Synthesis of 2-(p-R-benzoylmethylene)-3-(p-R-phenyl)-1H-quinoxalines

The reaction of 1,2-diaminobenzenes with substituted 1,2-dibenzoyl-1,2-dibromoethanes constitutes a convenient synthetic route to the hitherto 2-(p-R-benzoylmethylene)-3-(p-R-phenyl)-1H-quinoxalines. Structures of all products were elucidated by ir, ¹H and ¹³C-nmr, mass spectra data. X-Ray crystallography data confirm assigned structures.     

Synthesis of Novel Pyrrolo-[3,2-c]quinolines via Iron-Catalyzed Cross-Coupling Reaction of Grignard Reagents

Cross-coupling reaction of alkyl and aryl magnesium halides with 4-chloro-pyrrolo-[3,2-c]quinoline in the presence of a catalytic amount of iron salt is described. The reactions are completed in 30 min, resulting in moderate to excellent yields of 52–94% in a tetrahydrofuran (THF)–N-methylpyrrolidinone (NMP) solvent mixture.     

An Improved Pinacol Rearrangement for the Synthesis of 2-Alkyl-1, 3-Cyclopentanediones

2-Methyl, 2-ethyl and 2-isopropyl-1,3-cyclopentanediones are prepared by a modification of the method described by Nakamura, et. al.¹     

Synthesis of (22R, 25R)-3β,26-Dihydroxy-5α-furostan-6-one #

The synthesis of a plant growth promoter furostanol which bears the characteristic functionality of teasterone on rings A and B is described.

     

Fluoroquinolone Antimicrobials: Singlet Oxygen, Superoxide and Phototoxicity

The fluoroquinolone antibacterial agents possess photo-sensitizing properties that lead to phototoxic responses in both human and animal subjects. The phototoxicity order reported in humans is: fleroxacin > lomefloxacin, pefloxacin > ciprofloxacin ? enoxacin, norfloxacin and ofloxacin. Studies both in vivo and in vitro have related this phototoxicity to the generation of reactive oxygen species including hydrogen peroxide and the hydroxyl radical. We determined the quantum yields of singlet oxygen generation (φ_Δ,) by detection of the singlet oxygen (¹O₂) luminescence at 1270 tun for several fluoroquinolones, naphthyridines and other structurally related compounds. All the fluoroquinolones examined have low φ_Δ values ranging from 0.06 to 0.09 in phosphate buffer at pD 7.5. We also determined the ¹O₂ quenching constants for these compounds and their values were on the order of 10⁶M^?1 s¹, except for lomefloxacin whose rate constant was 1.8 × 10⁷M^?1 s^?1. The φ_Δ values were significantly decreased in a solvent of lower polarity such as methanol (0.007 ≤φ_Δ≤ 0.02). The production of ¹O₂ by these antibiotics did not correlate with the order reported for their phototoxicity. We also measured the photogeneration (λ > 300 nm) of superoxide by these antibacterials in dimethylsulfoxide using electron paramagnetic resonance and the spin trap 5,5-dimethyl-l-pyrroiine N-oxide. Although there is not a one-to-one correspondence between the relative rates of superoxide generation and the phototoxicity ranking of the fluoroquinolones, the more phototoxic compounds tended to produce superoxide at a faster rate. Nevertheless, the magnitudes of the observed differences do not appear sufficient to explain the range of fluoroquinolone phototoxicity potencies in human and animal subjects in general and the high activity of fleroxacin and lomefloxacin in particular. For these latter drugs the photoinduced loss of the F₈ atom as fluoride and the concomitant generation of a highly reactive carbene at C-8 provide a more plausible mechanism for their potent phototoxic and photocarcinogenic properties.     

Simplified procedures for the analysis of polycyclic aromatic hydrocarbons in water, sediments and mussels

We describe in this paper simple and robust analytical protocols to determine the 16 polycyclic aromatic hydrocarbons (PAHs) of the US Environmental Protection Agency priority list in water, sediment and mussels. For water samples, eight different solid-phase extraction (SPE) sorbents have been compared and among them, C18 provided highest recoveries and limits of detection of 0.3-15 ng/L. For lyophilized sediments, Soxhlet and ultrasonic extraction were compared, and the last one permitted to recover all analytes with highest repetitivity and was validated by analysing a certified reference material. Finally, the analysis of mussels was undertaken using Soxhlet, ultrasonic and pressurized liquid extraction (PLE) and the performance of several clean-up steps are compared. Whereas for the former two, incomplete recovery or losses of some analytes were evidenced, PLE permitted a more efficient extraction and although alkaline digestion was necessary to remove coextracted compounds, the method gave acceptable recoveries and limits of detection of 0.5-7.7 microg/kg dry mass, as for sediments. In all cases, analysis was performed by gas chromatography coupled to mass spectrometry and internal standard quantification was performed using five deuterated PAHs. Each method performance is discussed for the three matrices analysed and the paper reports advantages and disadvantages of each for their routine application in monitoring programs.     

Solid-phase synthesis of arginine-containing peptides and fluorogenic substrates using a side-chain anchoring approach

Attachment of an amino acid to a solid support by its side chain is sometimes necessary to take advantage of an alpha-carboxylic group available for diverse modifications, including the incorporation of a fluorophore for the preparation of fluorogenic substrates. In contrast to most other amino acids, anchoring the guanidinium group of an arginine to a resin requires the use of a supplementary linker. To avoid the usually multistep synthesis of such a linker as well as its difficult attachment to the guanidine group, we developed a simple method where the guanidine group is built on a Rink amide resin. Our strategy followed the steps of guanidine formation: (i) addition of an isothiocyanate derivative of ornithine to the amino group of a solid support, yielding Nomega-linked thiocitrulline; (ii) S-methylation of thiourea; (iii) guanidinylation using ammonium acetate. Cleavage of the resin generated the arginine-containing compound, the amine group of the resin becoming part of the guanidine. We have demonstrated the usefulness of this method by the synthesis of a series of fluorogenic substrates for trypsin-like serine proteases, which were obtained in high yield and purity. Then, our strategy also allowed generation from the same precursor differentially substituted arginine derivatives, including Nomega-methyl- and Nomega-ethylarginines. The ability to prepare such analogues together with the intermediates thiocitrulline and S-methylisothiocitrulline from a unique precursor while the alpha-amine and carboxylic groups remain available for modification also makes this method a powerful tool for combinatorial solid-phase synthesis of NO synthase inhibitors.     

Photostabilization study of ethylene-butyl acrylate copolymers functionalized in the molten state with hindered amine light stabilizers (HALS)

Hindered Amine Light Stabilizers (HALS), N-methylated and O-alkylhydroxylamine, were successfully anchored onto an ethylene-co-butyl acrylate (BA) by a transesterification reaction in the molten state. The content of HALS bonded to the EBA was calculated from the atomic ratio (N/C) determined by X-ray Photoelectron Spectroscopy (XPS). After reaction times of 5–30 min in the molten state the content of bonded HALS attained values from 0.17 to 0.63%. The modified EBA with HALS were studied by Chemiluminescence emission and the photostabilization effect was evaluated under accelerated ageing in the presence of pesticides. The antioxidant effect of HALS bonded to EBA was evaluated by determination of Carbonyl Index (CI) and retention of elongation at break as a function of exposure time and pesticide treatment. The stability of the EBA with anchored HALS exhibited higher performance as shown by low CI-values and correlated with the content of bound HALS and the thermal history of the materials. Also, mechanical properties correlated well with the CI results and the photostabilization of bound HALS was effective until 3150 h of exposure time using pesticides.     

3,5-Bis(ferrocenylmethylene)-1-methyl-4-methylenepiperidine. Synthesis and some chemical properties

3,5-Bis(ferrocenylmethylene)-1-methyl-4-methylenepiperidine, a diferrocenyltriene with a fixeds-cisoid conformation of the exocyclic double bonds, was synthesized. On heating, this compound cyclodimerizes according to the [4+2]-cycloaddition scheme; it forms Diels-Alder adducts with azodicarboxylic and maleic acidN-phenylimides. The compound easily cyclodimerizes in the presence of acids by a proton cyclodimerization mechanism to give a spiro cyclodimer. The triene also adds a 3,5-bis(ferrocenylmethylene)-1,4-dimethyl-1-azonia-4-cyclohexyl salt to the terminal methylene group yielding linear and cyclic addition products. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 511–516, March, 2000.