It was pointed out that the method which had been used in the past reports to find the synergism between androgen and other compounds was statistically imperfect. The meaning of synergism between two compounds was newly and statistically defined as the interaction term in the design of experiments (this manner of interpretation of interaction is fairly common in the field work of agriculture). According to this definition and the statistical procedure, it could be concluded that the acid fraction in whale testis fat hydrolysate possessed this synergistic activity but the neutral fraction had neither such activity nor androgenic activity significantly enough through SVP and PP weight tests. Moreover, it was found that there was a significant correlation between the weight of SVP and PP which confirmed the result of our previous work, and there was no significant difference between the correlation coefficients in this experiment and in the previous experiments, after comparing them by the statistical method. On the other hand, after analyzing the data of the body weight increase during the injections, there was no significant difference in those effects which were caused by testosterone, the acid fraction and the neutral fraction. It could be found that the equations of first degree could be applied to the curves of growth in the groups TN, TS, S, N, and 1, while the equation of the second degrre could be applied to the curve in the group T...... and the tendency of all curves seemed to be similar to each other. Studies on the chemical analysis of the acid fraction is being continued.
Tsuda and the others previously obtained a hydrocarbon, C54H82, by treating ethereal solution of cholesterol dibromide with bromine. Hefez also obtained the same hydro-carbon from Δ6-isocholestadiene, and Ottke, from cholesteryl acetate, both by the reaction of N-bromosuccinimide. The present workers followed these experiments and confirmed that the hydrocarbon, C54H82, obtained from these three different sources, was an identical substance. The present workers also obtained a very pure hydrocarbon by the reaction of cholesteryl tosylate and N-bromosuccinimide. Although the yield was rather poor, it was found that the same hydrocarbon can also be obtained from isocho-lesteryl methyl ether and N-bromosuccinimide. This hydrocarbon possesses six double bonds and can be represented by a bicholestatriene structure although the bonding position of the two cholestatriene molecules and the position of the double bonds are still undetermined. It was further confirmed that the reaction of Δ6-isocholestadiene and N-bromosuccinimide yielded 7-dehydrocholesterol as well as the hydrocarbon, C54H82, in question.
Crude poisons from globefish ovaries was purified by starch column partition chromatography and by adsorption chromatography using active charcoal. In both cases, amino acids and reducing sugars mixed with crude poison were found to flow at a faster rate than the poison by development. The separation of the poison and amino acids was especially complete in the case of active charcoal. Globefish poison thus obtained showed a potency of 0.6 MLD/g. mouse and when dried, became colorless, and brittle, resin-like solid containing some crystals. This is still not completely pure. The amino acids mixed in the poison were identified by paper chromatography by which it was seen that these amino acids are found in the hydrolysate of the ovary tissues of globefish.
Silver oxide was found to be an excellent reagent in converting some quinolinium alkyl halides into the corresponding quinolones. Some isoquinolinium salts seem to behave in the similar way. Results of any practical importance was not obtained with pyridinium salt.
From the bark of Magnolia salicifolia Maxim., belonging to the Magnoliaceae, two kinds of quaternary bases were isolated. The one was obtained as the chloride, crystallizing in colorless plates or needles, m.p. 260-261° (decomp.), corresponding to the composition of C12H20O2NCl. This base is a new one, and has been named salicifoline chloride. As a result of investigation, this base was proved to be β-(3-hydroxy-4-methoxyphenyl)-ethyl-trimethylammonium chloride (X). The other was isolated as the picrate, crystallizing in yellow needles, m.p. 177-178°, corresponding to the composition of C19H24O3N⋅C6H2O7N3⋅2H2O. This substance was confirmed to be identical with the picrate of magnocurarine (I), an alkaloid of Magnolia obovata Thunb.
The authors isolated palmatine as an alkaloid, and parabaenin as a nitrogen-free substance from Parabaena hirsuta (Becc) Diels, (Fam. Menispermaceae). Parabaenin is colorless needle crystals, m.p. 181.5° (decomp.), and its formula coincides with C20H22O6. This substance indicates the same melting point as columbin, a bitter substance of the columbo root, but the analytical data, etc. are different. Parabaenin absorbs 4 moles or hydrogen by catalytic reduction with Pd-charcoal, and yields a hydrogenated compound. Also, by hydrolysis, parabaenin gives an acid. Therefore, parabaenin is assumed to be a terpenoid compound having similarities to columbin.
The authors carried out the decomposition reactions of diphenylene dioxide, 3, 7-dimethyldiphenylene dioxide, phenoxthine, and several similar compounds by metallic sodium in liquid ammonia. As a result, the following new knowledge has been obtained: 1) When isotetrandrine, tetrandrine and cycleanine are reacted by metallic sodium in liquid ammonia, these are bisected into two coclaurine type molecules and when this mode of decomposition is compared with the fundamental experimental results obtained this time, both decomposition processes are found to proceed exactly in the same way. 2) Furthermore, diphenyl ether derivatives, having a phenolic hydroxyl group, show great resistance to cleavage reaction, and, if these substances are made to react forcibly, the cleavage products become resinous. Consequently, it was confirmed that berbamine and other phenolic bases cannot be bisected into two coclaurine type molecules by the cleavage of the two ethereal oxygen linkages in one step.
By the application of a cleavage reaction to isotetrandrine, the authors ascertained that in the bisection of biscoclaurine alkaloids by metallic sodium in liquid ammonia, the same reaction likewise progresses, when metallic potassium is used in place of metallic sodium.
When O-methyloxyacanthine is reacted by metallic sodium in liquid ammonia, d-1-(4'-hydroxybenzyl)-6, 7-dimethoxy-N-methyl-1, 2, 3, 4-tetrahydroisoquinoline (d-armepav-ine) (IV) is obtained in an yield of about 50% of the bisected phenolic base. As a result of this, it has been recognized that the cleavage proceeds under the type shown in formula (III), and has proved directly that the structure of oxyacanthine is as represented by formula (I).
As a result of search for the other bisected base, which is obtained besides d-armepavine (III) when O-methyloxyacanthine (II) was reacted with metallic sodium in liquid ammonia, the l-type bisected base was obtained, contrary to anticipation. It is considered to have been formed by the Walden inversion taking place during the reaction.
Previously it was presumed by this group that biscoclaurine alkaloids, possessing phenolic hydroxyl group, could not be bisected into two coclaurine type molecules by one-step cleavage rcaction on their oxygen linkages; and that, first of all, only one of the two ethereal oxygen linkages, combining both isoquinoline nuclei, would be cleaved. The author has succeeded in bisecting berbamine into two coclaurine-type molecules by a two-stage cleavage reaction. The intermediate product, which was obtained by the first stage cleavage reaction, was methylated, and then the second stage cleavage reaction was carried out. On the basis of these results, the chemical constitution of berbamine has finally been determined.
Aus Pirola japonica Sieb. wurde ein neues diuretisches Glukosid isoliert, das Pirolatin genannt wurde. Auf Grund der Ultraviolett-Absorptionskurve und wegen seiner anderen verschiedenen Eigenschaften ist wohl anzunehmen, dass das Pirolatin ein phenol isches Glukosid darstellt. Pirolatin lieferte bei Methylierung Methylpirolatin und wurde katalytisch zu einem Tetrahydrokörper hydriert, welcher sich durch Hydrolyse in d-Glucose und Tetrahydro-pirolagenin spaltete und ausserdem durch Acetylierung Pentaacetyltetrahydropirolatin ergab. Aus dem Tetrahydropirolagenin gewann man durch Acetylierung Diacetyltetrahydro-pirolagenin, welches, hydrolysiert, das ursprüngliche Tetrahydropirolagenin regenerierte. In Anbetracht dieser Derivate wurde für das Pirolatin die Summenformel C23H34O7⋅H2O auf gestellt.
Durch Oxydation von Methylpirolatin wurde eine Phenolcarbonsäure erhalten, welche Pirolatinsäure genannt wurde. Diese gab durch Entmethylierung Norpirolatinsäure und durch Decarboxylierung p-Oxy-o-kresolmethyläther, dessen p-Nitrobenzoat mit dem synthetisch hergestellten Präparat gemischt keine Depression zeigte und als dasselbe identifiziert wurde. Von den drei für Norpirolatinsäure möglichen Konstitutionen wurden 2, 5-Dioxy-3-methyl- sowie 2, 5-Dioxy-4-methylbenzoesäure hergestellt und mit Norpirolatinsäure unmittelbar verglichen. Dabei wurde festgestellt, dass es sich bei ihnen um andere Säuren als die Norpirolatinsäure handelt. Als Schlussresultat ergab sich somit, dass die Norpirolatinsäure die 2, 5-Dioxy-6-methylbenzoesäure und die Pirolatinsäure die 2-Oxy-5-methoxy-6-methylbenzoesäure sein dürften. Dementsprechend wurde eine vorläufige Konstitutionsformel für Pirolatin in Vorschiag gebracht.
The pH 5, 4-precipitate extracted from bovine parotic gland and possessing the action of lowering the calcium level in rabbit serum was subjected to fractional precipitation with sodium sulfate. The fraction possessing the most potent action was extracted with physiological saline solution by which a preparation was obtained possessing ten times the strength of the crude material. The total potency of various fractions obtained by fractionation was about 80% of the total potency of the crude material. Moisttire content of various preparations were estimated at the time of potency tests by which it was shown that the potency was greatly decreased when the drying process of the preparation was poor. The moisture content of the preparation must be below 7%, the most ideal being around 5%. By the extraction with saline solution of acetone. dried pH 5.4-precipite, a certain amount of increase in potency was effected.
When the pH 5.4-precipitate is purified by means of fractional precipitation with ammonium sulfate, an effective protein substance is obtained in crystalline state from the fraction precipitating at 12.1% concentration of ammonium sulfate. This substance was found to be approximately 90% pure by electrophoretic analysis. Its behavior towards sodium and ammonium sulfate is similar to that of γ-globulin but its mobility in electrophoresis give values intermediate of albumin and α-globulin of human serum, and much nearer that of α-globulin. The dialyzate of the crystals, when injected intravenously to rabbit at the rate of 1mg. per 2kg. body weight (calculated from evaporation residue), showed the decrease of 14.41% rate in serum calcium. Fractional precipitation with sodium sulfate alone gave amorphous precipitate but subsequent fractional precipitation with ammonium sulfate gave crystalline product. The fraction of total ammonium sulfate-saturation, compared to the crystalline portion, showed weak potency with strong toxicity. This toxicity could not be removed by dialysis.
A simplified isoquinoline synthesis is described. In this method one mole each of appropriately substituted β-phenethylamine and acid were mixed under toluene and the mixture was boiled with an excess of phosphoryl chloride, giving isoquinoline in a fair yield. The isolation of the intermediate acid amide in the usual Bischler-Napieralski Perkin method was thus made unnecessary.
On dry-distillation of d-diacetyldihydro-usnic acid by itself, 7-acetyl-3, 5-dimethyl-4-acetoxy-6-hydroxycoumaran-2-one was obtained with acetyl acetone, whereas, in the presence of anhydrous CaCl2, 7-acetyl-3, 5-dimetyl-6-hydroxycoumaran-2-one was formed.
(1) Sodium 3-phenylazonaphthionate and its derivatives were synthesized by diazotized aniline and its ring-substitute and coupling the resulting diazonium compounds with sodium naphthionate. (2) These compounds were tested as to their activities iv vitro against Encephalitis japonica. (3) Sodium 3-phenylazonaphthionate possessed the strongest activity against the virus and the lowest toxity among the series of 3-phenyl-azonaphthionates.
(1) Sodium 3-phenylazonaphthionate shows a remarkable. effect on the Japanese encephalitis virus in vitro and in vivo. The compound possesse virucidal, protective and curative effects against neurotropic virus and a low toxity. (2) It is assumed that the antiviral activity of sodium 3-phenylazonaphthionate might be caused by direct interaction of the compound and the virus. (3) Sodium 3-phenylazonaphthionate is of promise for treatments of diseases caused by small neurotropic viruses.
Saccharine was found to be a suitable starting material for the preparation of alkyl and aralkyl secondary amines, according to the schema shown on page 211 (I-VI). It is not necessary to isolate intermediate III, IV and V. The readiness of the last-stage hydrolysis (V-VI), when compared with that of usual arylsulfone dialkylamide is to be emphasised. Ten kinds of both alkyl- and aralkyl-amines were prepared. It was proposed to call this “Saccharine method.”
Die Konstitution des Disubstitutionsproduktes bei der Nitrierung bzw. Bromierung des 4-Oxypyridin-N-oxydes wurde als 3, 5-Derivat festgestellt, dass die elektrophile Substitution des 4-Oxypyridin-N-oxydes ausschliesslich von der C4-Hydroxyl-Gruppe dirigiert und der Substituent nach ihrer ortho-Stellung gelenkt wird.
Au moyen de l'analyse spectroscopique aux rayons X, la détermination de néodyme déposé dans les viscères a été recherchée. La quantité infime de néodyme existant dans l'organisme est extraitée par précipitations provoquées par Ce(SO4)2, FeCl3 et CaCl2, respectivement. Cette extraction est nécessaire pour procéder à l'analyse spéctroscopique aux rayons X de néodyme.
O-Methylsalicifoline iodide (II) derived from salicifoline chloride, an alkaloid of Magnolia salicifolia Maxim., was synthesized from homoveratrylamine. Thus, the structure of salicifoline chloride has synthetically been confirmed to be represented by (I).