A novel thiazolium type peptide coupling reagent for hindered amino acids

Article abstract of DOI:10.1016/S0040-4039(99)01763-3

A highly efficient coupling reagent, 2-bromo-3-ethyl-4-methyl thiazolium tetrafluoroborate (BEMT), was designed, synthesized and successfully applied to the synthesis of oligopeptides containing N-alkyl or α-C-dialkyl amino acids. Its efficiency was evaluated by HPLC and ¹H NMR methods, and demonstrated by synthesis of a number of N-methyl-rich peptide segments with good yields and negligible racemization. The mechanism of coupling was studied by HPLC, ¹H NMR and IR monitoring; it is proposed that labile (acyloxy)thiazolium salts and N-protected amino acid bromides were the major active intermediates with concomitant formation of N-ethyl-4-methyl thiazolidones and a small amount of oxazolones and N-protected amino acid anhydrides.