Properties of novel aldose reductase inhibitors, M16209 and M16287, in comparison with known inhibitors, ONO-2235 and sorbinil

Properties and efficacies of novel aldose reductase (AR) inhibitors, M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) and M16287 (1-(3-chlorobenzo[b]furan-2-ylsulfonyl)hydantoin), were examined in vitro and in vivo, compared with known AR inhibitors, ONO-2235 and sorbinil. These four compounds inhibited partially purified aldose reductases from various origins, and the potencies of M16209 and M16287 were on the whole similar to ONO-2235, and were greater than that of sorbinil. The IC50 values of the four AR inhibitors did not substantially depend on the substrate used. Kinetic studies of inhibition of partially purified bovine lens (BLAR) revealed that M16209, M16287 and sorbinil were uncompetitive with glyceraldehyde and noncompetitive with nicotineamide adenine dinucleotide phosphate (NADPH), whereas ONO-2235 was noncompetitive with both glyceraldehyde and NADPH. Aldose reductase became less sensitive to the four inhibitors as enzyme purification progressed, although the susceptibility to inhibition was partially reversed by incubation with dithiothreitol. In addition, the four compounds slightly affected those enzymes of carbohydrate and glutathione metabolism which were tested. M16209 and M16287 prevented sorbitol accumulation in isolated rat tissues as potently as ONO-2235 and sorbinil. M16209 and M16287 were effective in the prevention of galactosemic cataracts and amelioration of diabetic neuropathy with almost the same potency, while ONO-2235 was effective only in neuropathy, and sorbinil was effective in galactosemic cataracts and diabetic neuropathy with a different potency. These results indicate that M16209 and M16287 are potent aldose reductase inhibitors, which could be applicable to treatment for diabetic complications.     

Preparation of zein microspheres conjugated with antitumor drugs available for selective cancer chemotherapy and development of a simple colorimetric determination of drugs in microspheres

Zein microspheres conjugated with antitumor drugs (mitomycinc (MMC), daunomycin hydrochloride (DM), peplomycin sulfate (PEP] were prepared by using a dimethyl sulfoxide (DMSO)-H2O system. MMC with low solubility in H2O was easily entrapped by the standard procedure, whereas some modifications were required for moderately and highly soluble drugs such as DM and PEP. Colorimetric determination of the drugs in microspheres was easily achieved by use of the phenol-sulfuric acid method for drugs with sugar moieties in their molecules, such as DM and PEP, while a simple treatment of the microspheres with concentrated sulfuric acid was applied in the case of drugs having a chromophore in their molecules, such as DM and MMC.     

Syntheses of 3-substituted furans via lithium di(3-furyl)cuprate—the application of lithium di(3-furyl)cuprate to the total synthesis of dendrolasin

One step syntheses of 3-substituted furans by the reactions of a new reagent, lithium di(3-furyl)cuprate $\text{1}$, with various substrates and the application of $\text{1}$ to a total synthesis of dendrolasin are described.     

Synthesis of 4,5-diaminopyrrolo[1,2-a]quinoline derivatives by annulation of N,N-dialkyl[2-(pyrrol-1-yl)benzylidene]ammonium salts in the presence of an isocyanide

A facile synthetic method for 4,5-diaminopyrrolo[1,2-a]quinoline derivatives has been developed. Treatment of 2-(pyrrol-1-yl)benzaldehydes with secondary amine hydrochloride/NaI/TMSCl/Et₃N in the presence of an isocyano compound leads to the formation of 4-alkyl(or aryl)amino-5-dialkylaminopyrrolo[1,2-a]quinolines.     

Studies on macrolide antibiotics I. Synthesis and antibacterial activity of erythromycin A 9-O-substituted oxime ether derivatives against Mycobacterium avium complex

A series of erythromycin A 9-O-substituted oxime ether derivatives have been synthesized and evaluated for antibacterial activity against Mycobacterium avium complex (MAC) and Staphylococcus aureus. These compounds possessed stronger in vitro activity against MAC including macrolide-resistant strains than clarithromycin (2), although in vitro antibacterial activities of these compounds were less than that of 2 against Staphylococcus aureus. Our studies found that several factors contribute to the antibacterial activity against MAC. The length and spatial orientation of the substituent at 9-position were found to significantly influenced the anti-MAC activity, especially against macrolide-resistant strains. Of all the compounds prepared, erythromycin A 9-[O-(4-phenylbutyl)oxime] (12q) and erythromycin A 9-[O-(3-phenoxypropyl)oxime] (12t) possessed 16 times stronger antibacterial activity than 2 against clarithromycin-resistant strains. Surprisingly, the minimum inhibitory concentrations (MICs) of 12q and 12t against the resistant strains were almost same as those against the susceptible strains. These results suggest that the erythromycin A 9-O-substituted oxime ether derivatives would be promising macrolide antibiotics.     

Solvent extraction of alkali metal ions with chromium complexes

Solvent extraction of alkali metal ions by batch and counter-current distribution methods was investigated with tetrathiocyanatodiamminechromate(III) and tetrathiocyanatodianilinechromate(III) as reagents and nitromethane and nitrobenzene as organic solvents. The distribution ratios of alkali metal ions in the various systems were measured. Cesium was readily extracted with the aniline compound and nitrobenzene. The separation of sodium from potassium in trace amounts was possible by the counter-current distribution method.     

Convenient synthesis of 3,3,3-trifluoropropenyl compounds from aromatic aldehydes by means of the TBAF-mediated Horner reaction

A simple synthesis of 3,3,3-trifluoropropenyl compounds by means of the TBAF-mediated Horner reaction is described. The reagent, 2,2,2-trifluoroethyldiphenylphosphine oxide, was readily prepared either by Arbuzov reaction of ethyl diphenylphosphinite with 2,2,2-trifluoroethyl iodide or by treating chlorodiphenylphosphine with trifluoroacetic acid and water. Treatment of the phosphine oxide with aromatic aldehydes in the presence of TBAF at room temperature afforded the corresponding 3,3,3-trifluoropropenyl compounds in good yields. The present method is very convenient for preparing 3,3,3-trifluoropropenyl compounds from aromatic aldehydes in terms of availability of the reagent, operational simplicity, and good yields of the products.     

Emission-spectrometric determination of trace non-rare earth elements in yttrium oxide using AgF-Ga2O3 mixed carrier

Summary An emission-spectrometric method is described for the quantitative determination of traces of non-rare earth elements in yttrium oxide, employing addition of AgF-Ga₂O₃ mixed carrier. This addition effects an increase of the rate of evaporation of the analytical elements and of the number of atoms in the arc plasma. It enhances the sensitivity of the analytical elements to a larger extent than other carriers and permits the determination of microquantities of the elements (Mg, Ca, Mn, Co, Fe, Pb, Cu, Cd, Al, B, Sn, As, Bi) within limits of detection from 0.1 to 13 ppm in high-purity yttrium oxide. The coefficients of variation are less than 20%.

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Emissionsspektrometrische Bestimmung von nicht zu den Seltenen Erden gehörenden Elementspuren in Yttriumoxid mit Hilfe eines AgF-Ga₂O₃ -Trägergemisches

Zusammenfassung Das Trägergemisch bewirkt eine Erhöhung der Verdampfungsgeschwindigkeit der zu bestimmenden Elemente und der Anzahl der Atome im Bogenplasma. Es verbessert mehr als andere Träger die Empfindlichkeit und ermöglicht die Bestimmung von Mikromengen der Elemente (Mg, Ca, Mn, Co, Fe, Pb, Cu, Cd, Al, B, Sn, As, Bi) in hochreinem Yttriumoxid mit Nachweisgrenzen von 0,1–13 ppm. Die Variationskoeffizienten liegen unter 20%.

     

Radical [3 + 2] cycloaddition reaction with various alkenes using iodomethylcyclopropane derivatives as new homoallyl radical precursors

Radical iodine atom transfer [3 + 2] cycloaddition with various alkenes using dimethyl 2-(iodomethyl)cyclopropane-1,1-dicarboxylate and 1,1-bis(phenylsulfonyl)-2-(iodomethyl)cyclopropane as new precursors of a homoallyl radical species smoothly proceeds to give functionalized cyclopentane derivatives in good yields.