Kinetic studies on enamine catalysis provided insight into the rate determining step(s) of peptide catalyzed conjugate addition reactions between aldehydes and nitroolefins. They demonstrate that not enamine formation but both the reaction of the enamine with the electrophile and hydrolysis of the resulting imine are rate limiting. These results allowed for reducing the catalyst loading by a factor of 10 to as little as 0.1 mol %. This is the lowest catalyst loading that has been achieved so far in enamine catalysis with low molecular weight catalysts for a broad range of substrates.

The synthesis of all-cis amide (NtBu)-glycine oligomers up to 15 residues long by a blockwise coupling approach is reported. The structure and dynamical behavior of these peptoids have been studied by X-ray crystallography, NMR and molecular modeling. Analyses reveal that the folding of these oligomers is driven by weak CH···O=C hydrogen bonding along the peptoid backbone and London interaction between tBu···tBu side-chains.

One is enough: The dipeptide Boc‐L‐Phe‐D‐Oxd‐OBn (Boc=tert‐butoxycarbonyl, Phe=phenylalanine, Oxd=4‐methyl‐5‐carboxy oxazolidin‐2‐one, Bn=benzyl; see picture; gray C, white H, red O, blue N) spontaneously forms uniform fibers consisting of parallel infinite linear chains arising from single intermolecular NH⋅⋅⋅OC hydrogen bonds. This is the absolute borderline case of a parallel β‐sheet structure.

A series of oligomers of the type Boc-(L-Phe-D-Oxd)(n)-OBn (Boc = tert-butoxycarbonyl; Oxd = 4-methyl-5-carboxy oxazolidin-2-one; Bn = benzyl) were prepared for n = 2-5. The shortest oligomer, Boc-(L-Phe-D-Oxd)(2)-OBn, aggregates and forms a fiber-like material with an anti-parallel beta-sheet structure in which the oligopeptide units are connected to each other by only one intermolecular hydrogen bond. The longer oligomers exhibit structural heterogeneity. They start to organize into secondary structures by the formation of intramolecular hydrogen bonds at the pentamer level. Microscopy and diffraction of the oligomers indicated a crystalline character for only the shorter ones.

Some compounds containing the L‐Phe‐D‐Oxd [L‐Phe = L‐phenylalanine; D‐Oxd = (4R,5S)‐4‐carboxy‐5‐methyl oxazolidin‐2‐one] moiety have been prepared and their properties as supramolecular material have been determined. Some derivatives of the dipeptide L‐Phe‐L‐Phe (which usually forms nanotubes) and some long‐chain derivatives that behave as low‐molecular‐weight gelators have been prepared. We have also replaced the D‐Oxd moiety with a D‐Pro (D‐Pro = D‐proline) moiety to check if the presence of the Oxd moiety was essential for the existence of those materials. In contrast to the D‐Oxd‐containing compounds, no material was ever formed with any of the D‐Pro‐containing molecules. This outcome suggests that the L‐Phe‐D‐Oxd moiety may be defined as a “privileged scaffold” for the formation of supramolecular materials and it can be introduced into more complex structures to induce some selected properties in the solid state.

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A small library of stereoisomeric pseudopeptides able to make gels in different solvents has been prepared and their attitude to make gels in the presence of several metal ions was evaluated. Four benzyl esters and four carboxylic acids, all containing a moiety of azelaic acid (a long chain dicarboxylic acid) coupled with four different pseudopeptide moieties sharing the same skeleton (a phenyl group one atom apart from the oxazolidin-2-one carboxylic group), were synthesized in solution, by standard coupling reaction. The tendency of these pseudopeptides to form gels was evaluated using the inversion test of 10 mM solutions of pure compounds and of stoichiometric mixtures of pseudopeptides and metal ions. To obtain additional information on the molecular association, the gel samples were left dry in the air to form xerogels that were further analyzed using SEM and XRD. The formation of gel containing Zn(II) or Cu(II) ions gave good results in term of incorporation of the metal ions, while the presence of Cu(I), Al(III) and Mg(II) gave less satisfactory results. This outcome is a first insight in the formation of stable LMWGs formed by stoichiometric mixtures of pseudopeptides and metal ions. Further studies will be carried out to develop similar compounds of pharmacological interest.

Foldamers are artificial molecules capable of organization into well defined secondary structures such as helixes, β sheets and turns. The essential requirement for an oligomer to qualify for inclusion in the foldamer family is to possess a well defined, repetitive secondary structure, imparted by conformational restrictions imposed by the monomeric unit. These compounds may be composed of subunits of any kind, but most of them contain unusual amino acids and/or aromatic units. We describe the synthesis, the conformation analysis and the physical properties (in the solid state) of pseudopeptide foldamers containing imido‐type functions, obtained by coupling the nitrogen of a 4‐carboxy oxazolidin‐2‐one unit with the carboxylic acid moiety of the next unit, which may be another 4‐carboxy oxazolidin‐2‐one or an amino acid. Such an imido‐type function is characterized by a nitrogen atom connected both to an endocyclic and to an exocyclic carbonyl group, and tends always to adopt the trans conformation. As a consequence of this remarkable property, which causes local constraint, these imido‐type oligomers are forced to fold in ordered conformations. In combination with interactions of other kinds (H bond, apolar interactions, etc.), these lead to the formation of supramolecular materials. The synthetic approach is highly tuneable with endless variations, so materials with required properties may be prepared “on demand”, simply by changing the design and the synthesis.