A Novel Camphor-Derived Selenenamide That Acts as a Glutathione Peroxidase Mimetic

• Published in: Journal of the American Chemical Society Vol. 119; no. 9; pp. 2079 - 2083
• Main Authors: Back, Thomas G, Dyck, Brian P
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 05.03.1997; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; ANTIOXIDANT ACTIVITY; OXIDATION; THIOLS; ACTIVE ORGANOSELENIUM COMPOUND; LIPID-PEROXIDATION; MECHANISM; PZ-51 EBSELEN; MODEL; DERIVATIVES; SELENO-ORGANIC COMPOUND
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja963602k

A novel cyclic selenenamide 6 was prepared from the corresponding amido-substituted diselenide 5 by brominolysis and treatment with silver triflate. The selenenamide promotes the oxidation of phenylmethanethiol to the corresponding disulfide with tert-butyl hydroperoxide. It functions by reacting with the thiol to afford selenenyl sulfide 8, which undergoes further attack by the thiol to produce dibenzyl disulfide and selenol 9. The latter compound is oxidized by the hydroperoxide to the selenenic acid 10, which in turn reacts with additional thiol, thus regenerating the selenenyl sulfide and forming water as the byproduct. The original selenenamide therefore acts as a procatalyst in this process and is not regenerated, whereas the selenenyl sulfide is the true catalyst. The selenenyl sulfide was isolated in the absence of the hydroperoxide and was fully characterized. The selenol was not observed in the catalytic cycle, but its transient formation was supported by a crossover experiment in which selenenyl sulfide 8 underwent thiol interchange with (4-methoxyphenyl)methanethiol. The catalytic cycle strongly resembles the mechanism by which the selenium-containing enzyme glutathione peroxidase catalyzes the destruction of hydroperoxides in vivo through the concomitant oxidation of glutathione to the corresponding disulfide.