Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807051215/cs2048sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807051215/cs2048Isup2.hkl |
CCDC reference: 655271
Key indicators
- Single-crystal X-ray study
- T = 173 K
- Mean (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
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).
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 Uiso constrained to be 1.5Ueq of the carrrier atom for the methyl group and 1.2Ueq for the remaining positions. The Friedel reflections were merged before final refinement because of the absence of anomalous scattering effects.
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.
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).
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).
Fig. 1. The structure of the compound (I) showing 50% probability displacement ellipsoids and the atom numbering scheme. |
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) Å3 | T = 173 K |
Z = 4 | Block, colorless |
F(000) = 792 | 0.45 × 0.19 × 0.11 mm |
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 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)] = 0.048 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.119 | H-atom parameters constrained |
S = 1.06 | w = 1/[σ2(Fo2) + (0.0717P)2 + 0.5901P] where P = (Fo2 + 2Fc2)/3 |
2955 reflections | (Δ/σ)max < 0.001 |
240 parameters | Δρmax = 0.40 e Å−3 |
0 restraints | Δρmin = −0.18 e Å−3 |
C24H40N2 | V = 2102.17 (17) Å3 |
Mr = 356.58 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 10.4321 (5) Å | µ = 0.07 mm−1 |
b = 10.5977 (5) Å | T = 173 K |
c = 19.0145 (9) Å | 0.45 × 0.19 × 0.11 mm |
Bruker SMART CCD area-detector diffractometer | 2955 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 2776 reflections with I > 2σ(I) |
Tmin = 0.972, Tmax = 0.993 | Rint = 0.034 |
14775 measured reflections |
R[F2 > 2σ(F2)] = 0.048 | 0 restraints |
wR(F2) = 0.119 | H-atom parameters constrained |
S = 1.06 | Δρmax = 0.40 e Å−3 |
2955 reflections | Δρmin = −0.18 e Å−3 |
240 parameters |
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. |
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* |
U11 | U22 | U33 | U12 | U13 | U23 | |
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) |
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) |
Experimental details
Crystal data | |
Chemical formula | C24H40N2 |
Mr | 356.58 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 173 |
a, b, c (Å) | 10.4321 (5), 10.5977 (5), 19.0145 (9) |
V (Å3) | 2102.17 (17) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.07 |
Crystal size (mm) | 0.45 × 0.19 × 0.11 |
Data collection | |
Diffractometer | Bruker SMART CCD area-detector |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1996) |
Tmin, Tmax | 0.972, 0.993 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 14775, 2955, 2776 |
Rint | 0.034 |
(sin θ/λ)max (Å−1) | 0.667 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.048, 0.119, 1.06 |
No. of reflections | 2955 |
No. of parameters | 240 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.40, −0.18 |
Computer programs: SMART (Siemens, 1996), SAINT (Siemens, 1996), SHELXTL (Sheldrick, 1997), PARST (Nardelli, 1995) and PLATON (Spek, 2003).
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.