Competitive Reactions During Amine Addition to cis-Aconityl Anhydride

Abstract

Amine addition to cis-aconityl anhydride has been used to prepare monomers needed to make water-soluble polymers that are being developed for biomedical applications. Unfortunately competitive decarboxylation, double bond isomerization, and hydrolysis reactions of cis-aconityl anhydride have been observed during monomer synthesis. Since cis-aconityl anhydride has also been used for bioconjugation applications, these deleterious side reactions should be accounted for. Reactions and product profiles of cis-aconityl anhydride with amines and amino acids in aqueous and organic media are described. The side reactions could be avoided with weakly nucleophilic aromatic amines and by the interfacial reaction of glycine with cis-aconityl anhydride.