Facile synthesis and cleavage of imidazolidines in a novel protection strategy for the preparation of peptides containing a reduced amide bioisostere

Unsymmetrical imidazolidines were obtained in 75-91% yield by treating monoalkoxycarbonyl vicinal diamines at room temperature with aqueous 37% formaldehyde in the presence of Montmorillonite KSF as a solid catalyst. The imidazolidines were shown to be useful intermediates in a novel protection strategy for the synthesis of peptide analogues containing a reduced glycine amide bioisostere. The imidazolidine intermediate was cleaved conveniently and efficiently by 50% TFA in methylene chloride.