Understanding the structure/reactivity of aminium/uronium salts as coupling reagents in peptide synthesis

Abstract

Coupling reagents based on onium (aminium/uronium) salts based on HOBt and HOAt are more frequently used in solid-phase peptide synthesis than the classical carbodiimide methods. The structure of the carbon skeleton has a determining role in the efficiency of the reagent for the activation step. Simple theoretical calculations using the AM1 semiempirical Hamiltonian as implemented in the MOPAC program provide a rational way to correlate the reactivity of different aminium/uronium salts with the structure of the carbon skeleton.