β Scribed by Peng Li; Jie Cheng Xu
No coin nor oath required. For personal study only.
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 oc-C-dialkyl amino acids. Its efficiency was evaluated by HPLC and 'H 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, 'H 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.
π SIMILAR VOLUMES
An efficient scalable synthesis of 2-halothiazolium-type peptide coupling reagents has been developed. The key step is the formation of the 2-bromothiazole scaffold through cyclization of a-thiocyanato ketones with hydrogen bromide. Using this method, the new coupling reagent 2-bromo-N-methylthiazol
BmP (bromo tris(dimethylamino) phosphonium hexafluorophosphate) is a particularly suitable reagent for coupling N-methylated amino acids. It is stable and gives very high yields in short reaction times. Dipeptides are obtained without appreciable epimerization.