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Updated: Oct 23, 2026

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library
Published on: June 20, 2014
Effect of tertiary amine on the carbodiimide-mediated peptide synthesis
M Beyermann1, P Henklein, A Klose
1Institute of Drug Research, Academy of Sciences of the G.D.R.
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.
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