Amines citraconic anhydride

Citraconic anhydride (or 2-methylmaleic anhydride) is a derivative of maleic anhydride that is even more reversible after acylation than maleylated compounds. At alkaline pH values (pH 7-8) the reagent effectively reacts with amine groups to form amide linkages and a terminal carboxylate. However, at acid pH (3-4), these bonds rapidly hydrolyze to release citraconic acid and free the amine (Figure 1.86) (Dixon and Perham, 1968 Habeeb and Atassi, 1970 Klapper and Klotz, 1972 Shetty and Kinsella, 1980). Thus, citraconic anhydride has been used to temporarily block amine groups while other parts of a molecule are undergoing derivatization. Once the modification is complete, the amines then can be unblocked to create the original structure. 

Figure 1.86 Citraconic anhydride can be used to block amine groups reversibly. The amide bond derivative is unstable to acidic conditions.

Add a quantity of citraconic anhydride to the reaction medium to provide at least a 5-10 molar excess of reagent over the amount of amines to be modified. Even greater molar excesses may be required for total blocking of all the amines of some proteins. 

BA BuE-PA BE-HET BE-HHPA BE-MA BE-PA BE-SA CA CHX DMA DMBA DY 062 GA HEB HHPA HMTA MA MTHPA NMA benzoic acid monobutylester of phthalic acid monobenzylester of hexachloroendomethylenetetrahydrophthalic acid monobenzylester of hexahydrophthalic acid monobenzylester of maleic acid monobenzylester of phthalic acid monobenzylester of succinic acid citraconic anhydride cyclohexanol N,N-dimethylaniline dimethylbenzylamine high boiling tertiary amine (Ciba Geigy AG) gjptaric anhydride 2-hydroxy-4-(2,3-epoxypropoxy)benzophenone hexahydrophthalic anhydride hexamethylenetetramine maleic anhydride methyltetrahydrophthalic anhydride nadic methyl anhydride (methylbicyclo[2.2.1]heptene-2,3-dicarboxylic anhydride isomers)... 

Habeeb and Atassi, 1970 Shetty and Kinsella, 1980). Thus, citraconic anhydride is useful in temporarily blocking amine groups while other parts of a molecule are undergoing derivatization. Once the modification is complete, the amines can be then unblocked to create the original structure. See Section 4.2 for additional information and a protocol for modification of proteins with citraconic anhydride. 

Functionalized PPE may he prepared hy allowing PPE to react with a species that contains both a C=C bond and a reactive moiety, such as hydroxyl, acid, anhydride, amine, imide, epoxy, etc. Examples of species of the acid and anhydride type include maleic anhydride, fumaric acid, and citraconic anhydride. ... 

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