COMU is uronium-type coupling reagent based on OxymaPure. It showed several advantages over classical benzotriazole-based coupling reagents such as higher solubility, water-soluble byproduct, and monitoring the reaction by changing of color. Although COMU is well known to perform excellent in solution, but its hydrolytic stability in DMF limits its use in automatic peptide synthesizer. Herein, we evaluated the hydrolytic stability of COMU in γ-valerolactone (GVL), acetonitrile (ACN) and N-formylmorpholine (NFM) and compared its stability against DMF. The stability of COMU after 24 h was found to be 88 and 89% in GVL and ACN, respectively, when compared in DMF (14%). Further, the demanding Aib-ACP decapeptide and JR decapeptide were successfully synthesized using COMU dissolved in GVL or ACN while Fmoc amino acids were dissolved in DMF. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

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