5292
L. Robertson, R.C. Hartley / Tetrahedron 65 (2009) 5284–5292
5461–5463; (c) Gigmes, D.; Gaudel-Siri, A.; Marque, S. R. A.; Bertin, D.; Tordo,
P.; Astolfi, P.; Greci, L.; Rizzoli, C. Helv. Chim. Acta 2006, 89, 2312–2326; (d)
Sueishi, Y.; Yoshioka, D.; Yoshioka, C.; Yamamoto, S.; Kotake, Y. Org. Biomol.
Chem. 2006, 4, 896–901.
7. (a) Gamliel, A.; Afri, M.; Frimer, A. A. Free Radical Biol. Med. 2008, 44, 1394–
1405; (b) Bardelang, D.; Charles, L.; Finet, J. P.; Jicsinszky, L.; Karoui, H.; Marque,
S. R. A.; Monnier, V.; Rockenbauer, A.; Rosas, R.; Tordo, P. Chem.dEur. J. 2007, 13,
9344–9354; (c) Caldwell, S. T.; Quin, C.; Edge, R.; Hartley, R. C. Org. Lett. 2007, 9,
3499–3502.
of nitrone 44). Data derived for nitrone 44: dH (400 MHz, CDCl3):
0.87 (3H, t, J 7.1 Hz, CH3), 1.29–1.34 (4H, m, 2ꢁCH2), 1.40–1.47 (2H,
m, CH2), 1.56 (9H, s, 3ꢁCH3), 1.70–1.77 (2H, m, CH2), 3.45 (2 h, br s,
NH2), 3.88 (2H, t, J 6.4 Hz, CH2), 6.64–6.69 (2H, m, H-5 and H-6),
8.01 (1H, s, CH]N), 8.78 (1H, d, J 2.6 Hz, H-2)]. Material was carried
on to next stage with no further purification or analysis.
8. Recent examples include: (a) Durand, G.; Poeggeler, B.; Boeker, J.; Raynal, S.;
Polidori, A.; Pappolla, M. A.; Hardeland, R.; Pucci, B. J. Med. Chem. 2007, 50,
3976–3979; (b) Kim, S.; Vilela, G. V. M. de. A.; Bouajila, J.; Dias, A. G.; Cyrino, F.
Z. G. A.; Bouskela, E.; Costa, P. R. R.; Nepveu, F. Bioorg. Med. Chem. 2007, 15,
3572–3578; (c) Asanuma, T.; Yasui, H.; Inanami, O.; Waki, K.; Takahashi, M.;
Iizuka, D.; Uemura, T.; Durand, G.; Polidori, A.; Kon, Y.; Pucci, B.; Kuwabara, M.
Chem. Biodivers. 2007, 4, 2253–2267; (d) Sklavounou, E.; Hay, A.; Ashraf, N.;
Lamb, K.; Brown, E.; MacIntyre, A.; George, W. D.; Hartley, R. C.; Shiels, P. G.
Biochem. Biophys. Res. Commun. 2006, 347, 420–427; (e) Ortial, S.; Durand, G.;
Poeggeler, B.; Polidori, A.; Pappolla, M. A.; Bo¨ker, J.; Hardeland, R.; Pucci, B.
J. Med. Chem. 2006, 49, 2812–2820.
9. (a) Hardy, M.; Chalier, F.; Ouari, O.; Finet, J. P.; Rockenbauer, A.; Kalyanaraman,
B.; Tordo, P. Chem. Commun. 2007, 1083–1085; (b) Hardy, M.; Rockenbauer, A.;
Vasquez-Vivar, J.; Felix, C.; Lopez, M.; Srinivasan, S.; Avadhani, N.; Tordo, P.;
Kalyanaraman, B. Chem. Res. Toxicol. 2007, 20, 1053–1060; (c) Xu, Y.; Kalya-
naraman, B. Free Radical Res. 2007, 41, 1–7; (d) Murphy, M. P.; Echtay, K. S.;
Blaikie, F. H.; Asin-Cayuela, J.; Cocheme, H. M.; Green, K.; Buckingham, J. A.;
Taylor, E. R.; Hurrell, F.; Hughes, G.; Miwa, S.; Cooper, C. E.; Svistunenko, D. A.;
Smith, R. A.; Brand, M. D. J. Biol. Chem. 2003, 278, 48534–48545.
10. Murphy, M. P.; Smith, R. A. Annu. Rev. Pharmacol. Toxicol. 2007, 47, 629–656.
11. For example: (a) Casey, J. R.; Morgan, P. E.; Vullo, D.; Scozzafava, A.; Mas-
trolorenzo, A.; Supuran, C. T. J. Med. Chem. 2004, 47, 2337–2347; (b) Pastor-
ekova, S.; Casini, A.; Scozzafava, A.; Vullo, D.; Pastorek, J.; Supuran, C. T. Bioorg.
Med. Chem. 2004, 14, 869–874; (c) Springer, D. M.; Luh, B.-Y.; Goodrich, J. T.;
Bronson, J. J. Bioorg. Med. Chem. 2003, 11, 281–292; Springer, D. M.; Luh, B.-Y.;
Goodrich, J. T.; Bronson, J. J. Bioorg. Med. Chem. 2003, 11, 265–280; (d) Springer,
D. M.; Luh, B.-Y.; Bronson, J. J. Bioorg. Med. Chem. Lett. 2001, 11, 797–802.
12. Koya, K.; Li, Y.; Wang, H.; Ukai, T.; Tatsuta, N.; Kawakami, M.; Shishido, T.; Chen,
L. B. Cancer Res. 1996, 56, 538–543.
2.22.
nitrone 45
a-(5-Amino-2-dodecyloxyphenyl)-N-tert-butyl-
N-tert-Butyl-a-(2-dodecyloxy-5-nitrophenyl)nitrone 43 (563 mg,
1.38 mmol) and palladium hydroxide (20% on carbon, 48 mg,
5 mol %) were dissolved in ethyl acetate (7.5 mL). The solution
was flushed with hydrogen then placed under a hydrogen at-
mosphere and stirred at room temperature for 50 min. The
catalyst was removed by filtration and the solution was con-
centrated in vacuo to give 45 as a brown solid (517 mg, 99%). dH
(400 MHz, CDCl3): 0.87 (3H, t, J 6.3 Hz, CH3), 1.21–1.34 (16H, m,
8ꢁCH2), 1.42–1.47 (2H, m, CH2), 1.59 (9H, s, 3ꢁCH3), 1.73–1.78
(2H, m, CH2), 3.40 (2H, br s, NH2), 3.91 (2H, t, J 6.4 Hz, CH2),
6.69–6.73 (2H, m, H-5 and H-6), 8.05 (1H, s, CH]N), 8.82 (1H,
d, J 2.3 Hz, H-2). The material was carried onto next stage with
no further purification or analysis.
2.23. EPR spectroscopy
Iron(II) sulfate (100
drogen peroxide (100
to a solution of the nitrone 13,14 or 15 in DMSO (100
m
L of a 1 mM aqueous solution) and hy-
L of a 1 mM aqueous solution) were added
L of a 2.5 mM
m
m
13. Novgorodov, S. A.; Szule, Z. M.; Luberto, C.; Jones, J. A.; Bielawski, J.; Bielawski,
A.; Hannun, Y. A.; Obeid, L. M. J. Biol. Chem. 2005, 280, 16096–16105.
14. Janzen, E. G.; Dudley, R. L.; Shetty, R. V. J. Am. Chem. Soc. 1979, 101, 243–245.
15. Janzen, E. D.; Kotake, Y.; Hinton, R. D. Free Radical Biol. Med. 1992, 12,
169–173.
16. Janzen, E. G.; West, M. S.; Kotake, Y.; DuBose, C. M. J. Biochem. Biophys. Methods
1996, 32, 183–190.
17. Misik, V.; Miyoshi, N.; Riesz, P. J. Phys. Chem. 1995, 99, 3605–3611.
18. Hill, H. A. O.; Thornalley, P. J. Can. J. Chem. 1982, 60, 1528–1531.
19. For an example of trapping radicals in membranes see: Hay, A.; Burkitt, M. J.;
Jones, C. M.; Hartley, R. C. Arch. Biochem. Biophys. 2005, 435, 336–346.
solution in the case of nitrone 13 and a 10 mM solution for nitrones
14 and 15). The solution [0.83 mM nitrone 13 or 3.33 mM nitrone 14
or 15, 0.33 mM hydrogen peroxide, 0.33 mM iron(II) sulfate in
water–DMSO (2:1)] was then immediately transferred to a quartz
flat cell and placed in the EPR spectrometer for analysis. Spectra
were acquired on a Bruker e-scanÔ bench-top EPR machine with
a permanent magnet and a magnetic sweep circuit (centre of
field¼0.345 T, sweep width 25 mT) operating at a frequency of
9.8 GHz (X-band). Acquisition parameters: RG 3.99ꢁ103, 2.76 mW,
MA 0.5 G. Hyperfine couplings were derived from simulations us-
ing WINEPR SimFoniaÔ.
´
20. Sar, C. P.; Hideg, E.; Vass, I.; Hideg, K. Bioorg. Med. Chem. Lett. 1998, 8, 379–384.
21. (a) Schulze, W.; Gutsche, W.; Vater, W.; Oertel, B.; Bo¨hm, K. J.; Unger, E.; Werner,
W. Die Pharmazie 1990, 45, 686–687; (b) Schulze, W.; Gutsche, W.; Jungstan, W.
Arzneim. Forsch. 1967, 17, 605–607; (c) Schulze, W. J. Prakt. Chem. 1962, 17,
24–34.
Acknowledgements
22. Abdallah, M. A.; Andre, J. J.; Biellmann, J.-F. Bioorg. Chem. 1977, 6, 157–163.
23. Hayakawa, K.; Shiomi, D.; Ise, T.; Sato, K.; Takui, T. J. Mater. Chem. 2006, 16,
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24. Cheng, W.-C.; Kurth, M. J. Org. Prep. Proced. Int. 2002, 34, 587–608.
25. Recent examples include: (a) Yamaguchi, I.; Higashi, H.; Shigesue, S.; Shingai, S.;
Sato, M. Tetrahedron Lett. 2007, 48, 7778–7781; (b) Nguyen, T. M.; Sanchez-
Salvatori, M. del. R.; Wypych, J.-C.; Marazano, C. J. Org. Chem. 2007, 72, 5916–
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Gil, R. P. F. Tetrahedron Lett. 2005, 46, 7773–7776.
The Wellcome Trust for funding. SPARC and the BBSRC for the
purchase of the bench-top EPR spectrometer used. Ruth Edge (EPR
National Service, University of Manchester) for advice on EPR
spectra.
References and notes
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