Non-symmetric disubstituted malonamides rAA-mGly-AA', obtained from Meldrum's acid, were considered as methylene active compounds and a Knoevenagel condensation methodology was developed involving piperidine and activated 4 A molecular sieves as catalysts. The reaction is efficient, broad in scope, and easy to perform and allows access to E/Z mixtures of short malonyl dehydro peptides (MDHPs) rAA-m Delta(2)AA''-AA', partially modified retro peptides characterized by an interesting combination of retro and dehydro modifications in the same structure.

Starting from commercially available N-protected L-α-amino acids, N,N'-protected gem-diaminic units were obtained by a two-step methodology. A Hofmann reaction performed using a primary alcohol as the solvent to trap the isocyanate intermediate represents the key step of the new synthetic procedure. Then, the methodology was applied to α-carbamoyl α'-carboxyl aziridines, also functionalized with L-α-amino esters and stable gem-diaminic units characterized by an aziridine ring and by a retro-peptide modification were obtained. The use of the latter units in the retro-peptide chemistry allows to obtain modified peptides containing an aziridine ring able to behave as an electrophilic site and as a biomimetic structural analog of proline.

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A Rh-catalyzed addition reaction on non symmetric dehydro alanine retro-peptides is the key step in the reported three-step strategy for the diastereoselective synthesis of differently functionalized benzyl malonyl peptides (74% overall yield)

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