Organocatalytic-racemization reaction elucidation of aspartic acid by density functional theory

Aldehydes and carboxylic acids are widely used as catalysts for efficient racemization process of amino acids. However, the detailed reaction mechanism remains unclear. This work aims to clarify the racemization mechanism of aspartic acid (Asp) catalyzed by salicylaldehyde and acetic acid by using computational approaches. Density functional theory was used to obtain the structures and relative energies of 10 intermediates and five transition states, thus characterizing the main stages of the reaction. The calculated energy diagram shows that the dehydration step has the highest energy barrier, followed by the reaction step to change the chirality of Asp, which is a crucial process for racemization. In the dehydration reaction, water molecules can induce a remarkable decrease in the required energy.