No abstract

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.

Gramicidin S (GS), one of the oldest commercially used peptide antibiotics, is known for its robust antibacterial activity against both Gram-positive and Gram-negative bacterial strains. Although it was discovered well over 70 years ago, its clinical potential was limited to topical applications because of its high hemolytic activity. To overcome this side effect, significant efforts have been invested in the chase for GS analogues with high therapeutic index (e.g., high antimicrobial activity and low hemolytic activity) in the past decades. In this Perspective, the structural properties and biological profiles (including the recently discovered activities) of representative GS analogues designed by different approaches are described and analyzed. We also present how the general structure–activity relationships were established and how they could help in the design of more efficient GS analogues.

Abstract:The C2-symmetric electron-poor ligand (R)-BINOP-F (4) was prepared by reaction of (R) Moreover, a second exchange process renders the diastereotopic BINOP-F phosphorus atoms equivalent. These processes were studied by the application of variable-temperature 1 H, 31 P, and 17 O NMR spectroscopy, variable-pressure 31 P and 17 O NMR spectroscopy, and, using a simpler model complex, density functional theory (DFT) calculations. The results point to a dissociative mechanism of the aquo ligand and a pendular motion of the BINOP-F ligand. NMR experiments show an energy barrier of 50.7 kJ mol -1 (12.2 kcal mol -1 ) for the inversion of the pseudo-chirality at the ruthenium center.-

Cationic arene and cyclopentadienyl complexes of iron and ruthenium incorporating chiral bidentate ligands have been shown to be efficient Lewis acid catalysts for the asymmetric Diels ± Alder reaction between enals and dienes. [1±5] Our research in this area has focused on cyclopentadienyliron and -ruthenium complexes, the former giving higher rates and enantiomeric excesses and the latter being more stable and easily recycled. [2] Enantioselectivity in the Ru complexes was strongly increased on changing the aryl groups in the ligand backbone, that is by using 3 rather than 2 as precatalysts. [2a] The structurally characterized complex [CpRu(biphop-F)-(methacrolein)][SbF 6 ] (1 d; biphop-F 1,2-bis[bis(pentafluoro-phenyl)phosphanyloxy]-1,2-diphenylethane)has provided a detailed picture of the catalyst/substrate interaction and of the influence of the anion on the rate of catalysis. [2b] Evidence from the solid-state structure of 1 d and from F/H NMR correlation spectra in solutions of the BF 4 À and the PF 6 À analogues (1 b and 1 c, respectively) point to ion pairs in which the anion interacts with both the bound substrate and the cationic catalyst. [2a, b] We concluded that the anion slows down product/substrate exchange at the catalyst site. Consequently, complex 1 e, which incorporates the tetrakis[3,5bis(trifluoromethyl)phenyl] borate anion (TFPB) whose bulk renders this proximity impossible, showed the highest activity.Another way to bring about a larger separation of the anion from the enal group in the catalyst site is to increase the size of the catalyst×s capping ligand, for example by changing from the cyclopentadienyl to the indenyl complexes. With an indenyl ligand the question of preferred rotamers arises. Moreover, the propensity of the indenyl ligand to undergo a slip/fold rearrangement [6] risks the occurrence of a different mode of enal binding and reactivity than the desired single coordination site Lewis acid. The results described herein provide answers to these questions. The properties of the indenyl complexes are indeed significantly altered from those of the cyclopentadienyl analogues, and diastereoselectivities not previously encountered in the Diels ± Alder reaction of enals with dienes are realized. We also note that despite the detailed attention that indenyl complexes of Group 8 metals have received, asymmetric catalytic reactions with this family of compounds have not been reported. [7] Given that the reaction of [Ru 3 (CO) 12 ] with indene affords a low yield of the resultant complex, [8] we opted for the thermal substitution of the two PPh 3 ligands in [IndRu-(PPh 3 ) 2 Cl] [9] (7) by the bidentate biphop-F [2c, 10] (8) and Me 4 biphop-F (9) [2a] ligands to give the Ru complexes 10 and 11 respectively (Scheme 1).This reaction was complete in 1.5 h, whereas with the cyclopentadienyl analogue the reaction with the very similar ligand 1,2-bis[bis(pentafluorophenyl)phosphanyloxy]cyclopentane (cyclop-F) [2d] took one week to complete. In analogy to the mechanism established...

A new methodology for the asymmetric synthesis of quaternary alpha-substituted amino acids using memory of chirality has been developed. The strategy utilizes the dynamic axial chirality of tertiary aromatic amides to memorize the initial chirality of an alpha-amino acid during an enolization step. Starting from five different l-amino acids, the corresponding oxazolidin-5-ones containing a tertiary aromatic amide group have been synthesized in one step and then alkylated with various electrophiles, with good yields and enantioselectivities (up to 96% and up to >99% after recrystallization). One-step deprotection affords enantioenriched or enantiopure quaternary alpha-amino acids. We describe here the optimization process, the results obtained in each series and a plausible explanation, based on NMR studies, DFT calculations and crystallographic structures. The methodology presented herein constitutes an efficient synthesis of enantiopure quaternary alpha-amino acids (three steps only) starting from tertiary l-amino acids, without any external source of chirality.

static sp 3 chirality static sp 3 chirality dynamic sp 2 chirality Y A B or chiral pool at the reacting center

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.