Abstract

Synthesis of protected amino acid derivatives has long been established as one of the most useful methods for peptide coupling, with applications in studies involving receptor-binding affinities and in protein stereochemical studies to elucidate enzymatic mechanisms. Amino acid esters incorporating glycine, proline, phenylalanine and related methyl esters have often been synthesized due to their usefulness, and the lysine derivative named N_a - Benzyloxycarbonyl - N_e - tert-butyloxycarbonyl - L - lysin - (N - hydroxy-succinimidester) has also been used extensively as a coupling agent for the formation of peptide bonds and to facilitate the synthesis of endorphins and enzyme inhibitors. However, efficient syntheses have been rare, and therefore a novel, multi-step sequence involving the selective addition and subsequent removal of several common protecting groups has recently been completed. This novel method was facilitated via the use of a sterically hindered base and a Dean-Stark trap to decrease the time required for complete cyclization. Reaction progress was monitored using thin layer chromatography, and all products have been analytically characterized using nuclear magnetic resonance spectroscopy and infrared spectroscopy. Enantioselectivity has been maintained for both of the amino acids arginine and lysine.

Key words: Protecting groups, amino acids, peptides, lactams.