A chemical bond has the hard-soft dissymmetry as well as the charge dissymmetry. Thus, a combination system of a hard acid and a soft nucleophile is able to cleave the bond which consists of a hard base and a soft acid. Recently, the author has developed a number of combination systems for the cleavage reactions of various bonds. This article describes the cleavage reaction of C-O, C-halogen, C-NO2, C-S, and C=C bonds with a combination system consisting of a hard Lewis acid and a soft nucleophile.
The essential oils from leaves and rootlets of Cinnamomum sieboldii MEISN.[=C. loureirii auct. Jap. non NEES] (Lauraceae) were examined by using gas chromatography, gas chromatography-mass spectry and infrared. The abundant existence of linalool (20.6-37.4% in the oils), cinnamaldehyde (10.0-25.9%), citral-a (5.5-11.9%), citral-b (2.9-5.8%) 1, 8-cineole (2.0-8.2%), and geraniol (1.3-3.3%) was characteristic of the leaves oils (samples I-IV). While, rootlet oils (samples I and II) contain cinnamaldehyde (69.1 and 81.0% in the oils respectively), coumarin (7.8 and 1.1%) and camphor (8.4 and 1.0%) predominantly.
A new benzoquinone, kushequinone A (I), a new flavanonol, kushenol N (II), and a new isoflavone glycoside, kushenol O (III), were isolated from the dry roots of Sophora flavescens AIT. (Leguminosae). Their structures were elucidated on the basis of spectral data especially 1H nuclear magnetic resonance and 13C nuclear magnetic resonance. A benzoquinone derivative was isolated for the first time from Sophora flavescens AIT.
Bis(alkylaminoalkoxy-2-benzofuranyl)ketone (IIa-o) were synthesized by the reaction of alkylaminoalkyl halide with bis(hydroxy-2-benzofuranyl)ketones (I). Bis(alkylaminoalkoxy-2-benzofuranyl)keton N, N-dioxides (IIIa, b) were prepared from II by treatment with hydrogen peroxide. Bis(acyloxy-2-benzofuranyl)ketones (IVa-q) were synthesized by the reaction of acid chloride and acid anhydride with I. Bis(6-acetoxy-2-benzofuranyl)ketone (IVb) showed the most potent inhibitory activity on the multiplication of influenza virus in vitro. Bis(7-diethylaminoethoxy-2-benzofuranyl)ketone N, N-dioxide (IIIa) showed a potent interferon inducing activity in mice. IVb and IIIa given orally were effective against the infection of an influenza virus in mice.
5-Dimethylaminonaphthalene-1-sulfonyl azide (II) was synthesized as a labeling reagent for activated olefins (norbornenes, dihydropyrans and enamines) for use in high-performance liquid chromatography (HPLC) with fluorescence detection. Treatment of 5-dimethylaminonaphthalene-1-sulfonyl chloride (I) with sodium azide gave II in a 81% yield. These olefins were labeled with II in organic solvents such as toluene, acetonitrile and methanol, and chromatographed on a reversed-phase HPLC column (mobile phase : methanol-water and acetonitrile-water) with fluorescence detector. The detection limits of test samples, N-octyl-5-norbornene-2, 3-dicarboximide, 3, 4-dihydro-2-ethoxy-2H-pyran and 1-pyrrolidino-1-cyclohexene, were 80 pg, 1 ng, 80 pg/10 μl on labeling with II, respectively.
An improved method for the determination of hydroxyproline (Hyp) in animal tissues has been established by modifying Kivirikko's and KISO methods. This method consists of the oxidation of Hyp by the addition of chloramine T at 0°C for 2 h in 0.5 M borate buffer (pH 8.2) containing 1 M KCl. It was confirmed that Hyp was satisfactorily oxidized to an oxidation intermediate, which was stable throughout the process of the oxidation at 0°C for 2 h. The degree of color development with the colorimetric reagent in this method was 2-3 times higher than that in conventional methods, and the reproducibility was invariably good. The present method is very useful for the microanalytical determination (0.05-4 μg/tube) of Hyp.
The percutaneous absorption of indomethacin (ID) from five kinds of fatty alcohol and propylene glycol (FAPG) bases consisting of a mixture of fatty alcohol (FA) and propylene glycol (PG) was studied by using the depilated abdominal skin of rats. The percutaneous absorption of ID from No. 1 base consisting of stearyl alcohol (SOH) and 75% of PG was slightly higher than that of No. 2 base consisting of SOH and 66.7% of PG. The absorption of ID from No. 3 base consisting of SOH and 50% of PG was significantly lower than those of Nos. 1 and 2 bases. It became evident that the amount of ID absorbed in cutis from FAPG base and the release rate of ID in vitro tended to increase as the content of PG in FAPG increased. Furthermore, in Nos. 1, 2, and 3 FAPG bases, it was observed that the viscosity of base also exerted an influence on the percutaneous absorption and release rate of ID. The viscosity of No. 4 base consisting of cetyl alcohol (COH) and 75% of PG was almost the same as No. 1 base, whereas the percutaneous absorption of ID from the former was lower than that of the latter. The viscosity of No. 5 base consisting of SOH and COH (a mixing rate of 1 : 1) and 75% of PG was higher than that of No. 4 vase. However, the percutaneous absorption of ID from both bases was almost the same. It was found that the percutaneous absorption of ID from FAPG base containing different kinds of FA in a given volume of PG was not affected by the viscosity of base. Moreover, it was cleared from further experiment that the partition ratio of ID between water and FAPG base exerted an influence on the percutaneous absorption of ID.
When 5, 6-diphenyl-1, 2, 4-triazine-3-thiol was heated in methanol or ethanol under neutral conditions, the addition of methanol or ethanol across the N4-C5 bond occurred to give the corresponding 5-alkoxy-4, 5-dihydro-5, 6-diphenyl-1, 2, 4-triazine-3-thiol. Such reaction was not observed in 1-butanol. When the triazine derivative refluxed in 2-propanol, bis(5, 6-diphenyl-1, 2, 4-triazin-3-yl) disulfide was obtained instead of the expected addition compound. Structurally similar compounds, 3-methylthio-5, 6-diphenyl-1, 2, 4-triazine and 6-methyl-5-phenyl-1, 2, 4-triazine-3-thiol did not undergo such reaction. The synthesized compounds were examined mainly for activities against influenza viruses. 3-Mercapto- and 5-alkoxy-4, 5-dihydro-3-mercapto-5, 6-diphenyl-1, 2, 4-triazines exhibited 50% inhibitory concentrations of 12.5-63.1 μg/ml (Index 12.6-63.5) against influenza viruses such as A0/PR-8, A1/FM-1, A1/Fukuoka, A2/Adachi, A2/Aichi, B/Lee, B/Kagoshima and Horse/Miami in the chorio-allantoic membrane culture.
Microencapsulation of sulfamethizole by using Eudragit RS was investigated by the evaporation process in water phase. Some metal stearates were used to reduce the flocculation of microcapsules in the preparation. However, the microcapsules just after separated from the water phase were swollen. The minimum swelling ratio was obtained in the case of aluminium tristearate. Therefore, the use of aluminium tristearate as an additive was found to be most suitable for the microencapsulation by using Eudragit RS. Furthermore, an optimum amount added was found to exist for each of the metal stearates in this experiment. The microcapsules obtained after drying under reduced pressure were uniform and free-flowing particles. The dissolution rates of sulfamethizole from these microcapsules were relatively reduced compared to that from sulfamethizole powders.
The stability of disodium latamoxef in aqueous solution and compatibility in 5% glucose solution at 25°C were studied. Disodium latamoxef for injection was found to be composed of R(-)-epimer and S(+)-epimer in the ratio of 1 : 0.91. The hydrolysis rates of both epimers were identical and the pH-rate profile was obtained. The rate law describing water-catalyzed hydrolysis of each molecular species and hydroxide ion-catalyzed hydrolysis of di- and tri-anions gave the best fits to the experimental results. The apparent activation energies at pH 3.0, 6.0 and 9.0 were 16.5, 19.2 and 27.1 kcal mol-1, respectively. The 10% loss time (t0.9) at pH 4-7 and 25°C was predicted to be 30-33 h. The remaining ratios at 6 and 24 h were predicted to be 98.1 and 92.6%, respectively. The stability in the admixture was almost similar to the predicted values, suggesting that pH is a primary factor. For the additives studied, it was concluded that the admixture of 5-fluorouracil injection should be administered within 6 h and tegafur injection (Futraful〓) is incompatible.
We have developed a new inhalation and infection apparatus for screening of antiviral agents against influenza viruses. By use of this apparatus, mice can be infected with the aerosolized influenza virus more quantitatively than by an ordinary nasal-drop infection. When mice were inhalated with the aerosolized influenza virus (A/PR/8/34H0N1), changes of body weight, lung consolidation, and mortality markedly depended on viral doses in the infected mice, as compared with nasaldrop infection that allows fluctuations in these indicators and requires a great deal of skill. Furthermore, an occurrence of nonspecific inflammation in the lung of nasally drop-infected mice was greatly reduced by use of the new apparatus. When anti-viral activities of known anti-influenza agents (amantadine and ribavirin) and unknown herb extract (TJN-800) were tested in mice infected with the aerosolized influenza virus, these compounds showed a protecting activity against influenza virus. As a result, aerosolized infection of influenza virus to mice by using our apparatus is superior in the reproducibility and quantitativeness of the experiments to nasal-drop method.
The synthesis and absolute stereochemistry of (-)-R-1-(4-hydroxyphenyl)-2-[(3, 4-dimethoxyphenethyl)amino]ethanol (denopamine), a new potent cardiotonic agent, are described. Racemic 1-(4-benzyloxyphenyl)-2-[(3, 4-dimethoxyphenethyl)amino]ethanol (dl-9), a precursor of denopamine, was synthesized by various methods in good yields. Optical resolution of dl-9 with N-acetyl-D-phenylalanine followed by debenzylation gave denopamine in a 85% yield. The absolute stereochemistry of denopamine was determined to be R by X-ray crystallographic analysis.
Effects of nicergoline, a cerebral circulation and metabolism ameliorator, on cerebral energy metabolism were studied in normal mice by measuring contents of several major metabolites (creatine-P, adenosine triphosphate, glucose, glycogen, lactate and pyruvate) in the brain 30 min after intraperitoneal administration of the drug at doses of 1, 4 and 16 mg/kg and compared with those of dihydroergotoxine (DHE). In addition, influences of both drugs on cytochrome oxidase activity in normal mouse brain homogenate were studied in vitro. Both of nicergoline and DHE caused 12-20% increases in creatine-P contents and 10-37% decreases in lactate and pyruvate contents, but had no effect on glucose contents and energy reserve values. In vitro studies revealed that nicergoline had more potent activating action on cerebral cytochrome oxidase than DHE at final concentrations of 10 and 100 μM. These results suggest that nicergoline has a promoting action, similar to DHE, on cerebral energy metabolism of normal mouse.
Enzymatic assay, by use of casein as substrate, has long been used for the quantitative determination of serrapeptase. The method, however, either requires a complicated operation or results with poor reproducibility and low sensitivity. Therefore, we tried to investigate a method for the determination of serrapeptase by using high performance steric exclusion chromatography (SEC). An organic microparticulate stationary phase (diol bonded silica gel), an aqueous mobile phase and ultraviolet detection at 278 nm were adopted. Consequently, we found a linear relationship between SEC method and conventional enzymatic assay. Simultaneously, the molecular weight of serrapeptase was estimated from calibration curve of SEC. As the result, the new SEC method may be superior to the alternate techniques for the determination of serrapeptase.