Facile Synthesis of Maleimide Bifunctional Linkers.

The synthesis of maleimide containing derivatives capable of serving as linkers for the conjugation of proteins is described. These compounds differ from previously reported linkers by having multiple sites available for drug attachment. Compounds 3a, 3b, and 3d were synthesized from the corresponding amino alcohols by the addition of two equivalents of t-butyl bromoacetate to a series of amino alcohols followed by the introduction of the maleimide under Mitsunobu reaction conditions and ester hydrolysis.