Effect of tertiary amine on the carbodiimide-mediated peptide synthesis

Int J Pept Protein Res. 1991 Apr;37(4):252-6. doi: 10.1111/j.1399-3011.1991.tb00737.x.

Abstract

The effect of tertiary amine (DIEA) on reaction rate and product purity of a carbodiimide/HOBt-mediated peptide synthesis was studied. It was found that very rapid activation can be achieved using carbodiimide/HOBt in non-polar solvents, such as DCM. Although the HOBt is poorly soluble in DCM, the activation proceeds within 2 min, probably forming the HOBt-ester. By such a preactivation followed by a coupling in the presence of DIEA the rate of coupling is comparable with other rapid methods using BOP or TBTU, and no racemization was found in a model coupling (less than 0.1%). For comparison, syntheses of neurotensin by means of different coupling reagents (BOP, TBTU, OPfp-esters) and the DIEA-catalyzed coupling after carbodiimide/HOBt-activation under comparable conditions have shown that these procedures are of the same value in view of coupling efficiency and product purity.

MeSH terms

  • Amines / chemistry*
  • Amino Acid Sequence
  • Carbodiimides*
  • Chemical Phenomena
  • Chemistry
  • Ethylamines
  • Methylene Chloride
  • Molecular Sequence Data
  • Neurotensin / chemical synthesis
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Solubility
  • Solvents
  • Triazoles

Substances

  • Amines
  • Carbodiimides
  • Ethylamines
  • Peptides
  • Solvents
  • Triazoles
  • Neurotensin
  • Methylene Chloride
  • N,N-diisopropylethylamine
  • 1-hydroxybenzotriazole