An efficient approach for solid-phase synthesis of peptidomimetics based on 4-imidazolidinones

An efficient method for the incorporation of an imidazolidinone moiety into peptide sequences via an alkylidene bridge between two neighboring amide bonds is presented. A benzotriazole-mediated reaction of aldehydes with resin-bound peptides provides N-terminal 4-imidazolidinone-peptide derivatives. The generated five-membered ring, which will be expected to have similar properties to ‘pseudo-prolines’, can be acylated at the secondary amine to allow elongation of the peptide backbone. NMR studies of imidazolidinone-containing peptides show the existence of cis/trans isomerization, typical for proline-based peptides.