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Volume 69 
Part 11 
Pages o1709-o1710  
November 2013  

Received 11 September 2013
Accepted 18 October 2013
Online 26 October 2013

Key indicators
Single-crystal X-ray study
T = 90 K
Mean [sigma](C-C) = 0.002 Å
R = 0.027
wR = 0.070
Data-to-parameter ratio = 14.1
Details
Open access

(E)-13-(4-Amino­phen­yl)parthenolide

aDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA,bDepartment of Chemistry, University of Kentucky, Lexington, KY 40506, USA, and cCollege of Medicine, Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Correspondence e-mail: pacrooks@uams.edu

The title compound, C21H25NO3 [systematic name: (3aS,9aR,10aR,10bS,E)-3-[(E)-4-(4-amino­benzyl­idene)-6,9a-dimethyl-3a,4,5,8,9,9a,10a,10b-octa­hydro­oxireno[2',3':9,10]cyclo­deca­[1,2-b]furan-2(3H)-one] was obtained from the reaction of parthenolide [synonym: 4,5-ep­oxy­germacra-1(10),11(13)-dieno-12,6-lactone] with 4-iodo­aniline under Heck reaction conditions. It was identified as the E-isomer (conformation about the exocyclic methyl­idene C=C bond; the conformation about the C=C bond in the ten-membered ring is also E). The mol­ecule is built up from fused ten-, five- (lactone) and three-membered (epoxide) rings with a 4-amino­phenyl group as a substituent. The ten-membered ring displays an approximate chair-chair conformation, while the lactone ring has an envelope conformation with the C atom bonded to the ring O atom as the flap. The dihedral angle between the benzene ring of the 4-amino­phenyl moiety and the lactone ring mean plane is 23.50 (8)°. In the crystal, mol­ecules are linked via N-H...O hydrogen bonds, between the amine group and the lactone and epoxide ring O atoms, forming chains propagating along the b-axis direction. Adjacent chains are linked via C-H...O inter­actions, forming an undulating two-dimensional network lying parallel to the plane (001). The absolute structure of the mol­ecule in the crystal was confirmed by resonance scattering [Flack parameter = 0.03 (3)].

Related literature

For the biological activity of parthenolide, see: Hall et al. (1979[Hall, I. H., Lee, K. H., Starnes, C. O., Sumida, Y., Wu, R. Y., Waddell, T. G., Cochran, J. W. & Gerhart, K. G. (1979). J. Pharm. Sci. 68, 537-542.]). For the biological activity of parthenolide derivatives similar to the title compound, see: Hanson et al. (1970[Hanson, R. L., Lardy, H. A. & Kupchan, S. M. (1970). Science, 168, 378-380.]); Hehner et al. (1998[Hehner, S. P., Heinrich, M., Bork, P. M., Vogt, M., Ratter, F., Lehmann, V., Osthoff, K. S., Dröge, W. & Schmitz, M. L. (1998). J. Biol. Chem. 273, 1288-1297.]); Kupchan et al. (1971[Kupchan, S. M., Eakin, M. A. & Thomas, A. M. (1971). J. Med. Chem. 14, 1147-1152.]); Nasim et al. (2011[Nasim, S., Pei, S. S., Hagen, F. K., Jordan, C. T. & Crooks, P. A. (2011). Bioorg. Med. Chem. 19, 1515-1519.]); Neelakantan et al. (2009[Neelakantan, S., Nasim, S., Guzman, M. L., Jordan, C. T. & Crooks, P. A. (2009). Bioorg. Med. Chem. Lett. 19, 4346-4349.]); Oka et al. (2007[Oka, D., Nishimura, K., Shiba, M., Nakai, Y., Arai, Y., Nakayama, M., Takayama, H., Inoue, H., Okuyama, A. & Nonomura, N. (2007). Int. J. Cancer, 120, 2576-2581.]); Ralstin et al. (2006[Ralstin, M. C., Gage, E. A., Yip-Schneider, M. T., Klein, P. J., Wiebke, E. A. & Schmidt, C. M. (2006). Mol. Cancer Res. 4, 387-399.]); Rodriguez et al. (1976[Rodriguez, E., Towers, G. H. & Mitchell, J. C. (1976). Phytochemistry, 15, 1573-1580.]); Sun et al. (2006[Sun, H.-X., Zheng, Q.-F. & Tu, J. (2006). Bioorg. Med. Chem. 14, 1189-1198.]). For the synthesis and crystal structures of similar mol­ecules, see: Han et al. (2009[Han, C., Barrios, F. J., Riofski, M. V. & Colby, D. A. (2009). J. Org. Chem. 74, 7176-7179.]).

[Scheme 1]

Experimental

Crystal data
  • C21H25NO3

  • Mr = 339.42

  • Orthorhombic, P 21 21 21

  • a = 8.5619 (1) Å

  • b = 11.8846 (2) Å

  • c = 17.7457 (3) Å

  • V = 1805.71 (5) Å3

  • Z = 4

  • Cu K[alpha] radiation

  • [mu] = 0.66 mm-1

  • T = 90 K

  • 0.20 × 0.16 × 0.12 mm

Data collection
  • Bruker X8 Proteum diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996[Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany.]) Tmin = 0.843, Tmax = 0.956

  • 25400 measured reflections

  • 3296 independent reflections

  • 3267 reflections with I > 2[sigma](I)

  • Rint = 0.033

Refinement
  • R[F2 > 2[sigma](F2)] = 0.027

  • wR(F2) = 0.070

  • S = 1.06

  • 3296 reflections

  • 234 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • [Delta][rho]max = 0.13 e Å-3

  • [Delta][rho]min = -0.14 e Å-3

  • Absolute structure: Flack x parameter determined using 1383 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])

  • Absolute structure parameter: 0.03 (3)

Table 1
Hydrogen-bond geometry (Å, °)

D-H...A D-H H...A D...A D-H...A
N1-H1A...O1i 0.94 (2) 2.25 (3) 3.133 (2) 156 (2)
N1-H2B...O2i 0.90 (2) 2.57 (2) 3.077 (2) 116 (2)
C2-H2A...O3ii 0.99 2.63 3.372 (2) 132
Symmetry codes: (i) x, y-1, z; (ii) [x+{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+1].

Data collection: APEX2 (Bruker, 2006[Bruker (2006). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2006[Bruker (2006). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.


Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SU2647 ).


Acknowledgements

This work was supported by NIH/NCI [grant No. CA158275].

References

Bruker (2006). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
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Han, C., Barrios, F. J., Riofski, M. V. & Colby, D. A. (2009). J. Org. Chem. 74, 7176-7179.  [CSD] [CrossRef] [PubMed] [ChemPort]
Hanson, R. L., Lardy, H. A. & Kupchan, S. M. (1970). Science, 168, 378-380.  [CrossRef] [ChemPort] [PubMed] [Web of Science]
Hehner, S. P., Heinrich, M., Bork, P. M., Vogt, M., Ratter, F., Lehmann, V., Osthoff, K. S., Dröge, W. & Schmitz, M. L. (1998). J. Biol. Chem. 273, 1288-1297.  [CrossRef] [ChemPort] [PubMed]
Kupchan, S. M., Eakin, M. A. & Thomas, A. M. (1971). J. Med. Chem. 14, 1147-1152.  [CrossRef] [ChemPort] [PubMed] [Web of Science]
Nasim, S., Pei, S. S., Hagen, F. K., Jordan, C. T. & Crooks, P. A. (2011). Bioorg. Med. Chem. 19, 1515-1519.  [CrossRef] [ChemPort] [PubMed]
Neelakantan, S., Nasim, S., Guzman, M. L., Jordan, C. T. & Crooks, P. A. (2009). Bioorg. Med. Chem. Lett. 19, 4346-4349.  [CrossRef] [PubMed] [ChemPort]
Oka, D., Nishimura, K., Shiba, M., Nakai, Y., Arai, Y., Nakayama, M., Takayama, H., Inoue, H., Okuyama, A. & Nonomura, N. (2007). Int. J. Cancer, 120, 2576-2581.  [Web of Science] [CrossRef] [PubMed] [ChemPort]
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.  [CrossRef] [ChemPort] [IUCr Journals]
Ralstin, M. C., Gage, E. A., Yip-Schneider, M. T., Klein, P. J., Wiebke, E. A. & Schmidt, C. M. (2006). Mol. Cancer Res. 4, 387-399.  [Web of Science] [CrossRef] [PubMed] [ChemPort]
Rodriguez, E., Towers, G. H. & Mitchell, J. C. (1976). Phytochemistry, 15, 1573-1580.  [CrossRef] [ChemPort] [Web of Science]
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [ChemPort] [IUCr Journals]
Sun, H.-X., Zheng, Q.-F. & Tu, J. (2006). Bioorg. Med. Chem. 14, 1189-1198.  [CrossRef] [PubMed] [ChemPort]


Acta Cryst (2013). E69, o1709-o1710   [ doi:10.1107/S1600536813028730 ]

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