Synthesis of heterobifunctional crosslinking reagents: ω-(N-Maleimido)-alkanoic acid hydrazides

ω-(N-Maleimido)alkanoic acid hydrazides (6a-c) with C₁₁, C₇ and C₅ alkyl arms have been synthesized by novel method. The method involves the reaction between maleic anhydride and ω-aminoalkanoic acids (2) to get maleamic acids (3) which are in turn cyclized to ω-(N̄-maleimido)alkanoic acids (4) using fused sodium acetate and acetic anhydride. These maleimidoalkanoic acids are activated and then converted in situ into their N-2-t-butyloxycarbonyl hydrazides (5) from which the t-butyl-based protecting group is cleaved without damage to the maleimide molety to obtain the title compounds.