Abstract
Cyclic seleninate esters function as mimetics of the antioxidant selenoenzyme glutathione peroxidase. They catalyze the reduction of harmful peroxides with thiols, which are converted to disulfides in the process. The possibility that the seleninate esters could also catalyze the further oxidation of disulfides to thiolsulfinates and other overoxidation products under these conditions was investigated. This has ramifications in potential medicinal applications of seleninate esters because of the possibility of catalyzing the unwanted oxidation of disulfide-containing spectator peptides and proteins. A variety of aryl and alkyl disulfides underwent facile oxidation with hydrogen peroxide in the presence of catalytic benzo-1,2-oxaselenolane Se-oxide affording the corresponding thiolsulfinates as the principal products. Unsymmetrical disulfides typically afforded mixtures of regioisomers. Lipoic acid and N,N′-dibenzoylcystine dimethyl ester were oxidized readily under similar conditions. Although isolated yields of the product thiolsulfinates were generally modest, these experiments demonstrate that the method nevertheless has preparative value because of its mild conditions. The results also confirm the possibility that cyclic seleninate esters could catalyze the further undesired oxidation of disulfides in vivo.
Highlights
The selenoenzyme family of glutathione peroxidases (GPx) catalyzes the reduction of harmful hydrogen peroxide and lipid hydroperoxides by the stoichiometric reductant glutathione
The design and synthesis of small-molecule selenium compounds that emulate the function of GPx has proven of interest as a means to suppress oxidative stress that is implicated in a variety of disease states [4,5,6,7,8,9]
In our previous work [19], we had observed that the presence of trifluoroacetic acid (TFA) accelerated the oxidations shown in Scheme 2, while basic conditions suppressed them
Summary
The selenoenzyme family of glutathione peroxidases (GPx) catalyzes the reduction of harmful hydrogen peroxide and lipid hydroperoxides by the stoichiometric reductant glutathione. This process provides protection to living organisms against oxidative stress caused by peroxides and other reactive oxygen species they generate, such as the superoxide radical anion and the hydroxyl radical [1,2,3]. Seleninate ester 1 and its congeners effectively catalyze the in vitro conversion of benzyl thiol to the corresponding disulfide with hydrogen peroxide, as shown in Scheme 1. In the course of this work, we recently observed that in the case of certain related seleninate esters, the concentration of the disulfide reached a maximum at ca
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