)
C15—C1—C6	109.89 (17)	O8—C13—C12	123.0 (2)
C2—C1—H1A	105.6	O9—C13—C12	119.14 (19)
C15—C1—H1A	105.6	O9—C14—C15	103.60 (17)
C6—C1—H1A	105.6	O9—C14—C16	113.43 (18)
C3—C2—C18	120.8 (2)	C15—C14—C16	115.04 (18)
C3—C2—C1	121.8 (2)	O9—C14—H14A	108.2
C18—C2—C1	117.3 (2)	C15—C14—H14A	108.2
C2—C3—C4	121.4 (2)	C16—C14—H14A	108.2
C2—C3—H3A	119.3	C14—C15—C1	109.45 (18)
C4—C3—H3A	119.3	C14—C15—H15A	109.8
O1—C4—C3	123.1 (2)	C1—C15—H15A	109.8
O1—C4—C5	120.3 (2)	C14—C15—H15B	109.8
C3—C4—C5	116.6 (2)	C1—C15—H15B	109.8
O2—C5—C4	110.43 (18)	H15A—C15—H15B	108.2
O2—C5—C6	111.59 (18)	C14—C16—C17	109.82 (18)
C4—C5—C6	110.77 (18)	C14—C16—C11	108.34 (18)
O2—C5—H5A	108.0	C17—C16—C11	107.41 (17)
C4—C5—H5A	108.0	C14—C16—C7	116.32 (17)
C6—C5—H5A	108.0	C17—C16—C7	102.56 (17)
C5—C6—C19	108.61 (18)	C11—C16—C7	111.96 (17)
C5—C6—C1	105.59 (16)	O4—C17—C16	105.42 (17)
C19—C6—C1	111.42 (18)	O4—C17—H17A	110.7
C5—C6—C7	109.69 (17)	C16—C17—H17A	110.7
C19—C6—C7	114.94 (18)	O4—C17—H17B	110.7
C1—C6—C7	106.17 (17)	C16—C17—H17B	110.7
C8—C7—C16	96.96 (16)	H17A—C17—H17B	108.8
C8—C7—C6	119.59 (18)	C2—C18—H18A	109.5
C16—C7—C6	115.84 (17)	C2—C18—H18B	109.5
C8—C7—H7A	107.9	H18A—C18—H18B	109.5
C16—C7—H7A	107.9	C2—C18—H18C	109.5
C6—C7—H7A	107.9	H18A—C18—H18C	109.5
O3—C8—O4	106.79 (17)	H18B—C18—H18C	109.5
O3—C8—C9	108.20 (17)	C6—C19—H19A	109.5
O4—C8—C9	107.87 (17)	C6—C19—H19B	109.5
O3—C8—C7	118.47 (17)	H19A—C19—H19B	109.5
O4—C8—C7	105.57 (17)	C6—C19—H19C	109.5
C9—C8—C7	109.47 (18)	H19A—C19—H19C	109.5
O5—C9—C10	110.95 (19)	H19B—C19—H19C	109.5
O5—C9—C8	106.27 (17)	C10—C20—H20A	120.0
C10—C9—C8	112.45 (17)	C10—C20—H20B	120.0
O5—C9—H9A	109.0	H20A—C20—H20B	120.0
C10—C9—H9A	109.0	C21—O10—H10	109.5
C8—C9—H9A	109.0	O10—C21—H21A	109.5
C20—C10—C9	120.0 (2)	O10—C21—H21B	109.5
C20—C10—C11	122.6 (2)	H21A—C21—H21B	109.5
C9—C10—C11	117.39 (18)	O10—C21—H21C	109.5
O6—C11—C10	113.25 (17)	H21A—C21—H21C	109.5
O6—C11—C12	103.16 (17)	H21B—C21—H21C	109.5
C10—C11—C12	111.51 (18)	H1W1—O1W—H2W1	105.9
O6—C11—C16	108.23 (17)	H1W2—O2W—H2W2	108.4

C15—C1—C2—C3	148.4 (2)	C20—C10—C11—O6	27.0 (3)
C6—C1—C2—C3	19.9 (3)	C9—C10—C11—O6	−155.1 (2)
C15—C1—C2—C18	−35.2 (3)	C20—C10—C11—C12	−88.9 (3)
C6—C1—C2—C18	−163.7 (2)	C9—C10—C11—C12	89.0 (2)
C18—C2—C3—C4	−176.8 (2)	C20—C10—C11—C16	148.1 (2)
C1—C2—C3—C4	−0.5 (4)	C9—C10—C11—C16	−34.0 (3)
C2—C3—C4—O1	−168.7 (2)	O6—C11—C12—O7	−59.4 (2)
C2—C3—C4—C5	13.3 (3)	C10—C11—C12—O7	62.5 (2)
O1—C4—C5—O2	13.0 (3)	C16—C11—C12—O7	−174.96 (17)
C3—C4—C5—O2	−168.9 (2)	O6—C11—C12—C13	60.3 (2)
O1—C4—C5—C6	137.2 (2)	C10—C11—C12—C13	−177.82 (18)
C3—C4—C5—C6	−44.8 (3)	C16—C11—C12—C13	−55.3 (2)
O2—C5—C6—C19	63.6 (2)	C14—O9—C13—O8	166.4 (2)
C4—C5—C6—C19	−59.9 (2)	C14—O9—C13—C12	−16.6 (3)
O2—C5—C6—C1	−176.83 (19)	O7—C12—C13—O8	−27.5 (3)
C4—C5—C6—C1	59.7 (2)	C11—C12—C13—O8	−150.6 (2)
O2—C5—C6—C7	−62.8 (2)	O7—C12—C13—O9	155.59 (19)
C4—C5—C6—C7	173.71 (18)	C11—C12—C13—O9	32.5 (3)
C2—C1—C6—C5	−48.1 (2)	C13—O9—C14—C15	147.4 (2)
C15—C1—C6—C5	−178.84 (18)	C13—O9—C14—C16	22.0 (3)
C2—C1—C6—C19	69.6 (2)	O9—C14—C15—C1	−73.9 (2)
C15—C1—C6—C19	−61.1 (2)	C16—C14—C15—C1	50.4 (3)
C2—C1—C6—C7	−164.58 (18)	C2—C1—C15—C14	161.25 (19)
C15—C1—C6—C7	64.7 (2)	C6—C1—C15—C14	−67.7 (2)
C5—C6—C7—C8	83.5 (2)	O9—C14—C16—C17	−159.36 (18)
C19—C6—C7—C8	−39.2 (3)	C15—C14—C16—C17	81.6 (2)
C1—C6—C7—C8	−162.86 (18)	O9—C14—C16—C11	−42.3 (2)
C5—C6—C7—C16	−161.04 (18)	C15—C14—C16—C11	−161.36 (18)
C19—C6—C7—C16	76.2 (2)	O9—C14—C16—C7	84.8 (2)
C1—C6—C7—C16	−47.4 (2)	C15—C14—C16—C7	−34.2 (3)
C17—O4—C8—O3	154.14 (17)	O6—C11—C16—C14	−51.0 (2)
C17—O4—C8—C9	−89.8 (2)	C10—C11—C16—C14	−175.06 (18)
C17—O4—C8—C7	27.2 (2)	C12—C11—C16—C14	61.4 (2)
C16—C7—C8—O3	−161.90 (19)	O6—C11—C16—C17	67.6 (2)
C6—C7—C8—O3	−36.9 (3)	C10—C11—C16—C17	−56.5 (2)
C16—C7—C8—O4	−42.4 (2)	C12—C11—C16—C17	179.97 (17)
C6—C7—C8—O4	82.6 (2)	O6—C11—C16—C7	179.46 (17)
C16—C7—C8—C9	73.4 (2)	C10—C11—C16—C7	55.4 (2)
C6—C7—C8—C9	−161.50 (18)	C12—C11—C16—C7	−68.2 (2)
O3—C8—C9—O5	−67.8 (2)	C8—C7—C16—C14	161.50 (19)
O4—C8—C9—O5	176.98 (16)	C6—C7—C16—C14	33.8 (3)
C7—C8—C9—O5	62.6 (2)	C8—C7—C16—C17	41.6 (2)
O3—C8—C9—C10	170.59 (18)	C6—C7—C16—C17	−86.1 (2)
O4—C8—C9—C10	55.4 (2)	C8—C7—C16—C11	−73.2 (2)
C7—C8—C9—C10	−59.0 (2)	C6—C7—C16—C11	159.07 (18)
O5—C9—C10—C20	95.7 (3)	C8—O4—C17—C16	1.0 (2)
C8—C9—C10—C20	−145.4 (2)	C14—C16—C17—O4	−152.40 (18)
O5—C9—C10—C11	−82.2 (2)	C11—C16—C17—O4	89.98 (19)
C8—C9—C10—C11	36.6 (3)	C7—C16—C17—O4	−28.1 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1W—H1W1···O4ⁱ	0.88	1.94	2.810 (2)	169
O2—H2···O2Wⁱⁱ	0.82	1.85	2.656 (3)	169
O1W—H2W1···O3ⁱⁱⁱ	0.84	2.06	2.873 (3)	163
O3—H3···O2	0.82	1.71	2.525 (2)	171
O2W—H1W2···O8	0.95	2.03	2.950 (3)	164
O2W—H2W2···O10	0.85	1.91	2.760 (3)	179
O5—H5···O3^iv	0.82	1.99	2.805 (2)	172
O6—H6···O9^v	0.82	2.14	2.848 (2)	144
O7—H7···O1W^vi	0.82	1.84	2.653 (3)	171
O10—H10···O7^vii	0.82	2.29	3.011 (3)	147
O10—H10···O8^vii	0.82	2.23	2.911 (3)	140
C1—H1A···O9	0.98	2.48	2.936 (3)	108
C1—H1A···O1ⁱⁱⁱ	0.98	2.56	3.507 (3)	162
C7—H7A···O5	0.98	2.38	2.856 (3)	109
C12—H12A···O1ⁱⁱⁱ	0.98	2.47	3.168 (3)	128
C17—H17A···O10^v	0.97	2.60	3.428 (3)	144
C17—H17B···O6	0.97	2.50	2.929 (3)	107
C19—H19B···O2	0.96	2.56	2.957 (3)	105

Symmetry codes: (i) x+1, y+1, z; (ii) x−1/2, −y+1/2, −z+2; (iii) x+1/2, −y+1/2, −z+2; (iv) x+1/2, −y−1/2, −z+2; (v) −x+1, y−1/2, −z+3/2; (vi) x, y−1, z; (vii) −x+2, y+1/2, −z+3/2.

Experimental details

Crystal data
Chemical formula	C₂₀H₂₄O₉·CH₄O·2H₂O
M_r	476.47
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	100
a, b, c (Å)	9.1817 (1), 10.7806 (2), 21.7817 (3)
V (Å³)	2156.04 (6)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.12
Crystal size (mm)	0.43 × 0.28 × 0.11

Data collection
Diffractometer	Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2005)
T_min, T_max	0.950, 0.987
No. of measured, independent and observed [I > 2σ(I)] reflections	27636, 3577, 3352
R_int	0.033
(sin θ/λ)_max (Å⁻¹)	0.706

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.127, 1.09
No. of reflections	3577
No. of parameters	307
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	1.08, −0.46

Computer programs: APEX2 (Bruker, 2005), SAINT (Bruker, 2005), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1W—H1W1···O4ⁱ	0.8800	1.9400	2.810 (2)	169.00
O2—H2···O2Wⁱⁱ	0.8200	1.8500	2.656 (3)	169.00
O1W—H2W1···O3ⁱⁱⁱ	0.8400	2.0600	2.873 (3)	163.00
O3—H3···O2	0.8200	1.7100	2.525 (2)	171.00
O2W—H1W2···O8	0.9500	2.0300	2.950 (3)	164.00
O2W—H2W2···O10	0.8500	1.9100	2.760 (3)	179.00
O5—H5···O3^iv	0.8200	1.9900	2.805 (2)	172.00
O6—H6···O9^v	0.8200	2.1400	2.848 (2)	144.00
O7—H7···O1W^vi	0.8200	1.8400	2.653 (3)	171.00
O10—H10···O7^vii	0.8200	2.2900	3.011 (3)	147.00
O10—H10···O8^vii	0.8200	2.2300	2.911 (3)	140.00
C1—H1A···O9	0.9800	2.4800	2.936 (3)	108.00
C1—H1A···O1ⁱⁱⁱ	0.9800	2.5600	3.507 (3)	162.00
C7—H7A···O5	0.9800	2.3800	2.856 (3)	109.00
C12—H12A···O1ⁱⁱⁱ	0.9800	2.4700	3.168 (3)	128.00
C17—H17A···O10^v	0.9700	2.6000	3.428 (3)	144.00
C17—H17B···O6	0.9700	2.5000	2.929 (3)	107.00
C19—H19B···O2	0.9600	2.5600	2.957 (3)	105.00

Footnotes

‡Additional correspondence author: e-mail: klchan@usm.my.

Acknowledgements

KLC and CHT thank Universiti Sains Malaysia for a Research University grant No. 1001/PFARMASI/813006. HKF and SCT thank Universiti Sains Malaysia for the Research University Golden Goose grant No. 1001/PFIZIK/811012. YCS thanks Universiti Sains Malaysia for a studentship award.

References

Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19. CrossRef Web of Science Google Scholar
Ang, H. H., Chan, K. L. & Mak, J. W. (1995). Planta Med. 61, 177–178. CrossRef CAS PubMed Web of Science Google Scholar
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573. CrossRef CAS Web of Science Google Scholar
Bruker (2005). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Chan, K.-L., Choo, C.-Y., Abdullah, N. R. & Ismail, Z. (2004). J. Ethnopharmacol. 92, 223–227. Web of Science CrossRef PubMed CAS Google Scholar
Chan, K. L., Iitaka, Y., Noguchi, H., Sugiyama, H., Saito, I. & Sankawa, U. (1992). Phytochemistry, 31, 4295–4298. CSD CrossRef CAS Web of Science Google Scholar
Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, 105–107. CrossRef CAS Web of Science IUCr Journals Google Scholar
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358. CrossRef CAS Web of Science Google Scholar
Itokawa, H., Kishi, E., Morita, H. & Takeya, K. (1992). Chem. Pharm. Bull. 40, 1053–1055. CrossRef CAS Google Scholar
Itokawa, H., Qin, X. R., Morita, H., Takeya, K. & Iitaka, Y. (1993). Chem. Pharm. Bull. 41, 403–405. CrossRef CAS Google Scholar
Kardono, L. B. S., Angerhofer, C. K., Tsauri, S., Padmawinata, K., Pezzuto, J. M. & Kinghorn, A. D. (1991). J. Nat. Prod. 54, 1360–1367. CrossRef PubMed CAS Web of Science Google Scholar
Morita, H., Kishi, E., Takeya, K. & Itokawa, H. (1992). Phytochemistry, 31, 3993–3995. CrossRef CAS Web of Science Google Scholar
Morita, H., Kishi, E., Takeya, K., Itokawa, H. & Iitaka, Y. (1993). Phytochemistry, 34, 765–771. CSD CrossRef CAS Web of Science Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Tada, H., Yasuda, F., Otani, K., Doteuchi, M., Ishihara, Y. & Shiro, M. (1991). Eur. J. Med. Chem. 26, 345–349. CrossRef CAS Web of Science Google Scholar

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