Aspartame - Chemistry

Chemistry

Aspartame is a methyl ester of the dipeptide of the natural amino acids -aspartic acid and -phenylalanine. Under strongly acidic or alkaline conditions, aspartame may generate methanol by hydrolysis. Under more severe conditions, the peptide bonds are also hydrolyzed, resulting in the free amino acids.

While known aspects of synthesis are covered by patents, many details are proprietary. Two approaches to synthesis are used commercially. In the chemical synthesis, the two carboxyl groups of aspartic acid are joined into an anhydride, and the amino group is protected by a compound that will prevent further reactions of that group. Phenylalanine is methylated and combined with the N-protected aspartic anhydride, then the blocking group is removed from aspartic acid by acid hydrolysis. The drawback of this technique is that a byproduct, the bitter tasting β-form, is produced when the wrong carboxyl group from aspartic acid links to phenylalanine. A process using an enzyme from Bacillus thermoproteolyticus to catalyze the condensation of the chemically altered amino acids will produce high yields without the β-form byproduct. A variant of this method, which has not been used commercially, uses unmodified aspartic acid, but produces low yields. Methods for directly producing aspartyl-phenylalanine by enzymatic means, followed by chemical methylation, have also been tried, but not scaled for industrial production.