Aspartame Decomposition and Epimerization in the Diketopiperazine and Dipeptide Products as a Function of pH and Temperature

Article abstract of DOI:10.1021/jo00247a018

Cyclization and hydrolysis of aspartame were studied over a range of pH and temperatures by using an HPLC method which allows simultaneous analysis of the diastereomeric dipeptide and diketopiperazine products.The pH dependence of aspartic acid and phenylalanine racemization rates in the dipeptide-diketopiperazine system resulting from aspartame decomposition was determined.On the basis of these studies a general scheme of relative epimerization rates of amino acids in diketopiperazines and in the various positions and ionic states of peptides is presented.This scheme is discussed in terms of the carbanion mechanism of amino acid racemization and found to be consistent with it.Racemization rates in the diketopiperazine were greater than those of all ionic forms of the free amino acids and dipeptides except for fully protonated free amino acids and protonated terminal amino acids of peptides.In the neutral pH range the relative racemization rates in the DKP and dipeptides were DKP > amino terminal > carboxy terminal.Apparently contradictory results reported in the literature from dipeptide heating experiments were reanalyzed in terms of dipeptide-diketopiperazine-inverted dipeptide conversion.Viewed in this light, the literature is self-consistent and supports the generality of our scheme of relative racemization rates and mechanistic conclusions.