Conessine isolated from Holarrhena floribunda

The title compound, C₂₄H₄₀N₂, has been isolated from Holarrhena floribunda G. Don. (Apocynaceae). The compound has a penta­cyclic steroidal nucleus; the ring junctions share the same stereochemistry reported for this class of compounds. Of the three six-membered rings, rings A and C adopt a chair-like and ring B forms a half-chair-like conformation. The cyclo­pentane ring D shows a half-chair conformation and the methyl­pyrrolidine ring E adopts an envelope conformation. The dimethyl­amino substituent in ring A is equatorially oriented.

Key indicators

• Single-crystal X-ray study
• T = 173 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.048
• wR factor = 0.119
• Data-to-parameter ratio = 12.3

checkCIF/PLATON results

No syntax errors found



Alert level C
STRVA01_ALERT_4_C           Flack test results are meaningless.
           From the CIF: _refine_ls_abs_structure_Flack    0.000
           From the CIF: _refine_ls_abs_structure_Flack_su    4.000
PLAT032_ALERT_4_C Std. Uncertainty in Flack Parameter too High ...       4.00
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          1
              C24 H40 N2
PLAT850_ALERT_2_C Check Flack Parameter Exact Value 0.00 and su ..       4.00

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           28.30
           From the CIF: _reflns_number_total               2955
           Count of symmetry unique reflns         2954
           Completeness (_total/calc)            100.03%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         1
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C3     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C8     = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C9     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C10    = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C13    = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C14    = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C17    = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C18    = .          S

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

   9 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   5 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Holarrhena floribunda G. Don. (Apocynaceae) is a shrub to medium sized tree, up to 5–15 m in height that grows in central and West African savannah regions. It is commonly used in African folk medicines for the treatment of various ailments such as malaria, dysentery, skin infections and venereal diseases (Berhaut, 1971). Pharmacological investigations of H. floribunda revealed antimalarial (Fotie et al., 2006) and antimicrobial (Chukwurah, 1997) activities. Previous phytochemical studies resulted in the isolation of steroidal alkaloids (Leboeuf et al., 1969) and lupeol long-chain fatty acid esters (Fotie et al., 2006). Major compounds found in Holarrhena floribunda are steroidal alkaloids of two main chemical families: counanin and pregnen-5. Conessine, holarrhenine, holadienine, holamine, holaphylline, holaphyllamine and kurchicine are well known (Tamboura et al., 2005). Tetracyclic pyrrolidine C, which contains the key BCDE ring system of conessine (I), has four contiguous stereogenic centers, one of which is a quaternary carbon atom. In early reports, the synthesis of racemic steroidal alkaloids from racemic C was reported as an efficient pathway (Biao et al., 2004). No studies have been carried out on the alkaloids biosynthesized in the callus culture. However, previous studies have shown that tissue cultures of Holarrhena anridysenrerica produce several steroids and alkaloids, one of which was tentatively identified by thin- layer chromatography (TLC) as conessine (Bouillard et al., 1987). Recently, the antiplasmodial (Zirihi et al., 2005) activity of conessine (I), has been reported against the chloroquine-resistant strain FcB1 of Plasmodium falciparum. The antidiarrhoel properties (Kumar et al., 2007) of conessine were also studied. In this paper, we report the absolute structure and relative stereochemistry of title compound (I), isolated from the stem bark of H. floribunda.

The bond lengths and angles in the title compound (I) show normal values (Allen et al., 1987) and the pentacyclic steroidal nucleus has a trans/trans/cis conformations for B/C/D rings (Table 1). Among the cylohexane rings, rings A and C adopt chair-like conformation and ring B has half chair-like conformation, with puckering amplitude Q= 0.492 (2)°, θ= 51.4 (2)° and φ= 231.8 (15)° (Cremer & Pople, 1975). The half chair conformation in ring B is attributed to the presence of a double bond between C-5 and C-6 atoms. The cyclopentane ring D shows half chair conformation and a cis fused ring E of methylpyrrolidine appeared as an envelop [φ= 25.8 (3)°]. The equatorially oriented dimethylamino substitutent at C-3 is making an angle 77.5 (13)° on the Cremer and Pople plane (Cremer & Pople, 1975). The methyl substituent at C-18 is also attached equatorailly to ring E of the molecule (I) by having an angle 72.9 (3) on Cremer & Pople plane (Cremer & Pople, 1975). The N, N-dimethyl substitutent at C-3, methyl substituents at C-10 and C-18 are β-oriented in the title compound (I). The sum of the bonds around N1 [337.8°] and N2 [330.1°] are indicative of their sp³ character.

Related literature

For related literature, see: Allen et al. (1987); Berhaut (1971); Biao & Min (2004); Bouillard et al. (1987); Chukwurah (1997); Cremer & Pople (1975); Fotie et al. (2006); Kumar et al. (2007); Leboeuf et al. (1969); Tamboura et al. (2005); Zirihi et al. (2005); Schlittler et al. (1949).

S2. Experimental

Powdered stem barks of Holarrhena floribunda (5.4 kg) were soaked and extracted with MeOH for four days. The combined methanol extracts were dried under vacuum to afford a green gum (224 g). This methanolic extract was percolated with very dilute hydrochloric acid (5%). The liquor was made alkaline with ammonia (pH = 9) and extracted with ethyl acetate. The ethyl acetate extract was subjected to column chromatography, using hexane-ethyl acetate mixture of increasing polarity. The less polar fraction was further subjected to column chromatography (hexane-ethyl acetate, 70:30) to yield compound (I) as colorless crystals (106 mg).

S3. Refinement

All H atoms in compounds (I) were initially located from the difference map·The C bound H atoms were later placed at calculated positions [C—H=0.96–0.98 A°] with U_iso constrained to be 1.5U_eq of the carrrier atom for the methyl group and 1.2U_eq for the remaining positions. The Friedel reflections were merged before final refinement because of the absence of anomalous scattering effects.

Computing details

Data collection: SMART (Siemens, 1996); cell refinement: SAINT (Siemens, 1996); data reduction: SAINT (Siemens, 1996); program(s) used to solve structure: SHELXTL (Sheldrick, 1997); program(s) used to refine structure: SHELXTL (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 1997); software used to prepare material for publication: SHELXTL (Sheldrick, 1997), PARST (Nardelli, 1995) and PLATON (Spek, 2003).

Figures

Fig. 1. The structure of the compound (I) showing 50% probability displacement ellipsoids and the atom numbering scheme.

conessine

Crystal data

C24H40N2	Dx = 1.127 Mg m^−3
Mr = 356.58	Melting point: 398 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
a = 10.4321 (5) Å	Cell parameters from 5789 reflections
b = 10.5977 (5) Å	θ = 2.2–28.3°
c = 19.0145 (9) Å	µ = 0.07 mm^−1
V = 2102.17 (17) Å^3	T = 173 K
Z = 4	Block, colorless
F(000) = 792	0.45 × 0.19 × 0.11 mm

Data collection

Bruker SMART CCD area-detector diffractometer	2955 independent reflections
Radiation source: fine-focus sealed tube	2776 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.034
Detector resolution: 8.33 pixels mm^-1	θmax = 28.3°, θmin = 2.1°
ω scans	h = −13→13
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	k = −13→14
Tmin = 0.972, Tmax = 0.993	l = −25→18
14775 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.048	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.119	H-atom parameters constrained
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0717P)^2 + 0.5901P] where P = (Fo^2 + 2Fc^2)/3
2955 reflections	(Δ/σ)max < 0.001
240 parameters	Δρmax = 0.40 e Å^−3
0 restraints	Δρmin = −0.18 e Å^−3

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
N1	0.33771 (18)	0.85002 (16)	0.75323 (9)	0.0165 (4)
N2	0.30144 (17)	1.59443 (16)	0.37967 (9)	0.0146 (4)
C1	0.4697 (2)	1.12294 (19)	0.64348 (12)	0.0163 (4)
H1A	0.5446	1.1282	0.6134	0.020*
H1B	0.4834	1.1795	0.6829	0.020*
C2	0.4587 (2)	0.98782 (19)	0.67155 (11)	0.0169 (4)
H2A	0.4518	0.9294	0.6324	0.020*
H2B	0.5353	0.9666	0.6980	0.020*
C3	0.3417 (2)	0.97494 (19)	0.71873 (10)	0.0149 (4)
H3A	0.3506	1.0379	0.7561	0.018*
C4	0.22080 (19)	1.01018 (19)	0.67649 (10)	0.0138 (4)
H4A	0.2079	0.9485	0.6395	0.017*
H4B	0.1468	1.0073	0.7073	0.017*
C5	0.23053 (19)	1.14076 (18)	0.64399 (10)	0.0118 (4)
C6	0.13639 (18)	1.22437 (18)	0.65267 (10)	0.0122 (4)
H6A	0.0674	1.2007	0.6807	0.015*
C7	0.13313 (19)	1.35374 (18)	0.62063 (10)	0.0129 (4)
H7A	0.1442	1.4160	0.6575	0.016*
H7B	0.0497	1.3674	0.5995	0.016*
C8	0.23672 (18)	1.37331 (17)	0.56477 (9)	0.0105 (4)
H8A	0.2098	1.3321	0.5210	0.013*
C9	0.36390 (18)	1.31410 (17)	0.58981 (10)	0.0109 (4)
H9A	0.3820	1.3510	0.6360	0.013*
C10	0.35160 (19)	1.16911 (17)	0.60156 (10)	0.0119 (4)
C11	0.47783 (19)	1.35004 (18)	0.54206 (11)	0.0148 (4)
H11A	0.5564	1.3192	0.5632	0.018*
H11B	0.4678	1.3083	0.4970	0.018*
C12	0.49036 (19)	1.49317 (19)	0.52965 (11)	0.0155 (4)
H12A	0.5080	1.5356	0.5738	0.019*
H12B	0.5608	1.5098	0.4977	0.019*
C13	0.36558 (19)	1.54292 (17)	0.49836 (10)	0.0115 (4)
C14	0.25743 (18)	1.51380 (18)	0.55081 (10)	0.0109 (4)
H14A	0.2845	1.5504	0.5958	0.013*
C15	0.14650 (19)	1.59521 (18)	0.52506 (11)	0.0140 (4)
H15A	0.0811	1.6044	0.5609	0.017*
H15B	0.1081	1.5605	0.4828	0.017*
C16	0.2138 (2)	1.72121 (18)	0.51012 (10)	0.0155 (4)
H16A	0.2158	1.7729	0.5522	0.019*
H16B	0.1690	1.7671	0.4735	0.019*
C17	0.3527 (2)	1.68821 (17)	0.48602 (10)	0.0128 (4)
H17A	0.4168	1.7355	0.5129	0.015*
C18	0.37303 (19)	1.70307 (19)	0.40682 (10)	0.0138 (4)
H18A	0.4642	1.6907	0.3965	0.017*
C19	0.3209 (2)	1.5710 (2)	0.30505 (11)	0.0195 (4)
H19A	0.2854	1.6395	0.2783	0.029*
H19B	0.2792	1.4938	0.2920	0.029*
H19C	0.4110	1.5644	0.2955	0.029*
C20	0.3438 (2)	1.48859 (18)	0.42341 (10)	0.0148 (4)
H20A	0.4227	1.4530	0.4051	0.018*
H20B	0.2790	1.4230	0.4244	0.018*
C21	0.3299 (2)	1.82678 (19)	0.37369 (11)	0.0194 (4)
H21A	0.3655	1.8339	0.3273	0.029*
H21B	0.3589	1.8961	0.4020	0.029*
H21C	0.2380	1.8284	0.3708	0.029*
C22	0.3436 (2)	1.09705 (18)	0.53084 (10)	0.0159 (4)
H22A	0.3255	1.0097	0.5397	0.024*
H22B	0.4239	1.1042	0.5064	0.024*
H22C	0.2765	1.1326	0.5025	0.024*
C23	0.2463 (2)	0.8454 (2)	0.81097 (12)	0.0235 (5)
H23A	0.2558	0.7671	0.8359	0.035*
H23B	0.1607	0.8515	0.7927	0.035*
H23C	0.2619	0.9144	0.8425	0.035*
C24	0.3179 (2)	0.7438 (2)	0.70574 (12)	0.0231 (5)
H24A	0.3292	0.6662	0.7310	0.035*
H24B	0.3788	0.7480	0.6680	0.035*
H24C	0.2326	0.7473	0.6869	0.035*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0241 (9)	0.0107 (8)	0.0146 (7)	0.0005 (7)	−0.0013 (7)	0.0028 (6)
N2	0.0175 (8)	0.0135 (8)	0.0128 (7)	−0.0010 (7)	0.0006 (7)	0.0000 (6)
C1	0.0122 (9)	0.0128 (9)	0.0238 (10)	0.0003 (7)	−0.0027 (8)	0.0044 (8)
C2	0.0142 (9)	0.0121 (9)	0.0243 (10)	0.0019 (8)	−0.0020 (8)	0.0046 (8)
C3	0.0191 (10)	0.0097 (8)	0.0159 (8)	−0.0008 (8)	−0.0016 (8)	0.0012 (7)
C4	0.0130 (9)	0.0120 (9)	0.0164 (9)	−0.0017 (7)	0.0002 (7)	0.0008 (7)
C5	0.0125 (8)	0.0117 (8)	0.0111 (8)	−0.0021 (7)	−0.0010 (7)	−0.0006 (7)
C6	0.0114 (8)	0.0143 (9)	0.0110 (8)	−0.0009 (7)	0.0005 (7)	0.0016 (7)
C7	0.0131 (9)	0.0108 (8)	0.0148 (8)	0.0026 (7)	0.0004 (7)	0.0026 (7)
C8	0.0116 (8)	0.0099 (8)	0.0099 (8)	0.0006 (7)	0.0001 (7)	−0.0005 (6)
C9	0.0123 (8)	0.0073 (8)	0.0129 (8)	−0.0007 (7)	−0.0016 (7)	−0.0005 (7)
C10	0.0123 (8)	0.0090 (8)	0.0142 (8)	−0.0001 (7)	−0.0002 (7)	−0.0002 (7)
C11	0.0100 (8)	0.0114 (9)	0.0230 (10)	0.0016 (7)	0.0037 (7)	0.0041 (8)
C12	0.0138 (9)	0.0107 (9)	0.0219 (10)	−0.0020 (7)	−0.0002 (8)	0.0041 (8)
C13	0.0128 (9)	0.0074 (8)	0.0142 (8)	−0.0006 (7)	0.0008 (7)	0.0013 (7)
C14	0.0126 (8)	0.0086 (8)	0.0114 (8)	0.0011 (7)	−0.0007 (7)	−0.0014 (7)
C15	0.0137 (9)	0.0118 (8)	0.0164 (8)	0.0035 (8)	0.0017 (8)	0.0004 (7)
C16	0.0195 (10)	0.0106 (9)	0.0166 (9)	0.0033 (8)	0.0003 (8)	0.0009 (7)
C17	0.0152 (9)	0.0070 (8)	0.0161 (9)	0.0005 (7)	−0.0031 (7)	0.0007 (7)
C18	0.0134 (9)	0.0117 (9)	0.0162 (9)	0.0001 (7)	−0.0014 (7)	0.0028 (7)
C19	0.0200 (10)	0.0234 (11)	0.0151 (9)	−0.0023 (8)	−0.0002 (8)	0.0000 (8)
C20	0.0171 (9)	0.0105 (8)	0.0168 (9)	−0.0005 (8)	0.0040 (8)	−0.0010 (7)
C21	0.0223 (10)	0.0156 (10)	0.0203 (10)	0.0001 (8)	−0.0054 (8)	0.0051 (8)
C22	0.0206 (10)	0.0117 (8)	0.0154 (9)	0.0007 (8)	0.0046 (8)	−0.0009 (7)
C23	0.0305 (12)	0.0182 (10)	0.0218 (10)	0.0016 (9)	0.0044 (9)	0.0080 (8)
C24	0.0345 (12)	0.0121 (9)	0.0227 (10)	−0.0017 (9)	−0.0021 (9)	0.0030 (8)

Geometric parameters (Å, º)

N1—C23	1.455 (3)	C12—C13	1.525 (3)
N1—C24	1.458 (3)	C12—H12A	0.9700
N1—C3	1.478 (2)	C12—H12B	0.9700
N2—C19	1.455 (3)	C13—C14	1.537 (3)
N2—C20	1.465 (3)	C13—C20	1.554 (3)
N2—C18	1.466 (3)	C13—C17	1.563 (3)
C1—C2	1.533 (3)	C14—C15	1.524 (3)
C1—C10	1.547 (3)	C14—H14A	0.9800
C1—H1A	0.9700	C15—C16	1.535 (3)
C1—H1B	0.9700	C15—H15A	0.9700
C2—C3	1.521 (3)	C15—H15B	0.9700
C2—H2A	0.9700	C16—C17	1.559 (3)
C2—H2B	0.9700	C16—H16A	0.9700
C3—C4	1.541 (3)	C16—H16B	0.9700
C3—H3A	0.9800	C17—C18	1.529 (3)
C4—C5	1.519 (3)	C17—H17A	0.9800
C4—H4A	0.9700	C18—C21	1.523 (3)
C4—H4B	0.9700	C18—H18A	0.9800
C5—C6	1.333 (3)	C19—H19A	0.9600
C5—C10	1.529 (3)	C19—H19B	0.9600
C6—C7	1.501 (3)	C19—H19C	0.9600
C6—H6A	0.9300	C20—H20A	0.9700
C7—C8	1.529 (3)	C20—H20B	0.9700
C7—H7A	0.9700	C21—H21A	0.9600
C7—H7B	0.9700	C21—H21B	0.9600
C8—C14	1.528 (3)	C21—H21C	0.9600
C8—C9	1.543 (3)	C22—H22A	0.9600
C8—H8A	0.9800	C22—H22B	0.9600
C9—C11	1.543 (3)	C22—H22C	0.9600
C9—C10	1.558 (3)	C23—H23A	0.9600
C9—H9A	0.9800	C23—H23B	0.9600
C10—C22	1.549 (3)	C23—H23C	0.9600
C11—C12	1.541 (3)	C24—H24A	0.9600
C11—H11A	0.9700	C24—H24B	0.9600
C11—H11B	0.9700	C24—H24C	0.9600
C23—N1—C24	110.38 (18)	C12—C13—C14	107.69 (15)
C23—N1—C3	112.55 (17)	C12—C13—C20	110.76 (16)
C24—N1—C3	114.87 (16)	C14—C13—C20	114.42 (16)
C19—N2—C20	112.41 (16)	C12—C13—C17	118.20 (16)
C19—N2—C18	113.96 (17)	C14—C13—C17	103.40 (15)
C20—N2—C18	104.34 (15)	C20—C13—C17	102.40 (15)
C2—C1—C10	114.53 (17)	C15—C14—C8	120.00 (16)
C2—C1—H1A	108.6	C15—C14—C13	103.61 (15)
C10—C1—H1A	108.6	C8—C14—C13	114.35 (15)
C2—C1—H1B	108.6	C15—C14—H14A	106.0
C10—C1—H1B	108.6	C8—C14—H14A	106.0
H1A—C1—H1B	107.6	C13—C14—H14A	106.0
C3—C2—C1	110.45 (17)	C14—C15—C16	101.81 (16)
C3—C2—H2A	109.6	C14—C15—H15A	111.4
C1—C2—H2A	109.6	C16—C15—H15A	111.4
C3—C2—H2B	109.6	C14—C15—H15B	111.4
C1—C2—H2B	109.6	C16—C15—H15B	111.4
H2A—C2—H2B	108.1	H15A—C15—H15B	109.3
N1—C3—C2	111.37 (17)	C15—C16—C17	106.51 (15)
N1—C3—C4	115.19 (17)	C15—C16—H16A	110.4
C2—C3—C4	109.12 (16)	C17—C16—H16A	110.4
N1—C3—H3A	106.9	C15—C16—H16B	110.4
C2—C3—H3A	106.9	C17—C16—H16B	110.4
C4—C3—H3A	106.9	H16A—C16—H16B	108.6
C5—C4—C3	112.22 (16)	C18—C17—C16	113.29 (16)
C5—C4—H4A	109.2	C18—C17—C13	103.72 (15)
C3—C4—H4A	109.2	C16—C17—C13	104.89 (16)
C5—C4—H4B	109.2	C18—C17—H17A	111.5
C3—C4—H4B	109.2	C16—C17—H17A	111.5
H4A—C4—H4B	107.9	C13—C17—H17A	111.5
C6—C5—C4	120.40 (18)	N2—C18—C21	112.33 (16)
C6—C5—C10	122.92 (18)	N2—C18—C17	101.25 (15)
C4—C5—C10	116.68 (16)	C21—C18—C17	117.07 (17)
C5—C6—C7	125.01 (18)	N2—C18—H18A	108.6
C5—C6—H6A	117.5	C21—C18—H18A	108.6
C7—C6—H6A	117.5	C17—C18—H18A	108.6
C6—C7—C8	112.94 (16)	N2—C19—H19A	109.5
C6—C7—H7A	109.0	N2—C19—H19B	109.5
C8—C7—H7A	109.0	H19A—C19—H19B	109.5
C6—C7—H7B	109.0	N2—C19—H19C	109.5
C8—C7—H7B	109.0	H19A—C19—H19C	109.5
H7A—C7—H7B	107.8	H19B—C19—H19C	109.5
C14—C8—C7	110.66 (15)	N2—C20—C13	106.33 (15)
C14—C8—C9	109.17 (15)	N2—C20—H20A	110.5
C7—C8—C9	109.76 (15)	C13—C20—H20A	110.5
C14—C8—H8A	109.1	N2—C20—H20B	110.5
C7—C8—H8A	109.1	C13—C20—H20B	110.5
C9—C8—H8A	109.1	H20A—C20—H20B	108.7
C8—C9—C11	112.35 (15)	C18—C21—H21A	109.5
C8—C9—C10	111.99 (16)	C18—C21—H21B	109.5
C11—C9—C10	113.03 (16)	H21A—C21—H21B	109.5
C8—C9—H9A	106.3	C18—C21—H21C	109.5
C11—C9—H9A	106.3	H21A—C21—H21C	109.5
C10—C9—H9A	106.3	H21B—C21—H21C	109.5
C5—C10—C1	108.91 (15)	C10—C22—H22A	109.5
C5—C10—C22	108.48 (15)	C10—C22—H22B	109.5
C1—C10—C22	109.53 (16)	H22A—C22—H22B	109.5
C5—C10—C9	109.73 (16)	C10—C22—H22C	109.5
C1—C10—C9	108.67 (16)	H22A—C22—H22C	109.5
C22—C10—C9	111.49 (15)	H22B—C22—H22C	109.5
C12—C11—C9	113.48 (16)	N1—C23—H23A	109.5
C12—C11—H11A	108.9	N1—C23—H23B	109.5
C9—C11—H11A	108.9	H23A—C23—H23B	109.5
C12—C11—H11B	108.9	N1—C23—H23C	109.5
C9—C11—H11B	108.9	H23A—C23—H23C	109.5
H11A—C11—H11B	107.7	H23B—C23—H23C	109.5
C13—C12—C11	109.12 (16)	N1—C24—H24A	109.5
C13—C12—H12A	109.9	N1—C24—H24B	109.5
C11—C12—H12A	109.9	H24A—C24—H24B	109.5
C13—C12—H12B	109.9	N1—C24—H24C	109.5
C11—C12—H12B	109.9	H24A—C24—H24C	109.5
H12A—C12—H12B	108.3	H24B—C24—H24C	109.5
C10—C1—C2—C3	−58.0 (2)	C11—C12—C13—C14	59.3 (2)
C23—N1—C3—C2	165.95 (18)	C11—C12—C13—C20	−66.5 (2)
C24—N1—C3—C2	−66.6 (2)	C11—C12—C13—C17	175.91 (17)
C23—N1—C3—C4	−69.1 (2)	C7—C8—C14—C15	−59.3 (2)
C24—N1—C3—C4	58.3 (2)	C9—C8—C14—C15	179.75 (16)
C1—C2—C3—N1	−173.11 (16)	C7—C8—C14—C13	176.63 (15)
C1—C2—C3—C4	58.6 (2)	C9—C8—C14—C13	55.7 (2)
N1—C3—C4—C5	178.69 (15)	C12—C13—C14—C15	165.73 (15)
C2—C3—C4—C5	−55.2 (2)	C20—C13—C14—C15	−70.66 (19)
C3—C4—C5—C6	−129.52 (19)	C17—C13—C14—C15	39.87 (18)
C3—C4—C5—C10	50.8 (2)	C12—C13—C14—C8	−61.9 (2)
C4—C5—C6—C7	−177.33 (17)	C20—C13—C14—C8	61.7 (2)
C10—C5—C6—C7	2.4 (3)	C17—C13—C14—C8	172.26 (15)
C5—C6—C7—C8	11.1 (3)	C8—C14—C15—C16	−173.52 (16)
C6—C7—C8—C14	−162.15 (16)	C13—C14—C15—C16	−44.50 (18)
C6—C7—C8—C9	−41.6 (2)	C14—C15—C16—C17	31.96 (19)
C14—C8—C9—C11	−48.7 (2)	C15—C16—C17—C18	104.67 (18)
C7—C8—C9—C11	−170.16 (15)	C15—C16—C17—C13	−7.77 (19)
C14—C8—C9—C10	−177.18 (15)	C12—C13—C17—C18	102.76 (19)
C7—C8—C9—C10	61.4 (2)	C14—C13—C17—C18	−138.40 (16)
C6—C5—C10—C1	134.57 (19)	C20—C13—C17—C18	−19.2 (2)
C4—C5—C10—C1	−45.7 (2)	C12—C13—C17—C16	−138.15 (18)
C6—C5—C10—C22	−106.3 (2)	C14—C13—C17—C16	−19.32 (18)
C4—C5—C10—C22	73.4 (2)	C20—C13—C17—C16	99.87 (17)
C6—C5—C10—C9	15.7 (2)	C19—N2—C18—C21	64.1 (2)
C4—C5—C10—C9	−164.58 (16)	C20—N2—C18—C21	−172.98 (17)
C2—C1—C10—C5	49.1 (2)	C19—N2—C18—C17	−170.26 (17)
C2—C1—C10—C22	−69.4 (2)	C20—N2—C18—C17	−47.29 (18)
C2—C1—C10—C9	168.55 (17)	C16—C17—C18—N2	−72.50 (19)
C8—C9—C10—C5	−47.1 (2)	C13—C17—C18—N2	40.64 (19)
C11—C9—C10—C5	−175.22 (15)	C16—C17—C18—C21	50.0 (2)
C8—C9—C10—C1	−166.09 (15)	C13—C17—C18—C21	163.11 (17)
C11—C9—C10—C1	65.8 (2)	C19—N2—C20—C13	159.37 (17)
C8—C9—C10—C22	73.1 (2)	C18—N2—C20—C13	35.4 (2)
C11—C9—C10—C22	−55.0 (2)	C12—C13—C20—N2	−135.88 (16)
C8—C9—C11—C12	51.7 (2)	C14—C13—C20—N2	102.18 (18)
C10—C9—C11—C12	179.59 (17)	C17—C13—C20—N2	−9.0 (2)
C9—C11—C12—C13	−56.9 (2)