Diselenides and allyl selenides as glutathione peroxidase mimetics. Remarkable activity of cyclic seleninates produced in situ by the oxidation of allyl omega-hydroxyalkyl selenides.
A series of aliphatic diselenides and selenides containing coordinating substituents was tested for glutathione peroxidase (GPx)-like catalytic activity in a model system in which the reduction of tert-butyl hydroperoxide with benzyl thiol to afford dibenzyl disulfide and tert-butyl alcohol was performed under standard conditions and monitored by HPLC. Although the diselenides showed generally poor catalytic activity, allyl selenides proved more effective. In particular, allyl 3-hydroxypropyl selenide (25) rapidly generated 1,2-oxaselenolane Se-oxide (31) in situ by a series of oxidation and [2,3]sigmatropic rearrangement steps. The remarkably active cyclic seleninate 31 proved to be the true catalyst, reacting with the thiol via a postulated mechanism in which the thioseleninate 32 is first produced, followed by further thiolysis to selenenic acid 33 and oxidation-dehydration to regenerate 31. In contrast to catalysis with GPx, formation of the corresponding selenenyl sulfide 34 comprises a competing deactivation pathway in the catalytic cycle of 31, as a separate experiment revealed that authentic 34 was a much less effective catalyst than 31. 1,2-Oxaselenane Se-oxide (37), the six-membered homologue of 31, was formed similarly from allyl 4-hydroxybutyl selenide (26), but proved a less effective catalyst than 31. Compounds 31 and 37 are the first examples of unsubstituted monocyclic seleninate esters.
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Thomas G
TG
Department of Chemistry, University of Calgary, Calgary, Alberta, Canada, T2N 1N4. tgback@ucalgary.ca
Moussa
Ziad
Z
D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000737:chemistry* / Q000378:metabolism; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction
D016566:Organoselenium Compounds; D005979:Glutathione Peroxidase