New protein reagents. Synthesis and properties of halogenated maleimides and isomaleimides.

The title compounds were investigated as examples of potential hetero-bifunctional protein reagents having an electrophilic moiety in addition to a maleimide or isomaleimide ring. The synthesis of such products by cyclization of the corresponding maleamic acids gives lower yields in the maleimide than in the isomaleimide series, especially when the second function is labile, owing to the more drastic reaction conditions necessary to form the symmetric isomer. On the other hand, a comparison of the isomeric imides showed that despite some differences in reactivity, isomaleimides can be used instead of maleimides for chemical modification of proteins. Therefore, if the synthesis of new maleimide reagents containing a second fragile functional group is difficult, they can be designed in the isoimide form.