Synthesis and study of (2S,4S)-4-arylamino-2-carboxy-5-pyrrolidones

Structure and Properties of 4‐Amino Derivatives of 5‐Oxoproline

“…Lactams of type A, which result from the participation of the α-amino and γ-COOH groups are not formed, as it was considered earlier. [6,10] Isomeric lactams, that is, 4-arylamino-5-oxoprolines 16 and 17, were easily converted in acidic medium into more stable compounds 6 and 7.…”

“…Earlier, we assigned a structure of type A to these formed lactams; [6] this assignment did not contradict the available data regarding the properties of these compounds. However, the results obtained recently, in particular on the syn- thesis of 4-arylaminoglutamate derivatives with a tertiary amino group, [8b] made it necessary to critically examine that data.…”

“…Acidic hydrolysis of dimethyl (2S,4S)-4-arylamino-Nphthaloylglutamates obtained from (2S,4RS)-4-bromoglutamate derivative 1 (Scheme 1) resulted in lactams (4-substituted 5-oxoprolines) as the only reaction products. [6] When the substituent is a fragment of a primary amine, in particular arylamine, both γ-and α-carboxylic groups can participate in the lactam-formation process to give A and B pyroglutamic acids, respectively (Scheme 1).…”

“…Glutamic acid in aqueous solutions with pH values close to neutral is converted into pyroglutamic acid. [3] The derivatives of glutamic acid with 4-substituents, such as amino, [4] phenyl, [5] arylamino, [6] thiopyridinyl [7] and others, [8] are able to form lactams in acidic and neutral media. It should be noted that the amount of lactam formed increases when the glutamic acid contains aromatic and heterocyclic substituents.…”