On the Manner of Cyclization of N-Acylated Aspartic and Glutamic Acid Derivatives

Abstract

When synthesizing arylpiperazine library modified with N-acylated amino acid derivatives (e.g., cyclized aspartic acid, cyclized glutamic acid, proline) we wished to rapidly determine the way of cyclization of N-acylated glutamic acid derivatives. During concomitant cleavage and cyclization two alternative routes were possible—either formation of six-member imide (glutarimide) or five-member lactam. Application of MS/MS and 1H NMR method allowed us to establish that cyclization of N-acylated glutamic acid derivatives preceded to lactams—N-acylated pyroglutamic acid derivatives. Under acidic treatment the Lantern bound N-acylated glutamic acid derivatives underwent concomitant cleavage and cyclization. Herein, we studied two alternative cyclization routes—imides, lactams. It was found that cyclization of N-acylated glutamic acid derivatives yielded pyroglutamic acid derivatives (Structure C).