Convenient Synthesis, Characterization and GPx‐Like Catalytic Activity of Novel Ebselen Derivatives

<jats:title>Abstract</jats:title><jats:p>The synthesis and characterization of benzisochalcogenazolones (ebselen derivatives <jats:bold>16</jats:bold>−<jats:bold>21</jats:bold>) is described. The synthesis of <jats:bold>16</jats:bold>−<jats:bold>21</jats:bold> was achieved by treating the bromo precursors <jats:bold>11</jats:bold>−<jats:bold>13</jats:bold> with an appropriate dilithium dichalcogenide. The synthesis of benzisoselenazolones <jats:bold>16</jats:bold> and <jats:bold>18</jats:bold> was also accomplished by an alternative route, that is, by treating the corresponding methoxymethyl selenides <jats:bold>22</jats:bold> and <jats:bold>23</jats:bold> with 1 equiv. of bromine. The synthesis of methoxymethyl selenides <jats:bold>22</jats:bold> and <jats:bold>23</jats:bold> was accomplished by lithiation of the bromo precursors followed by treatment with bis(methoxymethyl) diselenide. The benzisoselenazolones <jats:bold>16</jats:bold> and <jats:bold>17</jats:bold> were characterized by single‐crystal X‐ray techniques. The GPx‐like catalytic activities of compounds <jats:bold>16</jats:bold>−<jats:bold>18</jats:bold> and <jats:bold>21</jats:bold> were determined by using the coupled reductase assay. Compound <jats:bold>16</jats:bold> was found to be less active than ebselen <jats:bold>8</jats:bold> whereas compounds <jats:bold>17</jats:bold> and <jats:bold>18</jats:bold> were more active than ebselen in this assay. Compound <jats:bold>21</jats:bold> showed a 1.5‐fold higher activity than its selenium analogue <jats:bold>17</jats:bold>. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)</jats:p>