(Z)-3α-(1,3-Dioxoisoindolin-2-yl)-17(20)-pregnene.

Abstract

The title compound, C(29)H(37)NO(2), crystallized with two independent mol-ecules in an asymmetric unit in which the conformation of the cyclo-hexyl ring of the pregnene moiety bonded to the 3α-(1,3-dioxoisoindolin-2-yl)- ring system differs: in one mol-ecule it is in a chair conformation, while in the other it exhibits a half-chair conformation. The other six-membered rings in the pregnene moiety are in chair conformations and the five-membered rings are in envelope forms in both mol-ecules. In both mol-ecules, the 3α-(1,3-dioxoisoindolin-2-yl)- ring systems are individually approximately planar, with r.m.s. devtaions 0.0148 and 0.0264 Å. The structure is consolidated by inter-molecular C-H⋯O hydrogen-bonding inter-actions involving the carbonyl O atoms and methyl, methyl-ene and methyl-idyne groups, resulting in a two-dimensional structure.

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(Z)-3a-(1,3-Dioxoisoindolin-2-yl)-17(20)-
pregnene
Yue Qi, Nan Qin and Hong-Quan Duan*
School of Pharmaceutical Sciences, Research Center of Basic Medical Scienses,
Tianjin Medical University, Tianjin 300070, People’s Republic of China
Correspondence e-mail: duanhq@tijmu.edu.cn
Received 21 June 2011; accepted 11 July 2011
Key indicators: single-crystal X-ray study; T = 113 K; mean ?(C–C) = 0.003 A ˚;
R factor = 0.039; wR factor = 0.096; data-to-parameter ratio = 9.7.
The title compound, C29H37NO2, crystallized with two
independent molecules in an asymmetric unit in which the
conformation of the cyclohexyl ring of the pregnene moiety
bonded to the 3?-(1,3-dioxoisoindolin-2-yl)- ring system
differs: in one molecule it is in a chair conformation, while
in the other it exhibits a half-chair conformation. The other
six-membered rings in the pregnene moiety are in chair
conformations and the five-membered rings are in envelope
forms in both molecules. In both molecules, the 3?-(1,3-
dioxoisoindolin-2-yl)- ring systems are individually approxi-
mately planar, with r.m.s. devtaions 0.0148 and 0.0264 A˚. The
structure isconsolidated by
hydrogen-bonding interactions involving the carbonyl O
atoms and methyl, methylene and methylidyne groups,
resulting in a two-dimensional structure.
intermolecularC—H???O
Related literature
The title compound was synthesized from epiandrosterone, a
pregnane alkaloid isolated from Pachysandra axillaris, a
traditional chinese medicine. For the biological activity of
Pachysandra axillaris, see: Sun et al. (2010). For the synthesis
of the title compound, see: Batcho et al. (1981). For a related
structure, see: Ishida et al. (1981). For the absolute structure,
see: Pollard & Ahmed (1971).
Experimental
Crystal data
C29H37NO2
Mr= 431.60
Monoclinic, P21
a = 7.5895 (10) A˚
b = 31.355 (3) A˚
c = 9.8912 (12) A˚
? = 93.056 (6)?
V = 2350.4 (5) A˚3
Z = 4
Mo K? radiation
? = 0.08 mm?1
T = 113 K
0.22 ? 0.20 ? 0.12 mm
Data collection
Rigaku Saturn724 CCD
diffractometer
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC,
2005)
Tmin= 0.984, Tmax= 0.991
17383 measured reflections
5642 independent reflections
5296 reflections with I > 2?(I)
Rint= 0.052
Refinement
R[F2> 2?(F2)] = 0.039
wR(F2) = 0.096
S = 1.04
5642 reflections
583 parameters
1 restraint
H-atom parameters constrained
??max= 0.26 e A˚?3
??min= ?0.27 e A˚?3
Table 1
Hydrogen-bond geometry (A˚,?).
D—H???A
C1—H1B???O2
C5—H5???O4i
C21—H21C???O3ii
C31—H31A???O2iii
Symmetry codes: (i) x;y;z þ 1; (ii) x ? 1;y;z; (iii) x þ 1;y;z ? 1.
D—HH???AD???AD—H???A
0.99
1.00
0.98
0.99
2.25
2.59
2.60
2.47
3.027 (3)
3.237 (3)
3.501 (3)
3.361 (3)
134
122
153
150
Data collection: CrystalClear (Rigaku/MSC, 2005); cell refinement:
CrystalClear; data reduction: CrystalClear; program(s) used to solve
structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine
structure: SHELXL97 (Sheldrick,
SHELXTL (Sheldrick, 2008); software used to prepare material for
publication: CrystalStructure (Rigaku/MSC, 2005).
2008);molecular graphics:
This work was supported by the National Natural Science
Foundation of China (No. 81072540). The authors are grateful
to the Central Laboratory of Nankai University for the data
collection. Special thanks go to Dr Xie Chengzhi (School of
Pharmaceutical Sciences, Tianjin Medical University) for his
invaluable support.
Supplementary data and figures for this paper are available from the
IUCr electronic archives (Reference: PV2421).
References
Batcho, A. D., Berger, D. E., Davoust, S. G., Wovkulich, P. M. & Uskokovic, M.
R. (1981). Helv. Chim. Acta, 64, 16–82.
Ishida, T., Inoue, M., Harusawa, S., Hamada, Y. & Shioiri, T. (1981). Acta
Cryst. B37, 1881–1884.
Pollard, D. R. & Ahmed, F. R. (1971). Acta Cryst. B27, 1976–1982.
Rigaku/MSC. (2005). CrystalClear and CrystalStructure. Rigaku/MSC, The
Woodlands, Texas, USA.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
Sun, Y., Yan, Y. X., Chen, J. C., Lu, L., Zhang, X. M., Li, Y. & Qiu, M. H.
(2010). Steroids, 75, 818–824.
organic compounds
Acta Cryst. (2011). E67, o2065 doi:10.1107/S1600536811027632 Qi et al.
o2065
Acta Crystallographica Section E
Structure Reports
Online
ISSN 1600-5368

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supplementary materials

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supplementary materials
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Acta Cryst. (2011). E67, o2065 [ doi:10.1107/S1600536811027632 ]
(Z)-3 -(1,3-Dioxoisoindolin-2-yl)-17(20)-pregnene
Y. Qi, N. Qin and H.-Q. Duan
Comment
The title compound was synthesized from epiandrosterone which is a pregnane alkaloids isolated from Pachysandra axil-
laris, a Traditional Chinese Medicine (TCM). The pregnane alkaloids from Pachysandra axillaris had been reported to be
effective as anticancer (Sun et al., 2010).
The title compound, crystallizes with two independent molecules in an asymmetric unit. The cyclohexyl rings (A) of the
pregnene moiety bonded to the 3α-(1,3-dioxoisoindolin-2-yl)- ring system in both molecules differ in conformations; in one
molecule (Fig. 1) it is in a chair conformation while in the other molecule (Fig. 2) it exhibits a half chair conformation. The
conformations of the rings B–D in the two molecules are identical with six membered rings (B & C) in chair conformations
and the five membered rings in envelope forms in both molecules. In both molecules, the 3α-(1,3-dioxoisoindolin-2-yl)- ring
systems are individually planar with rms devtaions 0.0148 and 0.0264 Å. The structure is consolidated by intermolecular
hydrogen bonding interactions of the type C—H···O involving carbonyl O atoms and methyl, methylene and methylidyne
groups, resulting in a two-dimensional structure (Fig. 3).
Experimental
The title compound was prepared by following a literature procedure (Batcho et al., 1981). A solution of potassium t-but-
oxide (t-BuOK) (2.28 g, 20.0 mmol) in 15 ml THF was added to a suspension of Ph3PEtBr (7.58 g, 20.0 mmol), in 25 ml
dry THF, and was stirred for 1 h at room temperature. The mixture was refluxed for another 4 h after adding epiandroster-
one (1.45 g, 5.0 mmol). The residue thus obtained was purified by recrystallization from MeOH to afford 1 (675.8 mg,
45%; Fig. 4). To a solution of 1 (86.9 mg, 0.287 mmol) and triphenylphosphine (85.1 mg, 0.324 mmol) in THF (12 ml),
phthalimide (46.5 mg, 0.316 mmol) and diisopropyl azodicarboxylate (63.9 mg, 0.316 mmol) were added, and the mixture
was stirred for 18 h at room temperature. The residue was purified by crystallization from MeOH to afford the title com-
pound, 2 (78.0 mg, 63%) as a white solid. The crystals of 2 were obtained by slow evaporation of its solution using a mixed
solvent MeOH/CH2Cl2 (1:1).
Refinement
H atoms were placed at calculated positions with C—H = 0.95 Å (aryl), 0.98 (methylene), 0.99 (methyl) and 1.00 Å
(methyne) and were refined in the riding-model approximation with Uiso = 1.2–1.5 times Ueq of the parent atoms. As the
structure has no anomalous scatterer, an absolute structure could not be established in this analysis; the Friedel-pairs (3600)
of reflections were merged.

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Figures
Fig. 1. One independent molecule in the asymmetric unit of the title compound, with 30%
probability displacement ellipsoids.
Fig. 2. The other independent molecule in the asymmetric unit of the title compound, with
30% probability displacement ellipsoids.
Fig. 3. The packing of the title compound, showing the two-dimensional structure, with inter-
molecular hydrogen bonds (dashed lines); for clarity H atoms not involved in H-bonds have
been omitted.
Fig. 4. The scheme of synthesis of the title compound.
(Z)-3α-(1,3-Dioxoisoindolin-2-yl)-17 (20)-pregnene
Crystal data
C29H37NO2
F(000) = 936
Dx = 1.220 Mg m−3
Mo Kα radiation, λ = 0.71073 Å
Cell parameters from 7024 reflections
θ = 1.9–28.4°
µ = 0.08 mm−1
T = 113 K
Prism, colorless
Mr = 431.60
Monoclinic, P21
Hall symbol: P 2yb
a = 7.5895 (10) Å
b = 31.355 (3) Å
c = 9.8912 (12) Å
β = 93.056 (6)°
V = 2350.4 (5) Å3
Z = 4
0.22 × 0.20 × 0.12 mm
Data collection
Rigaku Saturn724 CCD
diffractometer
Radiation source: rotating anode
multilayer
Detector resolution: 14.22 pixels mm-1
ω and φ scans
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)
5642 independent reflections
5296 reflections with I > 2σ(I)
Rint = 0.052
θmax = 27.9°, θmin = 2.1°
h = −9→9
k = −41→35

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supplementary materials
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Tmin = 0.984, Tmax = 0.991
17383 measured reflections
l = −12→13
Refinement
Refinement on F2
Primary atom site location: structure-invariant direct
methods
Secondary atom site location: difference Fourier map
Hydrogen site location: inferred from neighbouring
sites
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.039
wR(F2) = 0.096
H-atom parameters constrained
S = 1.04
w = 1/[σ2(Fo2) + (0.0522P)2 + 0.1053P]
where P = (Fo2 + 2Fc2)/3
(Δ/σ)max < 0.001
Δρmax = 0.26 e Å−3
Δρmin = −0.27 e Å−3
5642 reflections
583 parameters
1 restraint
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 mat-
rix. 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, convention-
al 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)
x
0.0919 (2)
−0.0642 (2)
0.6594 (2)
0.4062 (2)
−0.0051 (2)
0.5259 (2)
−0.2120 (3)
−0.3231
−0.1964
−0.2298 (3)
−0.3138
−0.2824
−0.0590 (3)
−0.0820
0.0929 (3)
0.0725
y
0.42410 (5)
0.30027 (5)
0.33129 (5)
0.30622 (5)
0.35800 (5)
0.30729 (5)
0.27009 (6)
0.2561
0.2647
0.31824 (7)
0.3296
0.3229
0.34439 (6)
0.3712
0.32200 (6)
0.3237
z
0.94269 (15)
1.15244 (15)
0.49697 (15)
0.07334 (14)
1.01138 (16)
0.29473 (16)
0.8787 (2)
0.8459
0.9772
0.8555 (2)
0.9197
0.7629
0.87136 (19)
0.8188
0.80395 (19)
0.7044
Uiso*/Ueq
0.0332 (4)
0.0323 (4)
0.0363 (4)
0.0282 (3)
0.0212 (3)
0.0209 (3)
0.0226 (4)
0.027*
0.027*
0.0245 (4)
0.029*
0.029*
0.0224 (4)
0.027*
0.0222 (4)
0.027*
O1
O2
O3
O4
N1
N2
C1
H1A
H1B
C2
H2A
H2B
C3
H3
C4
H4A