[Journal logo]

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 [sigma](C-C) = 0.003 Å
R = 0.050
wR = 0.140
Data-to-parameter ratio = 14.1
Details
Open access

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

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-H...N and C-H...O 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[Honda, T., Sundararajan, C., Yoshizawa, H., Su, X., Honda, Y., Liby, K. T., Sporn, M. B. & Gribble, G. W. (2007). J. Med. Chem. 50, 1731-1734.], 2011[Honda, T., Yoshizawa, H., Sundararajan, C., David, E., Lajoie, M. J., Favaloro, F. G. Jr, Janosik, T., Su, X., Honda, Y., Roebuck, B. D. & Gribble, G. W. (2011). J. Med. Chem. 54, 1762-1778.]). For inducing NQO1 and GST in the liver, skin, and stomach in mice, see: Dinkova-Kostova et al. (2010[Dinkova-Kostova, A. T., Talalay, P., Sharkey, J., Zhang, Y., Holtzclaw, W. D., Xiu Jun Wang, X. J., David, E., Schiavoni, K. H., Finlayson, S., Dale, F., Mierke, D. F. & Honda, T. (2010). J. Biol. Chem. 285, 33747-33755.]). For TBE-31 activity against aflatoxin-induced liver cancer in rats, see: Liby et al. (2008[Liby, K., Yore, M. M., Roebuck, B. D., Baumgartner, K. J., Honda, T., Sundararajan, C., Yoshizawa, H., Gribble, G. W., Williams, C. R., Risingsong, R., Royce, D. B., Dinkova-Kostova, A. T., Stephenson, K. K., Egner, P. A., Yates, M. S., Groopman, J. D., Kensler, T. W. & Sporn, M. B. (2008). Cancer Res. 68, 6727-6732.]). 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[Dinkova-Kostova, A. T., Talalay, P., Sharkey, J., Zhang, Y., Holtzclaw, W. D., Xiu Jun Wang, X. J., David, E., Schiavoni, K. H., Finlayson, S., Dale, F., Mierke, D. F. & Honda, T. (2010). J. Biol. Chem. 285, 33747-33755.]). For the biological potency in bioassays for inhibition of inflammation and carcinogenesis and related biological potency, see: Zheng et al. (2012[Zheng, S., Laximi, Y. R. S., David, E., Dinkova-Kostova, A. T., Shiavoni, K. H., Ren, Y., Zheng, Y., Trevino, I., Bumeister, R., Ojima, I., Wigley, W. C., Bliska, J. B., Mierke, D. F. & Honda, T. (2012). J. Med. Chem. 55, 4837-4846.]). For the synthesis of TBE-31, see: Honda et al. (2011[Honda, T., Yoshizawa, H., Sundararajan, C., David, E., Lajoie, M. J., Favaloro, F. G. Jr, Janosik, T., Su, X., Honda, Y., Roebuck, B. D. & Gribble, G. W. (2011). J. Med. Chem. 54, 1762-1778.]). For literature on the number of chemical formula units per asymmetric unit, Z', see: Steiner (2000[Steiner, T. (2000). Acta Cryst. B56, 673-676.]); Steed (2003[Steed, J. W. (2003). CrystEngComm, 5, 169-179.]); Gavezzotti (2008[Gavezzotti, A. (2008). CrystEngComm, 10, 389-398.]). For ring-puckering parameters, see: Cremer & Pople (1975[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.]). For all-trans-perhydrophenanthrene comparisons, see: Marcos et al. (2005[Marcos, I. S., Cubillo, M. A., Moro, R. F., Carballares, S., Díez, D., Basabe, P., Llamazares, C. F., Benéitez, A., Sanz, F., Broughton, H. B. & Urones, J. G. (2005). Tetrahedron, 61, 977-1003.]). For a related structure, see: Bore et al. (2002[Bore, L., Honda, T., Gribble, G. W., Lork, E. & Jasinski, J. P. (2002). Acta Cryst. C58, o199-o200.]).

[Scheme 1]

Experimental

Crystal data
  • C21H18N2O2

  • Mr = 330.37

  • Triclinic, [P \overline 1]

  • a = 7.3012 (2) Å

  • b = 12.9843 (3) Å

  • c = 18.4254 (4) Å

  • [alpha] = 95.051 (2)°

  • [beta] = 96.284 (2)°

  • [gamma] = 92.338 (2)°

  • V = 1727.26 (7) Å3

  • Z = 4

  • Cu K[alpha] radiation

  • [mu] = 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.]) Tmin = 0.745, Tmax = 0.897

  • 33944 measured reflections

  • 6478 independent reflections

  • 5160 reflections with I > 2[sigma](I)

  • Rint = 0.035

Refinement
  • R[F2 > 2[sigma](F2)] = 0.050

  • wR(F2) = 0.140

  • S = 1.03

  • 6478 reflections

  • 458 parameters

  • H-atom parameters constrained

  • [Delta][rho]max = 0.22 e Å-3

  • [Delta][rho]min = -0.18 e Å-3

Table 1
Hydrogen-bond geometry (Å, °)

D-H...A D-H H...A D...A D-H...A
C4A-H4A...N2Bi 0.93 2.66 3.572 (3) 166
C4B-H4B...N2Ai 0.93 2.69 3.580 (2) 161
C7B-H7B...O1Bii 0.93 2.43 3.246 (2) 146
C13B-H13D...O1Biii 0.97 2.38 3.324 (2) 163
C13B-H13C...O2Aiv 0.97 2.57 3.435 (2) 148
C13A-H13A...O1Ai 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[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: WinGX (Farrugia, 1999[Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837-838.]); software used to prepare material for publication: Mercury (Macrae et al., 2006[Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453-457.]), PLATON (Spek, 2009)[Spek, A. L. (2009). Acta Cryst. D65, 148-155.] and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).


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

Bore, L., Honda, T., Gribble, G. W., Lork, E. & Jasinski, J. P. (2002). Acta Cryst. C58, o199-o200.  [CSD] [CrossRef] [details]
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.  [CrossRef] [ChemPort] [ISI]
Dinkova-Kostova, A. T., Talalay, P., Sharkey, J., Zhang, Y., Holtzclaw, W. D., Xiu Jun Wang, X. J., David, E., Schiavoni, K. H., Finlayson, S., Dale, F., Mierke, D. F. & Honda, T. (2010). J. Biol. Chem. 285, 33747-33755.  [ChemPort] [PubMed]
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837-838.  [CrossRef] [ChemPort] [details]
Gavezzotti, A. (2008). CrystEngComm, 10, 389-398.  [ChemPort]
Honda, T., Sundararajan, C., Yoshizawa, H., Su, X., Honda, Y., Liby, K. T., Sporn, M. B. & Gribble, G. W. (2007). J. Med. Chem. 50, 1731-1734.  [ISI] [CrossRef] [PubMed] [ChemPort]
Honda, T., Yoshizawa, H., Sundararajan, C., David, E., Lajoie, M. J., Favaloro, F. G. Jr, Janosik, T., Su, X., Honda, Y., Roebuck, B. D. & Gribble, G. W. (2011). J. Med. Chem. 54, 1762-1778.  [ISI] [CrossRef] [ChemPort] [PubMed]
Liby, K., Yore, M. M., Roebuck, B. D., Baumgartner, K. J., Honda, T., Sundararajan, C., Yoshizawa, H., Gribble, G. W., Williams, C. R., Risingsong, R., Royce, D. B., Dinkova-Kostova, A. T., Stephenson, K. K., Egner, P. A., Yates, M. S., Groopman, J. D., Kensler, T. W. & Sporn, M. B. (2008). Cancer Res. 68, 6727-6732.  [ISI] [CrossRef] [PubMed] [ChemPort]
Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453-457.  [ISI] [CrossRef] [ChemPort] [details]
Marcos, I. S., Cubillo, M. A., Moro, R. F., Carballares, S., Díez, D., Basabe, P., Llamazares, C. F., Benéitez, A., Sanz, F., Broughton, H. B. & Urones, J. G. (2005). Tetrahedron, 61, 977-1003.  [ISI] [CSD] [CrossRef] [ChemPort]
Oxford Diffraction (2010). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [details]
Spek, A. L. (2009). Acta Cryst. D65, 148-155.  [ISI] [CrossRef] [details]
Steed, J. W. (2003). CrystEngComm, 5, 169-179.  [ISI] [CrossRef] [ChemPort]
Steiner, T. (2000). Acta Cryst. B56, 673-676.  [ISI] [CrossRef] [ChemPort] [details]
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.  [ISI] [CrossRef] [ChemPort] [details]
Zheng, S., Laximi, Y. R. S., David, E., Dinkova-Kostova, A. T., Shiavoni, K. H., Ren, Y., Zheng, Y., Trevino, I., Bumeister, R., Ojima, I., Wigley, W. C., Bliska, J. B., Mierke, D. F. & Honda, T. (2012). J. Med. Chem. 55, 4837-4846.  [ISI] [CrossRef] [ChemPort] [PubMed]


Acta Cryst (2012). E68, o3095-o3096   [ doi:10.1107/S1600536812041244 ]

This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.