Over the past 20 years, the field of foldamers has rapidly increased. Many β-peptides have already been described and shown interesting properties. γ-Peptides have more recently emerged but seem to be very interesting as well. In this review, we will cover every peptidomimetic oligomer that contains a γ-amino acid or an analogue and presents a structural feature. It includes γ-peptides but also hybrid α-γ peptides, β-γ peptides and analogues such as oligoureas or aminoxy acids. We will present the biological properties of these oligomers.

A general strategy for the amino acid homologation via Blaise reaction and subsequent reduction is presented. This strategy involves the preparation of protected alpha-amino nitriles from the corresponding amino acids, followed by the zinc-mediated condensation of tert-butyl bromoacetate, to give the imidazolidones after iminozincate cyclization. Reduction gave the saturated imidazolidinones with cis or trans stereochemistry, depending on the reduction conditions. This strategy was applied to nonfunctionalized amino acids and to functionalized amino acids such as serine and aspartic acid. Additionally, acidic hydrolysis of cis or trans imidazolidinones to the corresponding chiral 4-aminopyrrolidones is described.

Original αγα tripeptides containing one β,γ-diamino acid have been synthesized and their conformation determined by extensive NMR and molecular dynamic studies. These studies revealed the presence of a C(9) hydrogen bonded turn around the β,γ-diamino acid which was stabilized by bulky side chains of the preceding residue. This turn can be considered as a mimic of the well-known γ-turn.

Small α/γ-peptides alternating α-aminoisobutyric acid and cyclic γ-amino acid residues are described. NMR studies together with restrained simulated annealing revealed that an extended backbone conformation largely dominates in solution for as short as 4-residues long oligomers. This new fold type is devoid of any hydrogen bond and characterized by a four-fold symmetry.

We describe here an efficient synthesis of both diastereomers of cyclic β,γ‐diamino acids starting from l‐glutamic acid, based on the Blaise reaction. We show that by changing the protecting group, we can access either the five‐membered‐ring lactam, which can be used as a β‐amino acid, or the six‐membered‐ring lactam, as a γ‐amino acid. We also discovered an interesting kinetic resolution during the synthesis that allowed easier separation of diastereomers. The products can be easily used in peptide synthesis, and a tetramer with alternating trans cyclic γ‐amino acid and AIB (2‐aminoisobutyric acid) residues was synthesized.

The synthesis of orthogonally protected diastereo- and enantiopure β,γ-diamino acids starting from natural α-amino acids is described, as well as its application to the synthesis of fully protected 3-deoxyaminostatine.

Imidazole derivatives R 0190Amino Acid Homologation by the Blaise Reaction: A New Entry into Nitrogen Heterocycles. -Treatment of Cbz-protected amino nitriles of type (IV) derived from α-amino acids with bromoacetate and subsequent base-mediated cyclization provides a new approach to imidazolidinones like (VI). These compounds smoothly undergo stereoselective reduction to give cis-and/or trans-substituted imidazolidinones. Hydrolysis of the latter does not yield the expected β,γ-diamino acids but cyclization products like (IX) and (X). Blaise reaction of the functionalized amino nitrile (XIII) provides the lactam (XIV) instead of the corresponding imidazolidinone. (XIV) undergoes stereoselective reduction giving the trans-substituted lactam (XV). -(HOANG, C. T.; BOUILLERE, F.; JOHANNESEN, S.; ZULAUF, A.; PANEL, C.; POUILHES, A.; GORI, D.; ALEZRA*, V.; KOUKLOVSKY, C.; J.

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