Lactam ring stability of stereoisomers of 4-amino-substituted pyroglutamic acids in acidic medium

The acid hydrolysis of the lactam ring of cis and trans stereoisomers of 4-(1-piperidyl)-, 4-dibenzylamino-, 4-[(methyl)(phenyl)amino]-, 4-phenylamino-, and 4-(4-methoxyphenyl)-aminopyroglutamic acids was studied. It was shown that the relative stability of the lactam ring of 4-amino-substituted pyroglutamic acids to acid hydrolysis depends both on the structure of a substituent in the position 4 and on the configuration of the compounds studied. Among these compounds, 4-amino-1-arylpyroglutamic acids were the most stable in acidic medium. The trans isomers are more stable than the corresponding cis isomers.