The title acyl or silyl group transfer reactions under neutral or nearly neutral conditions can be classified into the following two types: i) simple acyl/proton or silyl/proton exchange reactions of H-acidic materials such as amines, alcohols, carboxylic acids, mercaptans, phenols, and imides accompanied by volatile alkyl acetates (type I reaction), and ii) aldol or Michael additions of alkyl acetate anions to carbonyl compounds accompanied by a silyl group transfer on the oxygen atom of carbonyl groups (type II reaction). Synthetic reagents utilizing these reactions, e. g., alkoxycarbonylation, Semmler-Wolff aromatization, silylation, silylenation, Pummerer-type rearrangement, acid anhydride or amide formation are discussed. Applications of these reagents or reactions to the synthesis of biologically important natural products, methyl jasmonates, 2-deoxy-D (and L)-riboses, and anthracyclines are also described.
The phase-transition temperatures, T*, molar enthalpies, ΔH2*, and molar heat capacities, ΔCp, of pure cholesteryl esters, i. e. myristate (ChM), palmitate (ChP) and oleate (ChO), were measured by using a differential scanning calorimeter. The observed kinds of transition were crystal (k)/smectic phase (s), s/cholesteric phase (c), and c/isotropic phase (i) for ChM, k/c and c/i for ChP, and k/i transition for ChO, respectively. From the values of T*, ΔH2*, and ΔCp, the values of T* and ΔH2* of k/i transition for ChM and ChP were theoretically estimated. The molar transition enthalpies of the k/i transition, which occurs at the co-existence of solute (cholesteryl ester) and its solution with solvent, were also calculated for ChM, ChP and ChO at 298.15 K. By use of the above quantities, the solubility vs. temperature relationship of cholesteryl ester in ethanol, 1-pentanol, acetone, toluene and carbon tetrachloride was analyzed thermodynamically as well as in terms of regular solution theory. The activity coefficient of cholesteryl ester, f2, the product of solution lattice coordination number and solute-solvent interaction energy, zw, and the solubility parameter of cholesteryl ester, δ2, were estimated at 298.15K. Toluene and carbon tetrachloride were almost ideal solvents. The values of δ2 at 298.15 K were 18.0, 17.8, and 14.8 J1/2. cm-3/2 for ChM, ChP, and ChO, respectively.
1-Amino-3-(substituted benzenesulfonyl) guanidines and 3-(substituted benzenesulfonylamino)-5, 6-disubstituted-1, 2, 4-triazines were synthesized, and examined for their activities against influenza virus A2/Adachi strain and micro-organisms parasitic to animals. 3-(4-Fluoro-, 4-amino-, 3-amino-, 3-nitro, 2, 5-dichloro-, and 2, 5-dimethyl-benzenesulfonylamino)-5, 6-dipheny1-1, 2, 4-triazines were highly active against the influenza virus. Their 50% inhibitary concentrations were 6.25-15.7 μg/ml and 50% virucidal cancentratians were 14.7-17.7μg/ml. Satisfactoryregression equations were obtained for inhibitory and virucidal activities and toxicity to chorio-allantoic membrane. It is inferred from the equations that the introduction of electron-donating groups on benzene ring of benzenesulfonyl moiety in 1, 2, 4-triazines and the presence of tetramethylene group on 1, 2, 4-triazine ring enhance the inhibitory and virucidal activities. The majority of 1, 2, 4-triazines showed minimum inhibitory concentrations of 50-100μg/ml against Mycoplasma gallisepticum and 12.5-100μg/ml against Pasteurella. 1-Amino-3-(substituted benzenesulfonyl) guanidines, however, showed weak activities against both the influenza virus and micro-organisms.
The components of the roots of Cassia obtusifolia L. were examined. As a result, nine anthraquinones [islandicin (1), helminthosporin (2), chrysophanol (3), physcion (4), xanthorin (5), 8-O-methylchrysophanol (8), obtusifolin (6), emodin (12), and aloe-emodin (14)], a naphtho-γ-pyrone [rubrofusarin (6)], a benzoquinone [2, 5-dimethoxybenzoquinone (11)], phytosterols (7), and betulinic acid (10) were isolated. Compounds 2, 8, 10, and 11 are new components from this plant. Compounds 11 and 14 isolated from the roots and isotoralactone (22), toralactone (23), questin (15), and torosachrysone (24) from the seeds showed antimicrobial activities.
Polysaccharides fractionated from the mycelia of Poria cocos (PCME) were evaluated for antitumor activity against several mouse tumors. PCME administered intraperitoneally, but not orally, inhibited markedly the growth of sarcoma 180 and Ehrlich carcinoma implanted subcutaneously. In the inhibition of the growth of these two tumors, PCME were more effective than Krestin (PSK). PCME administered intraperitoneally increased somewhat the lifespan of mice inoculated intraperitoneally with IMC carcinoma and sarcoma 180, but were found to be inactive against intraperitoneally-implanted L1210 leukemia, P388 leukemia and B16 melanoma. These results indicate that against mouse tumors, PCME have similar antitumor spectrum to other polysaccharides such as PSK or lentinan.
To prepare the ointment of antibiotic negamycin (NGM), the release behavior from various ointment bases, antimicrobial activity, and chemical stability of NGM were investigated. In vitro release of NGM from gel base was greater than that from hydrophilic ointment JPX and white petrolatum containing 5 w/w% liquid paraffin. The release rate and the amount of NGM released from the gel base were found to increase in proportion to the content of Hiviswako No.104 in the ointment. NGM was much more stable in gel base than in hydrophilic ointment JPX, though it was decomposed under pseudo-first-order kinetics in both ointment bases. Antimicrobial activity of NGM ointment was evaluated by the cup-plate method, suggesting a sufficient efficacy of NGM for the treatment of infectious diseases caused by gram-positive or gram-negative bacterium. The present data suggest the possible utility of gel base in preparation of NGM ointment.
To improve stability and antimicrobial activity of negamycin (NGM) in ointment preparation, chemical stability and in vitro release of NGM incorporated in ointment cking water phase and the combination effect of NGM and other antibiotics were investigated. In vitro release of NGM from fatty alcohol and propylene glycol base was greater than that from plastibase 50W and hydrophilic poloid. The release rate of NGM was further improved by modifying ingredients and compositions of FAPG base. The combinations of NGM and other antibiotics significantly improved antimicrobial activity against gram-positive bacterium, particularly the combination of NGM and tetracycline. The present data suggest the utility of FAPG base and the efficacy of the combination of NGM and tetracycline in the preparation of NGM ointment.
At a dose of 100 mg/kg of cimetidine, the area under the plasma concentration per unit dose (AUC/D) was somewhat larger than those of other doses (12.5, 25, and 50 mg/kg) following bolus intravenous injection in rats. To clarify this phenomenon, the maximum velocity of secretion (Vmax) and the Michaelis constant (Km) for renal excretion were estimated by use of the standard renal clearance method. On the basis of these parameters, the disposition of cimetidine was analyzed by the non-linear 2-compartment model including the tubular secretion process. The observed values of the plasma concentration profile and urinary excretion rate agreed well with the calculated values. Vmax (588.2μg/min/kg) and Km (39.21μg/ml) obtained by the standard renal clearance method were not greatly different from Vmax (397.8μg/min/kg) and Km (62.12μg/ml) obtained by the nonlinear compartment analysis, and the reliability of the model was confirmed. The simulated plasma concentrations based on the linear 2-compartment model agreed well with the values which were simulated based on the non-linear model at doses of 12.5, 25, and 50 mg/kg. Consequently, it is obvious that the disposition of cimetidine following intravenous injection can be approximated as a linear process under the doses of 50 mg/kg. However, at the dose of 100 mg/kg the simulated values based on the linear model were underestimated for the values obtained from non-linear model, and in these cases the approximation of disposition of cimetidine as a linear process will produce an error.
In order to estimate trace amounts of batroxobin, a defibrinogenating agent, we established sandwich enzyme immunoassay of this substance in the plasma sample. The Fab' fragment was labeled with horseradish peroxidase by using 4-(maleimidomethyl)-cyclohexane-1-carboxlic acid succimide ester as a coupling reagent. The conjugate thus obtained could be used to determine batroxobin concentration in the plasma sample up to 25 pg/tube (minimum detectable concentration) with the variable coefficient of 8.4%(within-run) and 13.8%(between-run). It was observed that the recovery of batroxobin from the plasma in several animal species ranges from 25% to 90%, when determined by this method. Satisfactory result was obtained by treatment of plasma with diisopropylfluorophosphate or by fibrinolysis with urokinase.
We have already established enzyme immunoassay for microanalysis of batroxobin. In this paper, we determined the concentration of batroxobin in the plasma and the urinary excretion of batroxobin in human after the drop infusion by using this method. In the single administration (0.27 BU/kg), the half-life of batroxobin in the plasma was 6.4h. In the first run of the repeated administration (0.11 BU/kg each), it was also 5.9 h. However, the second and third runs led to a shortening of the half-lives. The cumulative urinary excretion was 0.30% of the dose given by the single administration, and 0.07% by the repeated administration. It was found that there was a linear relationship between body weight and elimination rate constant of human and some laboratory animals. After the single administration of batroxobin, it was also observed that fibrinopeptide A and Bβ1-42 were immediately liberated, with a decrease in fibrinogen in the plasma, followed by an increase in fibrin degradation product E. No production of a specific antibody of batroxobin was recognized through the experiment.
The kinetic parameters of various kinds of enzyme systems related to a biosynthesis of pregnenolone to androstadienone (Δ16-C19-steroid) in the (neonatal) pig testicular microsomes were determined to discuss its biosynthetic pathway. As a result, the superiority of pathway of pregnenolone→androstadienol→androstadienone (Δ5-pathway) over that of pregnenolone→progesterone→androstadienone (Δ4-pathway) was indicated.
The protective effects of three kinds of typical tannins: gallotannin; tannic acid and gallic acid, ellagitannin; ellagic acid, condensed tannin; bergenin, on ethanol-induced gastric lesions were tested in rats. As the results, ellagic acid and tannic acid showed protective effects. Some related compounds with catechol or its 0-methylate or 0-methyl pyrogallol moiety were tested. However, these compounds did not show statistically significant effects. Since tannins with pyrogallol moiety were effective for ethanol-induced gastric lesions, a mechanism of the protective effects of ellagic acid and tannic acid was examined. Both compounds lost the effects in indomethacin-treated rats. These results suggested that tannins with pyrogallol moiety showed protective effects for ethanol-induced gastric lesions by stimulating the production of prostaglandins in the gastric mucosa.