Synthesis of intramolecularly coordinated cyclic selenenate/thioselenenate esters and their glutathione peroxidase-like activity

Abstract

The syntheses and characterization of selenenate esters, thioselenenate ester and related derivatives are described. The reactions of <i style="">n</i>-butyl-4-<i style="">tert</i>-2,6-di(formyl)phenyl selenide (<b style="">23</b>) or bis(2,6-diformyl-4-<i style="">tert</i>-butylphenyl)diselenide (<b style="">24</b>) with bromine affords a new selenenate ester, 5-<i style="">tert</i>-butyl-7-(formyl)benzoxaselenol-3-one (<b style="">25</b>), stabilized by <i style="">ortho</i>-formyl group along with 3,3′-oxybis(5-<i style="">tert</i>-butyl-3H-benzo[c][1,2]oxoselenole-7-carbaldehyde) (<b style="">16</b>). Oxidation of (<b style="">25</b>) with H₂O₂ gives 5-<i style="">tert</i>-butyl-7-(carboxylic)benzoxaselenol-3-one-Se-oxide (<b style="">26</b>). However, the direct oxidation of (<b style="">23</b>) with H₂O₂ affords 5-<i style="">tert</i>-butyl-7-(butylcarboxylate)benzoxaselenol-3-one (<b style="">27</b>). The synthesis of 5-<i style="">tert</i>-butyl-7-(methylcarboxylate) benzothia- selenol-3-one (<b style="">28</b>) has been accomplished by the reaction of (<b style="">26</b>) with thionyl chloride (SOCl₂) with a catalytic amount of N, N-dimethylformamide. Attempted thionation of 7-nitro-1,2-benzisoselenole(3<i style="">H</i>)-Se-oxide (<b style="">20</b>) leads to the isolation of bis(2-chloromethyl-6-nitrophenyl)diselenide (<b style="">29</b>). The presence of intramolecular secondary Se···O interactions in all the esters is confirmed by single crystal X-ray diffraction studies and computational studies. Glutathione peroxidase-like activity of (<b style="">16</b>), (<b style="">25</b>)-(<b style="">29</b>) has been determined by the coupled reductase assay.