A new bitter secoiridoid glucoside, centapicrin, C25H28O12, mp 234-237°, has been isolated from the herb of Erythraea centaurium [Linne] PERSOON (Gentianaceae), together with two known glucosides, swertiamarin and sweroside. The structure of centapicrin (I) was established is 2'-(m-hydroxy) benzoyl-3'-acetylsweroside from spectral and chemical evidence.
General pharmacological actions of 2-(benzylidenehydrazino)4-tert-butyl-6-piperazino-s-triazine (TR-35) were examined. TR-35 showed a moderate sedative, muscle-relaxant, and anti-convulsant actions in mice and these effects were more potent than those of meprobamate. Basic anti-inflammatory agents such as mepyrizole or diphenamisol also showed these properties, Although TR-35 expressed taming effects in mice and rats, it had no depressant action against conditioned avoidance response and methamphetamine-induced hypermotility. As for autonomic nervous system or smooth muscle, TR-35 seemed to have a weak ganglion blocking and faint smooth muscle directing actions. Little effect was also observed on blood pressure of urethane anaesthetized rat.
Cyclization of 2-amino-3-hydrazinoisocarbostyril (I) and its derivatives (IIa-d and IIIa-f) was studied. The reaction of I with N, N-dimethylformamide dimethyl acetal gave 1-(N, N-dimethylaminomethyleneamino)-s-triazolo[1, 5-b]isoquinolin-5(1H)-one (IVa), and with formamidine acetate, 1-aminotriazoloisoquinolinone (IVb), which was produced by the reaction of IIc with N, N-dimethylformamide diethyl acetal. The reaction of IIa with the same reagent afforded 1-benzylideneamino derivative (IVd), but no cyclization products were obtained from IIb and IId, and their reactions resulted in 2-(N, N-dimethylaminomethyleneamino)isocarbostyrils (Vb and Vd). 1, 2-Dihydro-6H-s-tetrazino[2, 3-b]isoquinolin-6-ones (VIa-e) were produced by the cyclization of IIIa to IIIe with N, N-dimethylformamide diethyl acetal. VIa and VIb can also be obtained by the reaction of I with acetic anhydride or propionic anhydride in ethyl orthoformate. 1-Methyl-2-acyltetrazinoisoquinolinone derivatives (VIIIa, VIIIb, VIIId, and VIIIe), which were prepared by the methylation of VIa to VIe with dimethyl sulfate or methyl iodide, were converted into 1-methylaminotriazoloisoquinolinones (IXa-c) under alkaline conditions, as a result or deacylation ana ring contraction.
YAU-17, a new local anesthetic, blocked the neuromuscular transmission in isolated frog sartorius muscle at a dose of 3×10-5M which prevented neither the directly elicited twitch of the muscle nor the conduction of action potential in isolated frog sciatic nerve trunk, indicating the site of action to be the neuromuscular junction. The blockade produced by YAU-17 was antagonized by guanidine, without being affected by neostigmine and potassium ion in the sartorius muscle preparations. Thus, the properties of YAU-17 in blocking neuromuscular transmission were similar to those of procaine and lidocaine, but not to those of d-tubocurarine whose neuromuscular blockade was antagonized by neostigmine and potassium ion. All of the drugs tested (YAU-17, procaine, lidocaine, and d-tubocurarine) inhibited the acetylcholine-induced contracture in the isolated frog rectus abdominis muscle. Although YAU-17, procaine, and lidocaine caused neuromuscular blockade in isolated frog sartorius muscle, these drugs in doses up to 30 mg/kg, i.v., given to rats anesthetized with pentobarbital had practically no effect on indirectly elicited contraction of gastrocnemius muscle. This held also true for cocaine and dibucaine, whereas d-tubocurarine consistently exhibited muscle relaxing action in both preparations. These results indicate that the effects of YAU-17 on neuromuscular transmission were similar to those of local anesthetics, procaine and lidocaine, but not to those of d-tubocurarine.
The electrode reaction of vitamin K5 (4-amino-2-methyl-1-naphthol hydrochloride) on a mercury electrode was studied by polarography in aqueous and alcoholic solutions. Vitamin K5 shows two well-defined anodic waves on a direct current (DC) polarogram obtained from both aqueous and acidic ethanol solutions. One of them is due to the oxidation of 4-amino-2-methyl-1-naphthol (I) and its limiting current was found to be proportional to the vitamin K5 concentration, and the other corresponds to the formation of mercurous chloride on the electrode surface. Electro-oxidation of I also gives rise to a distinct peak on an alternating current (AC) polarogram obtained from aqueous solution, whose height is proportional to the amount of vitamin K5 in a very low concentration range. Such experimental results have been confirmed to be advantageously applicable to the microdetermination of vitamin K5. The AC polarographic method can be applied to determine a minute quantity of vitamin K5 as low as 0.1 ppm range. The simultaneous determination of vitamin K5 and other vitamin K's can be made by the measurement of DC polarogram in acidic ethanol solution with satisfactory results.
5-Amino-1(2H)-phthalazinone (5) was synthesized by the reaction or 3-hydroxy-4-nitrophthalimidine (1) or phthalide (2), and various derivatives (1-acetoxy-5-acetylamino-phthalazine, 5-acetylamino-1(2H)-phthalazinone, 5-acetylamino-1-hydrazinophthalazine, and 5-amino-1-hydrazinophthalazine) of 5 were prepared.
The reaction 4-aminoquinoline 1-oxide (4-AQO) or 4-hydroxyaminoquinoline 1-oxide (4-HAQO) with POCl3, and its mechanism were examined, and it was found that the reaction of 4-AQO, 4-HAQO, or their derivatives with POCl3 afforded the corresponding 3-chloro compound as the main product. A reaction mechanism was proposed for the formation of the 3-chloro compound from 4-AQO and 4-HAQO.
Examinations were made on the action of anhydromevalonic acid lactone, which inhibits incorporation of mevalonic acid into cholesterol in the cell-free system of rat liver, on microorganisms was studied. Microorganisms examined were mevalonic acid-requiring Lactobacillus acidphilus ATCC 4963 and L. heterohiochii H-1, and Saccharomyces cerevisiae and S. carlsbergensis ATCC 9080 which do not require mevalonic acid and have the ability to synthesize sterol. In the presence of 0.1 μg/ml of mevalonic acid, L. acidophilus required ca. 15 mg/ml of anhydromevalonic acid lactone for 50% suppression and 25 mg/ml for 100% suppression. In the presence of 1.0 or 4.0 μg/ml of mevalonic acid, L. heterohiochii required 0.5 and 20 mg/ml, respectively, of anhydromevalonic acid lactone. In the presence of 15 and 20 mg/ml of anhydromevalonic acid lactone the growth of S. cerevisiae and S. carlsbergensis was completely inhibited. However, there was hardly any effect on the sterol content per unit cell weight.
Excretion rate constants of salicylic acid, benzoic acid, phenol, and phenobarbital from goldfish under various conditions, i.e., high and low drug concentration in outer solution, with or without urea, were compared. Since excretion rate obtained from absorption experiment with a high drug concentration of an outer solution was larger than that from excretion experiment in lower drug concentration, the drug in the outer solution might promote the excretion. Addition of urea in outer solution also promoted the excretion and this effect was also larger in the absorption experiment than in the excretion experiment.
In order to find the optimal medium composition for the induction and production of uricase by the F1 strain, a fungus isolated from the feces of a Japanese nightingale (Cettia diphone), effect of nitrogen source was examined. Twenty-two kinds of amino acid were examined in a medium containing Casamino acid. Then, serine, aspartic acid, glycine, glutamic acid, proline, and asparagine, found to be most effective for the mold growth and uricase production, were examined for uricase production in a medium not sontaining Casamino acid. Preliminary experiments had shown that Casamino acid is the most suitable nitrogen source for the growth of F1 strain and none of the amino acids tested was found to be more effective than Casamino acid for speciftc uricase production, although serine showed about the same effect as Casamino acid. While asparagine accelerated the growth of this fungus, it acted inhibitory for the enzyme production and this was found to be due to the marked inhibition of the incorporation of urate by the fungus in the asparagine medium. It was proved that the effect of Casamino acid for fungal growth and enzyme production was the consorted action of componental amino acids and that its optimal concentration was about 1.0%. The characteristic of Casamino acid was found to be a more efficient production of the enzyme than single amino acid and this was due to the marked effect of Casamino acid in shortening the induction period of growth.
DC conductivity of a mixture of cholesterol and cholesteryl propionate was measured and compared with dielectric loss data at 1 K cps frequency. Current density-electric strength behavior was measured on the mixture in the solid, liquid crystal and isotropic liquid states to characterize conduction in cholesteric liquid crystal. Ohm's law was observed for both liquid crystal and isotropic liquid phases. Activation energies of dielectric conductivity and DC conductivity agreed well on these mixtures.
Molecular weight, M, of fractionated poly (vinylpyrrolidone)(PVP) was determined by the light scattering method at 436 nm. The relationship between M and intrinsic viscosity, [η], measured at 25°, was found to be [η]=5.75×10-4M0.60(105≤M≤106) and [η]=0.134M0.19 (106≤M≤107). It was suggested that the reason why the power for M becomes smaller when the M is higher than 106 is that there occurs a branching on PVP molecule with a high degree polymerization. The dimension of PVP coil calculated from the intrinsic viscosity and the radius of gyration is about three times the dimension of it ideal Gaussian coil assuming the bond angle of hydrocarbon chain. It was concluded from the relationship between [η] and M of PVP and poly (vinyl alcohol)(PVA) that the size of polymer coil of PVP and PVA is almost the same when the degree of polymerization of both polymers is in the range of 800 to 4000. It was found that the second virial coefficient, A2, of PVP is proportional to M-0.307.
Treatment of the 2-oxo-5α-stereoids with potassium t-butoxide and oxygen in tbutanol gave 2, 3-diketones and not 1, 2-diketones as the reaction product, and also produced Δ2-semidiones but not the Δ1-semidiones in the ESR measurement. The substituent effect of the oxo group on the C-11 position of 25D, 5α-spirostan-2-one was not observed in the product analysis, but the ESR pattern of the Δ2-semidione was different from that of the nonsubstituted one. 25D, 5β-Spirostan-2-one afforded the 2, 3-diketone as a major product and the 1, 2-diketone as a by-product under the same reaction conditions, but the principal product obtained from 25D, 5β-spirostan-2, 11-dione was the peroxide (XXa) which was confirmed to be a novel transannular type compound by various ways.
Determination of 22 amino acids, including asparagine and glutamine, in serum by gas liquid chromatography (GLC) of N-isobutyloxycarbonyl (N-isoBOC) methyl ester derivatives was carried out. Serum samples were deproteinized with picric acid and purified with a cation-exchange resin. Amino acids thus obtained were derived to theif N-isoBOC methyl esters and analyzed by GLC. Recoveries of amino acids added to sera ranged 93.1-100.5% ; an exception was tyrosine which gave 70.3%. The data obtained by GLC method were in good agreement with those by the automated amino acid ana1yzer.
The reaction of ethylenediamine (ED) and propylene glycol was examined in the alumina-packed bed reactor. Methylpiperazine (MP) was obtained with other products (methylpyrazine, methylethylpyrazine, methylpropylpyrazine). Since this reaction mechanism is unknown, statistical method was used to find optimum conditions for the yield of methylpiperazine. The first part of the investigation consisted of central composite design. Five variables were chosen ; reaction temperature (a), catalyst weight (b), molar ratio of reactants (c), amount of water added (d), and percentage of added promotor (e). The second-order response functions were given for (1) yield of MP, (2) total yield, and (3) MP selectivity. In analysis of variance for (1) and (2), the fits of functions were reasonable. Experiments in the direction of the steepest ascent based on the second-order response function showed that the yield of MP dropped beyond 313°. It was concluded from the experimental results that the optimum conditions are as follows : (a) 312.9°, (b) 24.71 g, (c) 0.4/1.0 (ED ml/PG ml), (d) 0.853/1.0 (H2O ml/PGI ml), and (e) 7.073%, by which the maximum yield was 45.27%.
Cholesteryl nonanoate takes the left-handed cholesteric liquid crystalline state, cholesteryl chloride takes the right-handed cholesteric liquid crystalline state, and their mixture takes a compensated nematic liquid crystalline state in a limited range of composition (60-70 mol% of cholesteryl chloride). The dielectric properties of this mixture were examined and the die1ectric dispersion is due to Cole-Cole dispersion at a high frequency and to m's law at the low frequency on the mixture. Absolute theory of rate process was applied to the relaxation frequency estimated from the Cole-Cole dispersion, and activation free energy, enthalpy, and entropy of the dipole rotation were calculated.
Acyclic isoprenoid hydrocarbons in NTU shale oil distillate, boiling from 280° to 305°, were isolated through thiourea adduct formation. The major constituents were determined to be 2, 6, 10-trimethylpentadecane, 2, 6, 10, 14-tetramethylpentadecane, 2, 6, 10, 14-tetramethylhexadecane, and 2, 6, 10, 14-tetramethyl-1-pentadecene. The meaning of the present result was discussed from the point of the origin of shale oil and its use as a chemical raw material.
The conversion of trimethylenediamine on platinum group metal -Al2O3 catalysts was examined in a stream of water vapor and hydrogen gas. The reaction was carried out over the temperature range of 220° to 410°, at atmospheric pressure. 2-Ethylpyrimidine (P3) and 2-methylpyrimidine (P2) were obtained as the principal products. Rh-Al2O3 and Pt-Rh-Al2O3 catalysts gave the best yield of P3, which was about 50% at the reaction temperature between 330° and 350°. H2O vapor and H2 gas showed a suppressive effect on the cracking and catalyst decay. It was concluded from kinetic studies that the formation of P3 from trimethylenediamine involved the following successive reactions : disproportionation of trimethylenediamine to 3, 3'-diaminodipropylamine and ammonia (reaction 1), deaminocyclization of 3, 3'-diaminodipropylamine to 2-ethylhexahydropyrimidine (reaction 2), dehydrogenation to 2-ethyl-1, 4, 5, 6-tetrahydropyrimidine (reaction 3), and finally dehydrogenation to P3 (reaction 4). N-Propionyltrimethylenediamine was present in equilibrium with 2-ethy1-1, 4, 5, 6-tetrahydropyrimidine. It was concluded that reactions 1 and 4 were ratedetermining steps, and that reactions 2 and 3 were very rapid. The rate of formation of P3 was determined and the predicted values agreed well with the experimental results. It was considered that P2 was formed from 2-methylhexahydropyrimidine produced by demethylaminocyclization of 3, 3'-diaminodipropylamine.
The main Porter-Silber reaction products of Betamethasone (I) was 11β, 21-dihydroxy-9α-fluoro-16β-methyl-1, 4-pregnadiene-3, 20-dione (V), and 21-phenylhydrazone (III) of I was not found as the reaction product. On the contrary, the main product from Dexamethasone (II) was 21-phenylhydrazone (IV) of II. The reaction mixture of I, V, and II with PS reagent showed absorption maxima at 450, 450, and 423 nm, respectively. It was found that the chromophore showing an absorption maximum at 450 nm was derived from I or V by the reaction with sulfuric acid.
Possibility for the determination of amino acids in hydrolysates of bovine albumin, α-chymotrypsin, casein, and insulin by a gas chromatographic method using their Nisobutyloxycarbonyl methyl ester derivatives was demonstrated. The data obtained were in good agreement with those by the automated amino acid analyzer.