N-aryl benzisoselenazolones – synthesis, transformations and antioxidant activity

The applicability of organoselenium compounds in medicinal chemistry arises from their unique biological properties, among which the antioxidant activity seems to be the leading one. Since ebselen (N-phenyl-1,2-benzisoselenazol-3(2H)-one) has been proven to mimic the activity of the antioxidant enzyme glutathione peroxidase GPx, the search for more effective peroxide scavengers has become a ‘hot topic’ in this field of research. Herein, we present the synthesis of N-aryl ebselen derivatives, bearing additional electron donating or electron withdrawing groups in the N-phenyl ring, by two methods: (a) reaction of N-substituted o-iodobenzamides with lithium diselenide, (b) synthesis based on the formation of 2,2-diselenobis(benzoic acid), followed by the conversion to corresponding dichloride and further reaction with amine. Significant improvements in these methodologies are highlighted. All obtained ebselen derivatives were further converted to corresponding diselenides by the treatment with sodium borohydride. The antioxidant potential of the obtained selenium derivatives and conclusions concerning the activity-structure relation are presented.