Automated solid-phase peptide synthesis: Use of 2-(1H-benzotriazol-1-yl)-1,1,3,3,-tetramethyluronium tetrafluoroborate for coupling of ert- butyloxycarbonyl amino acids

Abstract

2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) has been adapted for use as a coupling reagent for tert-butyloxycarbonyl (Boc) amino acids in automated solid-phase peptide synthesis. When compared to the existing preformed symmetrical anhydride procedure employing dicyclohexyl-carbodiimide (DCC), the use of TBTU in the presence of 1-hydroxybenzotriazol (HOBt) provides a more efficient coupling procedure for Boc-amino acid derivatives. Overall cycle times using TBTU HOBt coupling reagents (30 min) compare favorably to those of the DCC-mediated procedure (approx 65 min). Dimethyl-formamide can be used as the sole solvent for both activation and coupling reactions. ..