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 NH⋅⋅⋅OC 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.
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.
1,2,4,5-Tetrasubstituted-1H-imidazoles are a large family of heteroarene derivatives that are known to include natural products isolated from marine sponges and synthetic compounds possessing a broad range of biological and pharmacological properties. Consequently, a great deal of attention has been given to the synthesis of these heteroarenes and reviews covering some synthetic aspects of this topic have been published in recent years. However, none of these reviews provides a comprehensive overview of the several catalytic methods developed in the literature for the preparation of this important class of heteroarenes. This article review with 469 references, 63% of them being related to the period 2010-2017, aims to provide an updated critical picture of the catalytic processes reported in the literature up to the end of 2017 for the synthesis of 1,2,4,5-tetrasubstituted-1H-imidazoles illustrating these protocols and their characteristic features such as scope, efficiency, versatility, and limitations. The review also summarizes the mechanisms of the catalytic processes proposed for many of the reported processes.
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