Epibisde­hydro­neotuberostemonine J

Jin, L.; Zhang, R.-R.; Tian, H.-Y.; But, P.P.-H.; Jiang, R.-W.

doi:10.1107/S1600536813021077

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 69| Part 9| September 2013| Pages o1369-o1370

doi:10.1107/S1600536813021077

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Epibisdehydroneotuberostemonine J

Lu Jin,^a Rong-Rong Zhang,^a Hai-Yan Tian,^a Paul Pui-Hay But ^b and Ren-Wang Jiang ^a ^*

^aGuangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, People's Republic of China, and ^bSchool of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, People's Republic of China
^*Correspondence e-mail: trwjiang@jnu.edu.cn

(Received 4 July 2013; accepted 29 July 2013; online 3 August 2013)

The title compound, C₂₂H₂₉NO₄, a stemona alkaloid, is composed of two lactone rings (A and E), a six-membered ring (B), a pyrrole ring (C) and a seven-membered ring (D). The five-membered rings A and E exhibit envelope conformations (C atoms as flaps) while ring C is planar. Ring B exhibits a twist-chair conformation due to fusion with pyrrole ring C while ring D adopts a chair conformation. The junction between rings A and B is cis. In the crystal, weak C—H⋯O interactions involving the two carbonyl groups, a methylene and a methyl group give rise to a three-dimensional network.

Related literature

For general background to the structures and biological activity of stemona alkaloids, see: Pilli et al. (2010 ). For the antitussive activity of epibisdehydroneotuberostemonine J and other stemona alkaloids, see: Chung et al. (2003 ); Xu et al. (2010 ). For other properties of and studies on Stemona alkaloids, see: Chung et al. (2003); Frankowski et al. (2008 , 2011 ); Jiang et al. (2006 ); Zhang et al. (2011 ). For an absolute structure reference, see: Jiang et al. (2010 ). For related isomers, see: Pham et al. (2002 ).

Experimental

Crystal data

C₂₂H₂₉NO₄
M_r = 371.46
Monoclinic, P 2₁
a = 6.3596 (19) Å
b = 18.495 (3) Å
c = 8.3875 (15) Å
β = 92.521 (18)°
V = 985.6 (4) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 291 K
0.43 × 0.28 × 0.20 mm

Data collection

Bruker SMART 1000 CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2004 ) T_min = 0.831, T_max = 1.000
2449 measured reflections
1914 independent reflections
1383 reflections with I > 2σ(I)
R_int = 0.022

Refinement

R[F² > 2σ(F²)] = 0.045
wR(F²) = 0.093
S = 1.05
1914 reflections
245 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.13 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5A⋯O2ⁱ	0.97	2.60	3.531 (4)	161
C5—H5B⋯O4ⁱⁱ	0.97	2.66	3.595 (3)	162
C22—H22B⋯O4ⁱⁱⁱ	0.96	2.63	3.496 (4)	150
Symmetry codes: (i) $[-x+1, y-{\script{1\over 2}}, -z]$ ; (ii) x, y, z+1; (iii) x-1, y, z.

Data collection: SMART (Bruker, 1998 ); cell refinement: SMART and SAINT (Bruker, 1998); data reduction: SAINT and XPREP (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536813021077/zl2558sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813021077/zl2558Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813021077/zl2558Isup3.cml

checkCIF report

Comment top

Radix Stemonae extracts derived from the root of Stemona tuberosa (Stemonaceae family) are often used as an antitussive drug to treat respiratory disorders. The alkaloids were found to be the major components responsible for the antitussive activity (Xu et al., 2010). The intriguing structures and pharmacological activities of this fascinating class of compounds have attracted considerable attention (Pilli et al., 2010), and a number of total syntheses (Frankowski et al., 2008), structural modifications (Frankowski et al., 2011) and phytochemical studies (Jiang et al., 2006, Zhang et al., 2011) on new Stemona alkaloids have appeared in recent years.

The title compound C₂₂H₂₉N₁O₄ (Fig. 1) is a Stemona alkaloid. It was first isolated from the roots of Stemona tuberosa ten years ago (Chung et al., 2003) and found to show antitussive activity (Chung et al., 2003); however, its crystal structure had not been reported.

During our on-going search for antitussive natural products, epibisdehydroneotuberostemonine J was isolated again from Stemona tuberosa. It is an isomer of bisdehydroneotuberostemonine (Pham et al., 2002) at C-9 and C-18. The molecule is composed of two lactone ring (A and E), a six-membered ring (B), a pyrrole ring (C) and a seven-membered ring (D). The five-membered rings A and E exhibit envelope conformations while ring C is planar. The six-membered ring B exhibits a twist chair conformation due to fusion with the pyrrole ring C. The seven-membered ring D adopts a chair conformation, in which the atoms C-5, C-6, C-8, C-9 form a plane with a mean deviation of 0.043 (2) Å, and the atoms C-9 A, N-4 and C-7 displaced by -1.070 (3), -1.040 (2) and 0.662 (4) Å from the plane, respectively.

Weak intermolecular C–H···O interactions (Table 1) involving the two carbonyl groups (O-2 and O-4), a methylene (C-5) and a methyl group (C-22) give a three-dimensional structure.

Related literature top

For general background to the structures and biological activity of stemona alkaloids, see: Pilli et al. (2010). For the antitussive activity of epibisdehydroneotuberostemonine J and other stemona alkaloids, see: Chung et al. (2003); Xu et al. (2010). For other properties of and studies on Stemona alkaloids, see: Chung et al. (2003); Frankowski et al. (2008, 2011); Jiang et al. (2006); Zhang et al. (2011). For an absolute structure reference, see: Jiang et al. (2010). For related isomers, see: Pham et al. (2002).

Experimental top

A dry ground herbal sample of Radix Stemonae (5.0 kg) was suspended in 95% EtOH (10 L) and heated for two hours to reflux of the solvent. After filtration, the solvent was evaporated under reduced pressure. The residue was acidified with 4% HCl (400 ml) and filtered with Whatman filter papers, then the filtrate (acidic aqueous solution) was washed with diethyl ether (500 ml). The H₂O layer was basified to pH = 9 with aqueous ammonia (35%) and then extracted with Et₂O (500 ml). The Et₂O layer was evaporated to afford the crude alkaloids (15 g), which were subjected to column chromatography over silica gel, and eluted with chloroform: methanol: amonia (98: 2: 0.05) to yield ten fractions. Fraction 3 (2 g), a low polar fraction with an Rf value larger than 0.7 on a normal phase TLC plate (mobile phase cyclohexane: ethyl acetate 1: 1), was subjected to a second separation by silica-gel chromatography with cyclohexane: ethyl acetate (7: 3) as the eluent to yield the title compound (180 mg, colorless powder, Rf = 0.76 at the same TLC condition as bulk fraction 3), which was identified by comparision of the physical and spectroscopic data with the literature (Chung et al., 2003). Colorless crystals suitable for single crystal diffraction were obtained from a mixture of cyclohexane: ethyl acetate at room temperature.

Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: SMART and SAINT (Bruker, 1998); data reduction: SAINT and XPREP (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of the title compound showing 30% probability displacement ellipsoids and the atom-numbering scheme.
	Fig. 2. Packing diagram viewed down the a axis.

(9R,10R,11S,14S,15R)-3-[(2S,5S)-4,5-dimethyloxolan-2-yl]-10-ethyl-14-methyl-12-oxa-4-azatetracyclo[7.6.1.0^4,16.0^11,15]hexadeca-1(16),2-dien-13-one top

Crystal data top

C₂₂H₂₉NO₄	F(000) = 400
M_r = 371.46	D_x = 1.252 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
a = 6.3596 (19) Å	Cell parameters from 2449 reflections
b = 18.495 (3) Å	θ = 2.2–24.0°
c = 8.3875 (15) Å	µ = 0.09 mm⁻¹
β = 92.521 (18)°	T = 291 K
V = 985.6 (4) Å³	Prism, colorless
Z = 2	0.43 × 0.28 × 0.20 mm

Data collection top

Bruker SMART 1000 CCD diffractometer	1383 reflections with I > 2σ(I)
Radiation source: sealed tube	R_int = 0.022
ω scan	θ_max = 25.0°, θ_min = 2.2°
Absorption correction: multi-scan (SADABS; Sheldrick, 2004)	h = −1→7
T_min = 0.831, T_max = 1.000	k = −1→21
2449 measured reflections	l = −9→9
1914 independent reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.045	H-atom parameters constrained
wR(F²) = 0.093	w = 1/[σ²(F_o²) + (0.0368P)² + 0.0285P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max < 0.001
1914 reflections	Δρ_max = 0.13 e Å⁻³
245 parameters	Δρ_min = −0.13 e Å⁻³
1 restraint	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.013 (2)

Crystal data top

C₂₂H₂₉NO₄	V = 985.6 (4) Å³
M_r = 371.46	Z = 2
Monoclinic, P2₁	Mo Kα radiation
a = 6.3596 (19) Å	µ = 0.09 mm⁻¹
b = 18.495 (3) Å	T = 291 K
c = 8.3875 (15) Å	0.43 × 0.28 × 0.20 mm
β = 92.521 (18)°

Data collection top

Bruker SMART 1000 CCD diffractometer	1914 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 2004)	1383 reflections with I > 2σ(I)
T_min = 0.831, T_max = 1.000	R_int = 0.022
2449 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.045	1 restraint
wR(F²) = 0.093	H-atom parameters constrained
S = 1.05	Δρ_max = 0.13 e Å⁻³
1914 reflections	Δρ_min = −0.13 e Å⁻³
245 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
O1	0.5763 (4)	0.32620 (15)	0.2326 (4)	0.0552 (8)
O2	0.6531 (5)	0.36723 (17)	−0.0073 (4)	0.0716 (9)
O3	0.4293 (4)	0.02284 (15)	−0.1869 (3)	0.0472 (7)
O4	0.5576 (4)	−0.01361 (17)	−0.4150 (3)	0.0611 (9)
C1	0.2603 (6)	0.2093 (2)	0.1225 (5)	0.0451 (11)
C2	0.1727 (6)	0.1714 (2)	−0.0118 (5)	0.0469 (10)
H2A	0.0781	0.1903	−0.0886	0.056*
C3	0.2514 (6)	0.1021 (2)	−0.0095 (5)	0.0418 (10)
N4	0.3821 (5)	0.09614 (16)	0.1254 (4)	0.0404 (8)
C5	0.5164 (6)	0.0346 (2)	0.1696 (5)	0.0449 (10)
H5A	0.4792	−0.0063	0.1015	0.054*
H5B	0.4929	0.0208	0.2790	0.054*
C6	0.7464 (6)	0.0528 (2)	0.1536 (5)	0.0483 (11)
H6A	0.8247	0.0079	0.1468	0.058*
H6B	0.7611	0.0785	0.0540	0.058*
C7	0.8456 (6)	0.0977 (2)	0.2873 (5)	0.0505 (11)
H7A	0.9952	0.1014	0.2707	0.061*
H7B	0.8298	0.0720	0.3868	0.061*
C8	0.7586 (6)	0.1742 (2)	0.3066 (5)	0.0472 (10)
H8A	0.7729	0.2005	0.2076	0.057*
H8B	0.8419	0.1991	0.3892	0.057*
C9A	0.3875 (6)	0.1609 (2)	0.2037 (5)	0.0426 (10)
C9	0.5259 (6)	0.1751 (2)	0.3501 (4)	0.0440 (10)
H9A	0.5059	0.1348	0.4236	0.053*
C10	0.4468 (7)	0.2435 (2)	0.4320 (5)	0.0501 (11)
H10A	0.3150	0.2295	0.4798	0.060*
C11	0.3881 (7)	0.3036 (2)	0.3145 (5)	0.0557 (12)
H11A	0.3360	0.3449	0.3742	0.067*
C12	0.2296 (6)	0.2868 (2)	0.1766 (5)	0.0493 (11)
H12A	0.0855	0.2939	0.2102	0.059*
C13	0.2864 (7)	0.3445 (2)	0.0563 (5)	0.0561 (12)
H13A	0.2310	0.3903	0.0954	0.067*
C14	0.5207 (8)	0.3479 (2)	0.0821 (6)	0.0556 (12)
C15	0.2115 (7)	0.3382 (3)	−0.1162 (6)	0.0708 (14)
H15A	0.2599	0.3792	−0.1745	0.106*
H15B	0.0605	0.3368	−0.1232	0.106*
H15C	0.2665	0.2947	−0.1608	0.106*
C16	0.5885 (7)	0.2711 (3)	0.5694 (5)	0.0615 (13)
H16A	0.5235	0.3133	0.6154	0.074*
H16B	0.7215	0.2863	0.5279	0.074*
C17	0.6320 (8)	0.2152 (3)	0.7012 (6)	0.0754 (15)
H17A	0.7226	0.2360	0.7836	0.113*
H17B	0.6990	0.1736	0.6573	0.113*
H17C	0.5016	0.2009	0.7454	0.113*
C18	0.2231 (5)	0.0417 (2)	−0.1246 (5)	0.0438 (10)
H18A	0.1681	−0.0004	−0.0688	0.053*
C19	0.0829 (7)	0.0565 (2)	−0.2721 (5)	0.0574 (12)
H19A	−0.0591	0.0393	−0.2578	0.069*
H19B	0.0778	0.1078	−0.2957	0.069*
C20	0.1851 (6)	0.0151 (3)	−0.4045 (5)	0.0504 (11)
H20A	0.1825	0.0449	−0.5011	0.060*
C21	0.4088 (6)	0.0065 (2)	−0.3421 (5)	0.0457 (10)
C22	0.0893 (7)	−0.0577 (3)	−0.4437 (7)	0.0806 (16)
H22A	0.1641	−0.0799	−0.5278	0.121*
H22B	−0.0558	−0.0516	−0.4776	0.121*
H22C	0.0985	−0.0879	−0.3507	0.121*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0521 (19)	0.0380 (17)	0.076 (2)	−0.0075 (15)	0.0086 (17)	0.0000 (16)
O2	0.072 (2)	0.051 (2)	0.093 (2)	−0.0096 (18)	0.0255 (19)	0.0111 (19)
O3	0.0362 (15)	0.0522 (17)	0.0528 (17)	0.0054 (14)	−0.0032 (13)	−0.0032 (16)
O4	0.0454 (18)	0.079 (2)	0.0597 (18)	0.0066 (18)	0.0107 (16)	0.0065 (18)
C1	0.038 (2)	0.036 (2)	0.062 (3)	−0.001 (2)	0.009 (2)	0.002 (2)
C2	0.032 (2)	0.041 (2)	0.068 (3)	0.003 (2)	−0.001 (2)	0.005 (2)
C3	0.034 (2)	0.034 (2)	0.057 (3)	−0.0011 (19)	0.002 (2)	−0.001 (2)
N4	0.0352 (17)	0.0295 (18)	0.056 (2)	0.0002 (16)	0.0012 (16)	−0.0011 (17)
C5	0.047 (2)	0.036 (2)	0.052 (2)	0.005 (2)	−0.001 (2)	0.001 (2)
C6	0.042 (2)	0.042 (2)	0.061 (3)	0.006 (2)	−0.002 (2)	0.000 (2)
C7	0.038 (2)	0.053 (3)	0.060 (3)	0.002 (2)	0.002 (2)	0.008 (2)
C8	0.038 (2)	0.046 (2)	0.058 (3)	−0.008 (2)	0.0031 (19)	−0.004 (2)
C9A	0.035 (2)	0.036 (2)	0.058 (3)	−0.0071 (19)	0.006 (2)	−0.002 (2)
C9	0.044 (2)	0.036 (2)	0.052 (2)	−0.007 (2)	0.0098 (19)	−0.005 (2)
C10	0.048 (3)	0.037 (2)	0.066 (3)	−0.008 (2)	0.013 (2)	−0.004 (2)
C11	0.054 (3)	0.040 (3)	0.074 (3)	0.002 (2)	0.018 (3)	−0.015 (2)
C12	0.041 (2)	0.038 (2)	0.070 (3)	0.004 (2)	0.010 (2)	0.001 (2)
C13	0.059 (3)	0.033 (2)	0.076 (3)	0.009 (2)	0.009 (3)	0.002 (2)
C14	0.071 (3)	0.024 (2)	0.074 (3)	−0.004 (2)	0.015 (3)	0.001 (2)
C15	0.074 (3)	0.047 (3)	0.092 (4)	0.006 (3)	0.009 (3)	0.008 (3)
C16	0.072 (3)	0.053 (3)	0.061 (3)	−0.009 (3)	0.010 (3)	−0.012 (3)
C17	0.083 (4)	0.077 (4)	0.066 (3)	0.000 (3)	0.003 (3)	−0.008 (3)
C18	0.029 (2)	0.044 (3)	0.059 (2)	−0.001 (2)	0.0064 (19)	−0.006 (2)
C19	0.042 (2)	0.054 (3)	0.076 (3)	0.008 (2)	−0.012 (2)	−0.008 (3)
C20	0.045 (2)	0.051 (3)	0.055 (2)	0.008 (2)	−0.008 (2)	0.004 (2)
C21	0.042 (2)	0.043 (2)	0.052 (3)	0.002 (2)	−0.001 (2)	0.007 (2)
C22	0.055 (3)	0.062 (3)	0.123 (4)	0.008 (3)	−0.020 (3)	−0.022 (3)

Geometric parameters (Å, º) top

O1—C14	1.356 (5)	C10—C16	1.519 (5)
O1—C11	1.467 (5)	C10—C11	1.520 (6)
O2—C14	1.207 (5)	C10—H10A	0.9800
O3—C21	1.337 (4)	C11—C12	1.533 (6)
O3—C18	1.475 (4)	C11—H11A	0.9800
O4—C21	1.207 (4)	C12—C13	1.523 (6)
C1—C9A	1.368 (5)	C12—H12A	0.9800
C1—C2	1.420 (5)	C13—C14	1.498 (6)
C1—C12	1.518 (6)	C13—C15	1.507 (6)
C2—C3	1.375 (5)	C13—H13A	0.9800
C2—H2A	0.9300	C15—H15A	0.9600
C3—N4	1.378 (5)	C15—H15B	0.9600
C3—C18	1.483 (5)	C15—H15C	0.9600
N4—C9A	1.366 (5)	C16—C17	1.530 (6)
N4—C5	1.462 (5)	C16—H16A	0.9700
C5—C6	1.513 (5)	C16—H16B	0.9700
C5—H5A	0.9700	C17—H17A	0.9600
C5—H5B	0.9700	C17—H17B	0.9600
C6—C7	1.512 (5)	C17—H17C	0.9600
C6—H6A	0.9700	C18—C19	1.518 (5)
C6—H6B	0.9700	C18—H18A	0.9800
C7—C8	1.529 (6)	C19—C20	1.518 (6)
C7—H7A	0.9700	C19—H19A	0.9700
C7—H7B	0.9700	C19—H19B	0.9700
C8—C9	1.540 (5)	C20—C21	1.503 (5)
C8—H8A	0.9700	C20—C22	1.508 (6)
C8—H8B	0.9700	C20—H20A	0.9800
C9A—C9	1.502 (5)	C22—H22A	0.9600
C9—C10	1.534 (6)	C22—H22B	0.9600
C9—H9A	0.9800	C22—H22C	0.9600

C14—O1—C11	109.6 (3)	C1—C12—C11	109.1 (3)
C21—O3—C18	110.4 (3)	C13—C12—C11	101.0 (3)
C9A—C1—C2	106.0 (3)	C1—C12—H12A	110.3
C9A—C1—C12	123.3 (4)	C13—C12—H12A	110.3
C2—C1—C12	130.7 (4)	C11—C12—H12A	110.3
C3—C2—C1	108.6 (4)	C14—C13—C15	114.4 (4)
C3—C2—H2A	125.7	C14—C13—C12	101.3 (4)
C1—C2—H2A	125.7	C15—C13—C12	120.5 (4)
C2—C3—N4	107.0 (4)	C14—C13—H13A	106.6
C2—C3—C18	131.3 (4)	C15—C13—H13A	106.6
N4—C3—C18	121.7 (3)	C12—C13—H13A	106.6
C9A—N4—C3	109.1 (3)	O2—C14—O1	120.4 (4)
C9A—N4—C5	124.0 (3)	O2—C14—C13	129.8 (5)
C3—N4—C5	126.5 (3)	O1—C14—C13	109.9 (4)
N4—C5—C6	111.1 (3)	C13—C15—H15A	109.5
N4—C5—H5A	109.4	C13—C15—H15B	109.5
C6—C5—H5A	109.4	H15A—C15—H15B	109.5
N4—C5—H5B	109.4	C13—C15—H15C	109.5
C6—C5—H5B	109.4	H15A—C15—H15C	109.5
H5A—C5—H5B	108.0	H15B—C15—H15C	109.5
C7—C6—C5	115.5 (3)	C10—C16—C17	113.8 (4)
C7—C6—H6A	108.4	C10—C16—H16A	108.8
C5—C6—H6A	108.4	C17—C16—H16A	108.8
C7—C6—H6B	108.4	C10—C16—H16B	108.8
C5—C6—H6B	108.4	C17—C16—H16B	108.8
H6A—C6—H6B	107.5	H16A—C16—H16B	107.7
C6—C7—C8	116.5 (3)	C16—C17—H17A	109.5
C6—C7—H7A	108.2	C16—C17—H17B	109.5
C8—C7—H7A	108.2	H17A—C17—H17B	109.5
C6—C7—H7B	108.2	C16—C17—H17C	109.5
C8—C7—H7B	108.2	H17A—C17—H17C	109.5
H7A—C7—H7B	107.3	H17B—C17—H17C	109.5
C7—C8—C9	113.1 (3)	O3—C18—C3	108.9 (3)
C7—C8—H8A	109.0	O3—C18—C19	104.7 (3)
C9—C8—H8A	109.0	C3—C18—C19	116.4 (3)
C7—C8—H8B	109.0	O3—C18—H18A	108.9
C9—C8—H8B	109.0	C3—C18—H18A	108.9
H8A—C8—H8B	107.8	C19—C18—H18A	108.9
N4—C9A—C1	109.4 (3)	C20—C19—C18	104.5 (3)
N4—C9A—C9	123.3 (3)	C20—C19—H19A	110.9
C1—C9A—C9	127.2 (4)	C18—C19—H19A	110.9
C9A—C9—C10	108.6 (3)	C20—C19—H19B	110.9
C9A—C9—C8	109.8 (3)	C18—C19—H19B	110.9
C10—C9—C8	116.9 (3)	H19A—C19—H19B	108.9
C9A—C9—H9A	107.0	C21—C20—C22	110.4 (4)
C10—C9—H9A	107.0	C21—C20—C19	103.2 (3)
C8—C9—H9A	107.0	C22—C20—C19	115.3 (4)
C16—C10—C11	111.5 (3)	C21—C20—H20A	109.2
C16—C10—C9	114.9 (4)	C22—C20—H20A	109.2
C11—C10—C9	112.8 (3)	C19—C20—H20A	109.2
C16—C10—H10A	105.6	O4—C21—O3	121.2 (3)
C11—C10—H10A	105.6	O4—C21—C20	127.4 (4)
C9—C10—H10A	105.6	O3—C21—C20	111.4 (4)
O1—C11—C10	109.3 (3)	C20—C22—H22A	109.5
O1—C11—C12	103.1 (3)	C20—C22—H22B	109.5
C10—C11—C12	118.4 (3)	H22A—C22—H22B	109.5
O1—C11—H11A	108.5	C20—C22—H22C	109.5
C10—C11—H11A	108.5	H22A—C22—H22C	109.5
C12—C11—H11A	108.5	H22B—C22—H22C	109.5
C1—C12—C13	115.3 (3)

C9A—C1—C2—C3	−0.9 (5)	C9A—C1—C12—C13	122.1 (4)
C12—C1—C2—C3	179.3 (4)	C2—C1—C12—C13	−58.1 (6)
C1—C2—C3—N4	1.2 (4)	C9A—C1—C12—C11	9.3 (5)
C1—C2—C3—C18	−175.9 (4)	C2—C1—C12—C11	−170.9 (4)
C2—C3—N4—C9A	−1.1 (4)	O1—C11—C12—C1	86.1 (4)
C18—C3—N4—C9A	176.4 (3)	C10—C11—C12—C1	−34.7 (5)
C2—C3—N4—C5	−173.7 (3)	O1—C11—C12—C13	−35.8 (4)
C18—C3—N4—C5	3.8 (6)	C10—C11—C12—C13	−156.5 (4)
C9A—N4—C5—C6	−62.4 (5)	C1—C12—C13—C14	−80.9 (4)
C3—N4—C5—C6	109.1 (4)	C11—C12—C13—C14	36.6 (4)
N4—C5—C6—C7	78.0 (4)	C1—C12—C13—C15	46.5 (5)
C5—C6—C7—C8	−64.2 (5)	C11—C12—C13—C15	163.9 (4)
C6—C7—C8—C9	63.6 (5)	C11—O1—C14—O2	−178.3 (4)
C3—N4—C9A—C1	0.5 (4)	C11—O1—C14—C13	2.8 (4)
C5—N4—C9A—C1	173.3 (3)	C15—C13—C14—O2	24.3 (7)
C3—N4—C9A—C9	−175.8 (3)	C12—C13—C14—O2	155.6 (4)
C5—N4—C9A—C9	−3.0 (6)	C15—C13—C14—O1	−157.0 (3)
C2—C1—C9A—N4	0.2 (4)	C12—C13—C14—O1	−25.7 (4)
C12—C1—C9A—N4	−180.0 (4)	C11—C10—C16—C17	173.3 (4)
C2—C1—C9A—C9	176.4 (4)	C9—C10—C16—C17	−56.7 (5)
C12—C1—C9A—C9	−3.8 (6)	C21—O3—C18—C3	−141.6 (3)
N4—C9A—C9—C10	−163.9 (4)	C21—O3—C18—C19	−16.5 (4)
C1—C9A—C9—C10	20.4 (6)	C2—C3—C18—O3	117.6 (4)
N4—C9A—C9—C8	67.1 (5)	N4—C3—C18—O3	−59.2 (4)
C1—C9A—C9—C8	−108.6 (5)	C2—C3—C18—C19	−0.4 (6)
C7—C8—C9—C9A	−78.1 (4)	N4—C3—C18—C19	−177.2 (3)
C7—C8—C9—C10	157.7 (4)	O3—C18—C19—C20	23.7 (4)
C9A—C9—C10—C16	−171.9 (3)	C3—C18—C19—C20	144.0 (3)
C8—C9—C10—C16	−47.0 (5)	C18—C19—C20—C21	−22.1 (4)
C9A—C9—C10—C11	−42.5 (4)	C18—C19—C20—C22	98.3 (4)
C8—C9—C10—C11	82.3 (5)	C18—O3—C21—O4	−176.7 (4)
C14—O1—C11—C10	148.1 (3)	C18—O3—C21—C20	2.1 (5)
C14—O1—C11—C12	21.3 (4)	C22—C20—C21—O4	68.0 (6)
C16—C10—C11—O1	67.9 (4)	C19—C20—C21—O4	−168.2 (4)
C9—C10—C11—O1	−63.2 (4)	C22—C20—C21—O3	−110.7 (4)
C16—C10—C11—C12	−174.5 (3)	C19—C20—C21—O3	13.1 (5)
C9—C10—C11—C12	54.4 (5)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5A···O2ⁱ	0.97	2.60	3.531 (4)	161
C5—H5B···O4ⁱⁱ	0.97	2.66	3.595 (3)	162
C22—H22B···O4ⁱⁱⁱ	0.96	2.63	3.496 (4)	150

Symmetry codes: (i) −x+1, y−1/2, −z; (ii) x, y, z+1; (iii) x−1, y, z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5A···O2ⁱ	0.970	2.598	3.531 (4)	161.4
C5—H5B···O4ⁱⁱ	0.970	2.659	3.595 (3)	162.2
C22—H22B···O4ⁱⁱⁱ	0.960	2.632	3.496 (4)	150.0

Symmetry codes: (i) −x+1, y−1/2, −z; (ii) x, y, z+1; (iii) x−1, y, z.

Acknowledgements

This work was supported by a grant of the Guangdong High Level Talent Scheme (RWJ) from Guangdong province and the Fundamental Research Funds for the Cental Universities (21612603) from the Ministry of Education, P. R. of China.

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