7450
M. Messali et al. / Tetrahedron Letters 48 (2007) 7448–7451
4. (a) Dereu, N.; Graf, E. Drugs Future 1984, 9, 741; (b)
Parnham, M.; Leyck, S.; Dereu, N.; Winkelmann, J.;
Graf, E. Adv. Inflamm. Res. 1985, 10, 397.
5. (a) Cantineau, R.; Tihange, G.; Plenevaux, A.; Christia-
ens, L.; Guillaume, M.; Welter, A.; Dereu, N. Labelled
Comp. Radiopharm. 1986, 23, 59; (b) Wendel, A.; Faussel,
M.; Sarfadi, M.; Tiegs, G.; Otter, R. Biochem. Pharmacol.
1984, 33, 3241.
Selenide 11a was nitrosated with NaNO2, CH3CO2H
resulting in a good yield of oxime 12a.22 The oxi-
mination of ketones 11b–c was difficult using similar
conditions, however, when this reaction was performed
using (n-BuNO2, HCl) and 2-ethoxyethanol as a sol-
vent,22 oximes 12b–c were successfully obtained.23
Oximes 12a–c were cyclized into 4H-benzo[e]-1,2-selena-
zin-4-ones 6a–c24 via Se-demethylation using trimethyl-
silyl polyphosphate (PPSE).25,26
6. (a) Parnham, M. J.; Graf, E. Biochem. Pharmacol. 1987,
36, 3095, and references cited therein; (b) Narayanaswami,
V.; Sies, H. Free Rad. Res. Commun. 1990, 10, 237, and
references cited therein; (c) John, N. J.; Terlinden, R.;
Fischer, H.; Evers, M.; Sies, H. Chem. Res. Toxicol. 1990,
3, 199.
7. For a list of potential medicinal applications of ebselen,
see: Fong, M. C.; Schiesser, C. H. Tetrahedron Lett. 1995,
36, 7329, and references cited therein.
8. (a) Fischer, H.; Dereu, N. Bull. Soc. Chim. Belg. 1987, 96,
757; (b) Glass, R. S.; Farooqui, F.; Sabahi, M.; Ehler, K.
W. J. Org. Chem. 1989, 54, 1092.
9. (a) Parnham, M. J.; Biedermann, J.; Bittner, Ch.; Dereu,
N.; Leyck, S.; Wetzig, H. Agents Actions. 1989, 27, 306;
(b) Renson, M.; Dereu, N. J. Pharm. Belg. 1990, 45, 322.
10. Wilson, S. R.; Zucker, P. A.; Huang, R. R. C.; Spector, A.
J. Am. Chem. Soc. 1989, 111, 5936.
11. Reich, H. J.; Jasperse, C. P. J. Am. Chem. Soc. 1987, 109,
5549.
12. Jacquemin, P. V.; Christiaens, L. E.; Renson, M. J.
Tetrahedron Lett. 1992, 33, 3863.
13. Mohsine, A.; Christiaens, L. Heterocycles 1996, 43, 2567.
14. Erdelmeier, I.; Tailhan-Lomont, C.; Yadan, J.-C. J. Org.
Chem. 2000, 65, 8152.
The glutathione peroxidase GPx-like activity and anti-
oxidant properties have been examined for compound
6a and compared to ebselen as a control drug.27 The
kinetic method showed that 6a increased the rate of
the catalytic reduction of H2O2 more than ebselen, as
monitored by the increase of the UV absorption at
305 nm due to the formed diphenyl disulfide (PhSSPh).
However, 6a inhibited the formation of the peroxidized
lipid derived from the reaction of hydroxyl radicals with
linoleic acid using radiation-induced lipid peroxidation.
The evaluation of the antioxidant activity showed
that ebselen and 6a have the same inhibitory effect on
the formation of ABTS radical cation in the ABTS/
MetMb/H2O2 system. On the other hand, according to
EPR spin trapping, 6a exhibited a slightly lower protec-
tion of glutathione from the oxidant attack by the
H2O2/HPR couple compared to ebselen.
The synthesis of novel 1,2-benzoselenazin-4-ones, which
are six-membered homologues of ebselen, has been
achieved. The evaluation of the glutathione peroxi-
dase GPx-like activity and antioxidant properties of
a selected product 6a gave satisfactory results. The
biological tests for the other compounds are under
investigation.
15. Reich, H. J.; Jasperse, C. P. J. Am. Chem. Soc. 1987, 109,
5549.
16. (a) Mugesh, G.; Panda, A.; Singh, H. B.; Punekar, N. S.;
Butcher, R. J. Chem. Commun. 1998, 2227; (b) Mugesh,
G.; Panda, A.; Singh, H. B.; Punekar, N. S.; Butcher, R. J.
J. Am. Chem. Soc. 2001, 123, 839; (c) Wirth, T. Molecules
1998, 3, 164; (d) Zhang, X.; Xu, H.; Dong, Z.; Wang, Y.;
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Wilson, S. R.; Zucker, P. A.; Huang, R.-R. C.; Spector, A.
J. Am. Chem. Soc. 1989, 111, 5936; (f) Zade, S. S.; Singh,
H. B.; Butcher, R. J. Angew. Chem., Int. Ed. 2004, 43,
Acknowledgment
´
4513; (g) Galet, V.; Bernier, J.-L.; Henichart, J.-P.;
The authors would like to thank Dr. Ange Mouithys-
Mickalad for carrying the biological tests.
Lesieur, D.; Abadie, C.; Rochette, L.; Lindenbaum, A.;
Chalas, J.; Renaud de la Faverie, J.-F.; Pfeiffer, B.;
Renard, P. J. Med. Chem. 1994, 37, 2903.
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A.; Powis, G. J. Org. Chem. 1999, 64, 8161; (c) Back, T.
G.; Moussa, Z. J. Am. Chem. Soc. 2002, 124, 12104; (d)
Back, T. G.; Moussa, Z. J. Am. Chem. Soc. 2003, 125,
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21. Characterization of compounds 11a–c: 11a: yellow oil, IR
(NaCl) mmax 1738 (C@O) and 1664 cmÀ1 (C@O); 1H NMR
(300 MHz, CDCl3) d: 1.18 (t, J = 7, 3H), 2.14 (s, 3H), 3.92
(s, 2H), 4.12 (q, J = 7, 2H) 7.22–7.86 (m, 4H); 13C NMR
(125 MHz, CDCl3) d: 7.1 (CH3), 14.8 (CH3), 47.2 (CH2),
62.1 (CH2), 124.9 (C), 126.2 (CH), 127.5 (CH), 131.2
(CH), 133.4 (CH) 140.9 (C), 168.1 (C@O), 193.4 (C@O);