Prevention of diketopiperazine formation in peptide synthesis by a simultaneous deprotection–coupling procedure: entrapment of reactive nucleophilic species by in situ acylation

Abstract

Hydrogenolysis of Z-amino acid-D-Pro-OMe dipeptides in the presence of acetic acid results, almost quantitavely, in the formation of diketopiperazines, whereas in the presence of Boc- or 2-(trimethylsilyl)ethoxycarbonyl protected amino acid pentafluorophenyl or N-hydroxysuccinimidyl active esters, protected tripeptides are formed; a simultaneous deprotection/acylation methodology with potential utility for peptide synthesis thus results.