(11R)-13-Dimethyl­ammonio-11,13-dihydro-4,5-epoxy­costunolide semifumarate

Neelakantan, S.; Parkin, S.; Crooks, P.A.

doi:10.1107/S1600536809021941

Volume 65
Part 7
Page o1569
July 2009

Received 11 May 2009
Accepted 9 June 2009
Online 13 June 2009

Key indicators
Single-crystal X-ray study
T = 90 K
Mean (C-C) = 0.002 Å
R = 0.027
wR = 0.069
Data-to-parameter ratio = 14.0
Details

(11R)-13-Dimethylammonio-11,13-dihydro-4,5-epoxycostunolide semifumarate

Sundar Neelakantan,^a Sean Parkin ^b and Peter A. Crooks ^a ^*

^aDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA, and ^bDepartment of Chemistry, University of Kentucky, Lexington, KY 40506, USA
Correspondence e-mail: pcrooks@email.uky.edu

Crystals of the title salt, C₁₇H₂₈NO₃⁺·C₄H₃O₄^-, were obtained by reacting parthenolide with dimethylamine followed by conversion of the amine adduct into a water-soluble fumarate salt. Subsequent crystallization of the fumarate salt from water afforded colorless orthorhombic crystals. The amine addition is highly stereospecific yielding exclusively a single diastereomer with R-configuration at the newly formed C-11 chiral carbon. In the crystal, intermolecular O-HO and N-HO hydrogen bonds help to establish the packing.

Related literature

Parthenolide (PTL) is a naturally occurring sesquiterpene lactone used in the treatment of fever, migraine headaches, rheumatoid arthritis, and also as an anti-inflammatory agent (Heptinstall et al. (1988). For the potent anti-tumor and cytotoxic properties of PTL, see: Crooks et al. (2007). The absolute stereochemistry of the C-11 chiral carbon is typical of such amine adducts of parthenolide, see: Nasim et al. (2007a,b). For bond-length data, see: Allen et al. (1987).

Experimental

Crystal data

C₁₇H₂₈NO₃⁺·C₄H₃O₄^-
M_r = 409.47
Orthorhombic, P 2₁ 2₁ 2₁
a = 6.3164 (1) Å
b = 15.1650 (2) Å
c = 22.0028 (3) Å
V = 2107.61 (5) Å³
Z = 4
Cu K radiation
= 0.80 mm^-1
T = 90 K
0.26 × 0.20 × 0.10 mm

Data collection

Bruker X8 Proteum diffractometer
Absorption correction: multi-scan (SADABS in APEX2; Bruker-Nonius, 2006) T_min = 0.788, T_max = 0.924
16991 measured reflections
3762 independent reflections
3640 reflections with I > 2(I)
R_int = 0.041

Refinement

R[F² > 2(F²)] = 0.027
wR(F²) = 0.069
S = 1.04
3762 reflections
268 parameters
H-atom parameters constrained
_max = 0.20 e Å^-3
_min = -0.14 e Å^-3
Absolute structure: Flack (1983), 1525 Friedel pairs
Flack parameter: -0.01 (4)

Table 1
Hydrogen-bond geometry (Å, °)

D-HA	D-H	HA	DA	D-HA
N1-H1NO6	0.93	1.83	2.7563 (14)	172
O4-H4O6ⁱ	0.84	1.73	2.5544 (13)	169
Symmetry code: (i) x-1, y, z.

Data collection: APEX2 (Bruker-Nonius, 2006); cell refinement: SAINT (Bruker-Nonius, 2006); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 and local procedures.

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HG2516 ).

Acknowledgements

This research work was supported by the Kentucky Lung Cancer Research Program.

References

Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1-19.
Bruker-Nonius (2006). APEX2 and SAINT. Bruker-Nonius AXS Inc., Madison, Wisconsin, USA.
Crooks, P. A., Jordan, C. T. & Wei, X. (2007). US Patent No. 7 312 242.
Flack, H. D. (1983). Acta Cryst. A39, 876-881.
Heptinstall, S., Groenewegen, W. A., Spangenberg, P. & Lösche, W. (1988). Folia Haematol. Int. Mag. Klin. Morphol. Blutforsch. 115, 447-449.
Nasim, S., Parkin, S. & Crooks, P. A. (2007a). Acta Cryst. E63, o3922.
Nasim, S., Parkin, S. & Crooks, P. A. (2007b). Acta Cryst. E63, o4274.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.

organic compounds