δ-Valerolactamic Quaternary Amino Acid Derivatives: Enantiodivergent Synthesis and Evidence for Stereodifferentiated ß-Turn-Inducing Properties.

Enantiopure (R) and (S) cyclic α,α-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The (R)-configured δ-valerolactam 11 was converted into diastereoisomeric pseudopeptides to investigate its ability to induce secondary structures in peptidomimetics. Conformational studies of these pseudopeptides were carried out in the solid state (X-ray diffraction), in solution (NMR analyses), and in silico (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce ß-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of α,α-disubstituted amino acid into a representative pseudopeptidic sequence by N- then C-elongation and N-debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetics.

Threats to large brown algal forests in temperate seas: the overlooked role of native herbivorous fish.

Canopy-forming algae are declining globally due to multiple disturbances. This decline has recently been on the increase due to the spread of some tropical herbivorous fishes. This new phenomenon has drawn attention to the effects of fish herbivory in temperate areas, which have been assumed to be negligible compared to that of invertebrates, such as sea urchins. In this study, the impact of a Mediterranean native herbivorous fish (Sarpa salpa, salema) was assessed on the canopy-forming seaweed Cystoseira amentacea var. stricta. Cystoseira amentacea forms belts in the infralittoral fringe of wave-exposed shores, which has so far been considered a refuge from fish herbivory. To test the effects of salema feeding on natural C. amentacea belts, an innovative herbivore deterrent device was conceived. Salema had a significant effect on C. amentacea by decreasing algal size, biomass and fertility, by up to 97%. The results suggest that the contribution of salema feeding to the loss of Cystoseira forests in the Mediterranean may have been overlooked. In addition, the analysis of temporal and spatial patterns of salema landings in the Mediterranean Sea suggests that salema abundance may have increased recently. Thus, along with invertebrate herbivory and anthropogenic stressors, fish herbivory may also represent a potential threat to algal forests in temperate areas.

Asymmetric synthesis of α,α-disubstituted amino acids by cycloaddition of (E)-ketonitrones with vinyl ethers.

Original acyclic (E)-α,α-dialkylketonitrones bearing a chiral auxiliary on their nitrogen atom were synthesized and successfully employed for the asymmetric synthesis of α,α-disubstituted amino acids using regio- and stereocontrolled 1,3-dipolar cycloaddition reactions with vinyl ethers. N-Glycosyl chiral auxiliaries were found to provide excellent exo- and π-facial stereocontrol. The obtained enantiopure cycloadducts were selectively transformed into functional α,α-disubstituted amino acids and related ß-peptides through the highly regioselective opening of an intermediate quaternary anhydride.

Enantioselective ruthenium-catalyzed 1,3-dipolar cycloadditions between C-carboalkoxy ketonitrones and methacrolein: solvent effect on reaction selectivity and its rational.

A catalytic 1,3-dipolar cycloaddition between carboalkoxy ketonitrones and methacrolein under the effect of chiral ruthenium Lewis acid (R,R-1) was developed with high regio-, diastereo-, and enantiocontrol. The diastereochemical outcome of the cycloaddition reaction is marked by a significant solvent effect, and a divergent endo or exo control can be tuned by an appropriate choice of both the solvent and the N- and O-substituents of the ketonitrone. A rationale of the solvent effect, based on the computational study of the interactions between the methacrolein-Ru complex and its counteranion (SbF6(-)), is proposed to explain the selectivities obtained.

Access to alpha-substituted amino acid derivatives via 1,3-dipolar cycloaddition of alpha-amino ester derived nitrones.

Amino acid derived nitrones were conveniently synthesized in good-to-excellent yields by condensation of alpha-ketoesters with N-benzylhydroxylamine. The cycloaddition reactions of these nitrones with different alkenes were investigated under thermal solvent-free conditions. Considering conversions, yields, and selectivities, alkyl vinyl ethers have proven to be valuable partners to achieve this transformation, which creates a tetrafunctionalized stereogenic quaternary center. From the adducts derived from vinyl ethers, a three-step access to highly functionalized alpha-substituted amino acid derivatives is described.

Regioselective Baeyer-Villiger oxidation in 4-carbonyl-2-azetidinone series: a revisited route toward carbapenem precursor.

A novel synthesis of acetoxyazetidinone 2 is presented. The azetidinone ring of compounds 7 is formed by C-3/C-4 cyclization of (2R,3R)-epoxybutyramide precursors 6, N-protected with a benzhydryl group. N-Deprotection by photoactivated bromination and acidic treatment leads to compounds 10 with various CO-R substituents at C-4. Transformation of these substituents by Baeyer-Villiger oxidation gives the desired regioisomer 11 with the cyclopropyl side-group which is the only group (among R = H, Ph, t-Bu, i-Pr, c-Pr) able to satisfy both the steric requirements of the cyclization step and the electronic requirements of the oxidative rearrangement step.