COMU: a third generation of uronium-type coupling reagents.

COMU is a third generation of uronium-type coupling reagent based on ethyl 2-cyano-2-(hydroxyimino)acetate (Oxyma) as well as a morpholino carbon skeleton. The presence of the morpholino group has a marked influence on the solubility, stability and reactivity of the reagent. COMU performed extremely well in the presence of only 1 equiv. of base, thereby confirming the effect of the hydrogen bond acceptor in the reaction. The by-products of COMU are water soluble and easily removed, making it an excellent choice of coupling reagent for solution-phase peptide synthesis. Finally, COMU shows a less hazardous safety profile than benzotriazole-based reagents, such as HATU and HBTU, which in addition exhibit unpredictable autocatalytic decompositions and therefore a higher risk of explosion. Furthermore, in contrast to benzotriazole-based reagents, COMU is significantly less likely to cause allergic reaction.