New MraYAA Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole.

New inhibitors of the bacterial transferase MraY from Aquifex aeolicus (MraYAA), based on the aminoribosyl uridine central core of known natural MraY inhibitors, have been designed to generate interaction of their oxadiazole linker with the key amino acids (H324 or H325) of the enzyme active site, as observed for the highly potent inhibitors carbacaprazamycin, muraymycin D2 and tunicamycin. A panel of ten compounds was synthetized notably thanks to a robust microwave-activated one-step sequence for the synthesis of the oxadiazole ring that involved the O-acylation of an amidoxime and subsequent cyclization. The synthetized compounds, with various hydrophobic substituents on the oxadiazole ring, were tested against the MraYAA transferase activity. Although with poor antibacterial activity, nine out of the ten compounds revealed the inhibition of the MraYAA activity in the range of 0.8 µM to 27.5 µM.

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5'-alkynylation.

The 5'-alkynylation of uridine-derived aldehydes is described. The addition of alkynyl Grignard reagents on the carbonyl group is significantly influenced by the 2',3'-di-O-protecting groups (R1): O-alkyl groups led to modest diastereoselectivities (65:35) in favor of the 5'R-isomer, whereas O-silyl groups promoted higher diastereoselectivities (up to 99:1) in favor of the 5'S-isomer. A study related to this protecting group effect on the diastereoselectivity is reported.

Synthesis and Characterization of Polystyrene-Supported Piperazine-Substituted Triazoles by CuAAC and First Evaluation for Metal Ion Extraction.

The goal of this work was to synthesize substituted polystyrene for metal extraction and/or depollution by introduction of substituted piperazines as chelatants starting from Merrifield polymer. After transformation of Merrifield's resin in azidomethyl polystyrene, click-chemistry using copper (I)-catalyzed Huisgen's reaction (CuAAC) was performed to prepare different polymers grafted with 1,4-triazoles bearing the piperazines, containing an alkyne as the other counterpart in the CuAAC. The polymers were then first tested for their efficiency to remove various metal ions from neutral aqueous solutions (Fe3+, Ni2+, Cu2+, Zn2+ and Pb2+). The polymers were found to extract Ni2+ and Zn2+ with low efficiencies ≤40%. For Fe3+ and Cu2+, the average extraction was around 80%, and for Pb2+ around 50%. The global selectivity for these polymers was found to be in the order of Fe3+ ≥ Cu2+ > Pb2+ >> Ni2+ > Zn2+.

3-[(4-Phen-oxy-phen-yl)sulfan-yl]-5-phenyl-1H-1,2,4-triazole.

The title compound, C20H15N3OS, is V-shaped. In the 4-phen-oxy-phenyl group, the two rings are inclined to one another by 74.52 (13)°. These rings are inclined to the triazole ring by 72.20 (15) and 72.30 (15)°, respectively. The phenyl ring is inclined to the triazole ring by 10.85 (12)°. In the crystal, mol-ecules are linked via N-H⋯N hydrogen bonds, forming chains propagating along [010]. These chains are linked via pairs of C-H⋯S hydrogen bonds, forming sheets lying parallel to the ac plane.