Parham-type cycliacylation with Weinreb amides. Application to the synthesis of fused indolizinone systems

[reaction: see text] Weinreb amides behave as efficient internal electrophiles in Parham-type cycliacylation reactions. Thus, aryl- and heteroaryllithiums generated by lithium-halogen exchange undergo intramolecular cyclization to give fused indolizinone systems as pyrrolo[1,2-b]isoquinolines, thieno[2,3-f]indolizinones, and pyrrolo[1,2-b]acridinones in high yields.     

Langmuir monolayer characteristics of a perfluoroaryl surfactant: 10-Perfluorobenzyl-decan-1-ol (PBD)

A surfactant containing the perfluorobenzyl moiety attached at the 10 position of decanol (10-perfluorobenzyldecan-1-ol, PBD) was synthesized and employed for Langmuir monolayer characterization, using surface pressure (π) and electric surface potential (ΔV)-mean molecular area (A) isotherms. Both static and dynamic stability experiments demonstrate that the monolayers formed by PBD are of satisfactory stability. Characteristic dendritic structures were observed with Brewster Angle Microscope (BAM) upon the whole compression up to the vicinity of collapse, where 3D crystallites appeared. The monolayer thickness is found to be comparable to the PBD molecule length. It occurs that ΔV has negative value even at large molecular areas, and decreases gradually along the compression, reaching a minimum of ca. −500 mV. Using the Helmholtz model, the apparent dipole moment was calculated upon film compression. The measurements were complemented with semi-empirical calculations involving molecular geometry optimization and dipole moment estimation.     

DFT study of the EPR spectral pattern of propagating methacrylic radicals

The EPR spectral pattern observed in the bulk polymerization of methacrylic monomers was theoretically investigated by DFT methodology. The conformational analysis of the propagating radical by the rotation around the C–C_β bond, was performed using the B3LYP/6-31G^* computational scheme. To obtain accurate values of the isotropic hyperfine coupling constants (hfccs) a higher level protocol, B3LYP/TZVP//B3LYP/6-31G^*, was applied. The experimental 13-line spectrum registered at the first stage of the polymerization was assumed to correspond to a free rotating radical in a fluid medium and it was simulated just considering the most stable conformation. The 9-line spectrum registered at high conversions was interpreted in terms of highly hindered rotational conformers frozen in the very viscous medium. This spectrum was well reproduced by a model which considers the sum of the individual spectra of the conformations spread around the most probable. Each of these contributing spectra was obtained on the basis of the computed hfccs for the considered conformations and weighted by his relative Boltzmann population according to the DFT analysis. Besides, the calculated hfccs showed an excellent agreement with those predicted by the Heller–McConnell relationship, which confirms the coherence of the DFT methodology for this kind of calculations.     

Isolation of a stable 1-iridabicyclo[3.2.0]hepta-1,3,6-triene and its reversible transformation into an iridacycloheptatriene

Reaction of the iridacyclopentadiene complex 2 with 2-butyne yields a mixture in equilibrium of the iridacycloheptatriene 3 and a novel 1-iridabicyclo[3.2.0]hepta-1,3,6-triene, 4.     

Pyridazines. Part 31: synthesis and antiplatelet activity of 4,5-disubstituted-6-phenyl-3(2H)-pyridazinones

This paper describes the synthesis and the antiplatelet activity of a series of 4,5-disubstituted-6-phenyl-3(2H)-pyridazinones. Some of these compounds show a dose-dependent activity and were found to be more active than their 5-substituted analogues.     

Intercalation Compounds between Ethyl 2-oxocyclopentanecarboxylate and Saponite

The retention of ethyl 2-oxocyclopentanecarboxylate by a saponite has been studied. Intercalation compounds were prepared by two different methods: 1) in repose at room temperature and 2) heating at 60 °C under reflux. Contact times between 2 and 12 days were considered for each method. The intercalation compounds obtained were characterized by X-ray diffraction, infrared spectroscopy, chemical analyses and thermal analyses. This characterization indicates that the organic compound is retained both in the interlayer region and at the edge of the clay particles. The amount retained outside of the interlayer space is eliminated by careful washing with benzene and cyclohexane. The results obtained when using acid-activated saponite -obtained by treatment of the clay with dilute HCl solutions- in the intercalation experiments were similar to those obtained when using non-activated saponite.     

Brønsted acid catalyzed enantioselective α-amidoalkylation in the synthesis of isoindoloisoquinolines

The Parham cyclization-intermolecular α-amidoalkylation sequence results in the facile enantioselective synthesis of 12b-substituted isoindoloisoquinolines (ee up to 95%) using BINOL-derived Br?nsted acids. α-Amidoalkylation of indole occurs through the formation of a chiral conjugate base/bicyclic quaternary N-acyliminium ion pair.     

An immunochemical strategy based on peptidoglycan synthetic peptide epitopes to diagnose Staphylococcus aureus infections

The characteristic pentaglycyl cross-bridge of the Staphylococcus aureus peptidoglycan (PG) cell wall component is an attractive epitope to raise specific antibodies against this microorganism. Based on this approach, we report here for the first time a competitive ELISA able to detect S. aureus down to 10⁴ CFU mL⁻¹, without pre-enrichment on cell culture. The antibodies were raised against peptide-protein bioconjugates prepared by covalently coupling peptide haptens (PSau6 and PSau8) designed and synthesized taking into consideration the complex tridimensional structure in the PG polymer. Deglycosylation of the PG under acidic conditions has found to increase assay detectability. Assay performance has been evaluated in clinical samples such as bronchoalveolar lavage (BAL) and bronchoalveolar endotracheal aspirates (BAS) showing promising results for further implementation of this immunoassay as a daily routine diagnostic tool. Cross-reactivity studies have demonstrated that the immunoassay is specific for S. aureus.     

Targeted analysis with benchtop quadrupole–orbitrap hybrid mass spectrometer: Application to determination of synthetic hormones in animal urine

Sensitive and unequivocal determination of analytes/contaminants in complex matrices is a challenge in the field of food safety control. In this study, various acquisition modes (Full MS/AIF, Full MS + tMS/MS, Full MS/dd MS/MS and tSIM/ddMS/MS) and parameters of a quadrupole–orbitrap hybrid mass spectrometer (Q Exactive) were studied in detail. One of the main conclusions has been that, reducing the scan range for Full MS (using the quadrupole) and targeted modes give higher signal-to-noise (S/N) ratios and thereby better detection limits for analytes in matrix. The use of Q Exactive in a complex case, for the confirmatory analysis of hormones in animal urine is presented. A targeted SIM data dependent MS/MS (tSIM/ddMS/MS) acquisition method for determination of eight synthetic hormones (trenbolone, 17α ethinylestradiol, zeranol, stanozolol, dienestrol, diethylstilbestrol, hexestrol, taleranol) and a naturally occurring hormone (zearalenone) in animal urine were optimized to have sensitive precursors from targeted SIM mode and trigger MS/MS scans over the entire chromatograph peak. The method was validated according to EC/657/2002. CCα (decision limit) for the analytes ranged between 0.11 μg L⁻¹ and 0.69 μg L⁻¹ and CCβ (detection capability) ranged between 0.29 μg L⁻¹ and 0.90 μg L⁻¹.