Marc Lecouvey

Xanthyletin (1), edulinin (2), 1-methyl-2-[(E)-(prop-1-enyl)]quinolin-4-one (3), 1,2-dimethylquinolin-4-one (4), lonchocarpol A (5), grandisinin (6), citracridone-I (7) and 5-hydroxynoracronycin (8) were isolated from alkaloid extracts of the root bark of Citrus aurantifolia. Their structures were characterized using spectral data (NMR, HRMS, and IR). Furthermore, compounds 2, 3, 4, and 6 known in the literature have been isolated for the first time in Citrus aurantifolia. However, compounds 1, 5, 7 and 8 are already known from the plant studied. The concentration required to reduce 50% of free radicals (RC50) was carried out. Compounds 3 (RC50= 185.836 µmol/L) and 4 (RC50= 218.277 µmol/L) compared with vitamin C (RC50= 17.033 µmol/L) showed antioxidant efficacy. The highest anticholinesterase activity was observed for compound 6 at 21.129 µM followed by compounds 3 and 4 at 251.130, 287.208 µM, respectively.

Among phosphorylated derivatives, phosphinates occupy a prominent place due to their ability to be bioisosteres of phosphates and carboxylates. These properties imply the necessity to develop efficient methodologies leading to phosphinate scaffolds. In recent years, our team has explored the nucleophilic potential of silylated phosphonite towards various electrophiles. In this paper, we propose to extend our study to other electrophiles. We describe here the implementation of a cascade reaction between (trimethylsilyl)imidates and hypophosphorous acid mediated by a Lewis acid allowing the synthesis of aminomethylenebisphosphinate derivatives. The present study focuses on methodological development including a careful NMR monitoring of the cascade reaction. The optimized conditions were successfully applied to various aliphatic and aromatic substituted (trimethylsilyl)imidates, leading to the corresponding AMBPi in moderate to good yields.

Among phosphorylated derivatives, phosphinates occupy a prominent place due to their ability to be bioisosteres of phosphates and carboxylates. These properties imply the necessity to develop efficient methodologies leading to phosphinate scaffolds. For the past years our team have explored the nucleophilic potential of silylated phosphonite towards various electrophiles. In this paper, we propose to extend our study over other electrophiles. We describe here the implementation of a cascade reaction between (trimethylsilyl)imidates and hypophosphorous acid mediated by a Lewis acid allowing the synthesis of aminomethylenebisphosphinate derivatives.

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and the hydroxyl radical (center dot OH) have specific functions in biological processes, while their uncontrolled production and reactivity are known to be determining factors in pathophysiology. Methionine (Met) residues act as endogenous antioxidants, when they are oxidized into methionine sulfoxide (MetSO), thus depleting ROS and protecting the protein. We employed tandem mass spectrometry combined with IR multiple photon dissociation spectroscopy to study the oxidation induced by OH radicals produced by gamma radiolysis on model cyclic dipeptides c(LMetLMet), c(LMetDMet), and c(GlyMet). Our aim was to characterize the geometries of the oxidized peptides in the gas phase and to understand the relationship between the structure of the 2-center 3-electron (2c-3e) free radical formed in the first step of the oxidation process and the final compound. Density functional theory calculations were performed to characterize the lowest energy structures of the final product of oxidation and to interpret the IR spectra. Collision-induced dissociation tandem mass spectrometry (CID-MS2) experiments of oxidized c(LMetLMet)H+ and c(LMetDMet)H+ led to the loss of one or two oxidized sulfenic acid molecules, indicating that the addition of one or two oxygen atoms occurs on the sulfur atom of both methionine side chains and no sulfone formation was observed. The CID-MS2 fragmentation mass spectrum of oxidized c(GlyMet)H+ showed only the loss of one oxidized sulfenic acid molecule. Thus, the final products of oxidation are the same regardless of the structure of the precursor sulfur-centered free radical.

Single crystals of B-DNA and Z-DNA oligomers were analyzed under high hydrostatic pressure and their behavior was compared to the A-DNA crystals already known. The amplitude of the base compression, when compared to the A-form of DNA (0.13 Å/GPa), was higher for the Z-DNA (0.32 Å/GPa) and was the highest for the B-DNA (0.42 Å/GPa). The B-DNA crystal degraded rapidly around 400–500 MPa, while the Z-structure was more resistant, up to 1.2 GPa.