(±)-(4bS,8aR,10aS)-10a-Ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octa­hydro­phenanthrene-2,6-dicarbonitrile

Zheng, S.; Resch, D.; Honda, T.; Jasinski, J.P.

doi:10.1107/S1600536812041244

Volume 68
Part 11
Pages o3095-o3096
November 2012

Received 17 August 2012
Accepted 1 October 2012
Online 10 October 2012

Key indicators
Single-crystal X-ray study
T = 299 K
Mean (C-C) = 0.003 Å
R = 0.050
wR = 0.140
Data-to-parameter ratio = 14.1
Details

(±)-(4bS,8aR,10aS)-10a-Ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile

Suqing Zheng,^a Daniel Resch,^b Tadashi Honda ^a,^b and Jerry P. Jasinski ^c ^*

^aInstitute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, NY 11794, USA,^bDepartment of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA, and ^cDepartment of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA
Correspondence e-mail: jjasinski@keene.edu

The anti-inflammatory and cytoprotective tricyclic title compound, C₂₁H₁₈N₂O₂, also known as TBE-31, crystallizes with two nearly superimposable molecules in the asymmetric unit. In both molecules, the three ring systems conform to an envelope-chair-planar arrangement. The central ring, in a cyclohexane chair conformation, contains an axial ethynyl group that bends slightly off from a nearby axial methyl group because of the 1,3-diaxial repulsion between the two groups. In the crystal, weak C-HN and C-HO interactions form chains along [001].

Related literature

For anti-inflammatory, growth suppressive, and proapoptotic properties of TBE-31 and the structural assignment of racemic TBE-31 by NMR spectroscopy, see: Honda et al. (2007, 2011). For inducing NQO1 and GST in the liver, skin, and stomach in mice, see: Dinkova-Kostova et al. (2010). For TBE-31 activity against aflatoxin-induced liver cancer in rats, see: Liby et al. (2008). For reactivity of the non-enolizable cyanoenone in ring C of TBE-31 compared to that of MCE-1, see: Dinkova-Kostova et al. (2010). For the biological potency in bioassays for inhibition of inflammation and carcinogenesis and related biological potency, see: Zheng et al. (2012). For the synthesis of TBE-31, see: Honda et al. (2011). For literature on the number of chemical formula units per asymmetric unit, Z', see: Steiner (2000); Steed (2003); Gavezzotti (2008). For ring-puckering parameters, see: Cremer & Pople (1975). For all-trans-perhydrophenanthrene comparisons, see: Marcos et al. (2005). For a related structure, see: Bore et al. (2002).

Experimental

Crystal data

C₂₁H₁₈N₂O₂
M_r = 330.37
Triclinic, $[P \overline 1]$
a = 7.3012 (2) Å
b = 12.9843 (3) Å
c = 18.4254 (4) Å
= 95.051 (2)°
= 96.284 (2)°
= 92.338 (2)°
V = 1727.26 (7) Å³
Z = 4
Cu K radiation
= 0.66 mm^-1
T = 299 K
0.71 × 0.46 × 0.29 mm

Data collection

Oxford Diffraction Xcalibur Atlas Gemini diffractometer
Absorption correction: Gaussian (CrysAlis RED; Oxford Diffraction, 2010 $[Oxford Diffraction (2010). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.]$ ) T_min = 0.745, T_max = 0.897
33944 measured reflections
6478 independent reflections
5160 reflections with I > 2(I)
R_int = 0.035

Refinement

R[F² > 2(F²)] = 0.050
wR(F²) = 0.140
S = 1.03
6478 reflections
458 parameters
H-atom parameters constrained
_max = 0.22 e Å^-3
_min = -0.18 e Å^-3

Table 1
Hydrogen-bond geometry (Å, °)

D-HA	D-H	HA	DA	D-HA
C4A-H4AN2Bⁱ	0.93	2.66	3.572 (3)	166
C4B-H4BN2Aⁱ	0.93	2.69	3.580 (2)	161
C7B-H7BO1Bⁱⁱ	0.93	2.43	3.246 (2)	146
C13B-H13DO1Bⁱⁱⁱ	0.97	2.38	3.324 (2)	163
C13B-H13CO2A^iv	0.97	2.57	3.435 (2)	148
C13A-H13AO1Aⁱ	0.97	2.37	3.295 (2)	159
Symmetry codes: (i) -x+1, -y+1, -z+1; (ii) -x, -y+1, -z; (iii) -x+1, -y+1, -z; (iv) x, y, z-1.

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 $[Oxford Diffraction (2010). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.]$ ); cell refinement: CrysAlis RED (Oxford Diffraction, 2010 $[Oxford Diffraction (2010). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.]$ ); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: WinGX (Farrugia, 1999); software used to prepare material for publication: Mercury (Macrae et al., 2006), PLATON (Spek, 2009) and publCIF (Westrip, 2010).

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: QK2041 ).

Acknowledgements

We thank Drs Iwao Ojima and Nancy S. Goroff for their helpful suggestions and discussions. This investigation was supported by funds from NIH grant R03-CA105294 and Reata Pharmaceuticals. The Stony Brook University single-crystal diffractometer was obtained through the support of the National Science Foundation (NSF) grant CHE-0840483.

References

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