Physicochemical properties of orotic acid-amine reaction products were examined, and their structure and state in aqueous solution were observed. Since the infrared spectrum of the reaction product exhibited absorptions for carboxyl and amine ions, the product was considered to have a structure in which the amine is bonded to the carboxyl group in orotic acid in an ammonium salt type. Freezing-point depression of the aqueous solution of the reaction product was measured and the reaction product was found to be present in the solution dissociated into orotic acid and ammonium ions. Thermal examination of the aqueous solution system of orotic acid and amines showed that the heat of mixing of orotic acid and amine is equal to the sum of heat of ionization of each component, and this fact endorses the presumed ionic dissociation of the salt.
Solubility of uracil, ethyl orotate, orotic acid and its alkali metal salts, and methyl-orotic acids and their alkali metal salts in water was measured and it was assumed that the small solubility of orotic acid and its alkali metal salts in water was due to the effect of NH and COOH (or COO-) groups in their molecule. Heat of solution of orotic acid salts in water was measured and a correlation was found to exist between the solubility and heat of solution of these salts. Salts of orotic acid, such as its alkali metal salts, with small solubility in water has greater absorption of heat while amine salts of greater solubility shows smaller absorption of heat. Based on these experimental results, considerations were made on the cause for difference in the solubility in water between alkali metal salts and amine salts of orotic acid.
Syntheses of the new sulfonamides, N-(1, 2, 4-oxadiazolyl)-p-substituted benzenesulfonamides, are described. Although the conversion of 5-amino-3-phenyl-1, 2, 4-oxadiazole to the corresponding sulfonamides by the usual techniques was unsuccessful, N1-(3-phenyl-1, 2, 4-oxadiazol-5-yl)sulfanilamide (V) (R=C6H5, X=NH2) was prepared in a low yield by the condensation of sodium of 3-phenyl-5-acetamido-1, 2, 4-oxadiazole and N-acetylsulfanilyl chloride followed by hydrolysis (method 1), and by fusing 5-chloro-3-phenyl-1, 2, 4-oxadiazole and N4-acetylsulfanilamide with potassium carbonate, in a good yield (method 2). V (R=C6H5, X=CH3 and R=C6H5CH2; X=CH3, NHCOCH3) were also prepared by the method 2. Alternatively the isomers of V, N1-(5-R-1, 2, 4-oxadiazol-3-yl)sulfanilamide, were synthesized from N1-hydroxyamidino-N4-acetylsulfanilamide (method 3). The structure of 5-chloro-3-phenyl-1, 2, 4-oxadiazole was discussed from these synthetic evidence.
Besides acetic acid and cinnamic acid, anhydrotaxininol was obtained previously by the hydrolysis of taxinine, desdimethylamino derivative of taxine, an alkaloid contained in Taxes baccata L. and two kinds of substances, alkylanthracene and β-acylalkylnaphthalene, produced with the selenium dehydration reaction from anhydrotaxininol, were obtained, but their structures had not been determined, because of a very minute amount. In order to increase a yield of dehydration product, selenium dehydration reaction was carried out with anhydrotaxininol by the LiAlH4 reduction and alkylanthracene was mainly obtained, without β-acylalkylnaphthalene production. The determination of alkylanthracene structure was attempted synthetically analyzing their ultraviolet and infrared spectra, and, among the alkylanthracene derivatives synthesized, 1, 2, 3, 8-tetramethylanthracene was found to be identical with the dehydration product by melting point depression and infrared spectra. This fact quite agree with the estimated chemical structure of anhydrotaxininol proposed by Uyeo, et al.
In order to determine the structure of alkylanthracene obtained by the Se dehydrogenation reaction from anhydrotoxininol and its LiAlH4 reduced product, syntheses of anthracene derivatives were carried out and some findings in the syntheses as well as ultraviolet and infrared spectra were discussed.
Effect of substituents on the N-oxidation and deoxygenation reactions of β-substituted phenazine compounds was examined because such a substituent does not have steric hindrance on the two nitrogen atoms and only their M effect is thought to affect these reactions. N-Oxidation of phenazine compounds having a substituent with -M effect in the β-position, under a definite, comparatively weak condition, results in the formation of 10-oxides. Deoxygenation of phenazine 5, 10-dioxides possessing a substituent with -M effect in the β-position, under a definite condition, produces 5-oxide. These facts indicate that a substituent with -M effect in the β-position increases electron density of the nitrogen atom in the 10-position of the phenazine ring and that the N-O bond in 5-position is stronger than that in the 10-position in phenazine 5, 10-dioxide.
Condensation of 2-hydrazino-3-phenylquinoxaline with representative ketones to yield ketone hydrazones was investigated. Pyrolysis of the hydrazones yields a 1-substituted s-triazolo[4, 3-a]quinoxaline with concurrent elimination of a hydrocarbon. Factors which apparently govern the elimination of alkyl groups from hydrazones are discussed. The kinetics of the Pyrolysis reaction have been studied and the mechanism for this type of cleavage was presented.
With the following four specimen of tissue portions of blood-vessel from extract of rabbit, pulmonary artery, arcus areae and upper part, lower part of aorta descendens, according to the Magnus method with adrenaline, barium chloride, histamine, serotonin and ACh, the contraction effect was studied from the value of relative activity in the maximum contractive reaction, and its 50% contractive concentration and the slope were obtained, by preparing each dosage-activity curve. The results obtained were: 1) adrenaline showed the strongest effect upon the contraction mechanism of smooth muscle of rabbit blood-vessel, and both serotonine and histamine followed adrenaline. 2) the contraction effect of ACh against blood-vessel was found to be very weak. 3) the contraction effect of barium chloride was found to be strong, however, it needed high concentration. 4) the slope ratio of dosage-activity curve was: 0.7 (aorta descendens)-1.1 (pulmonary artery) with adrenaline, 1.5 with barium chloride, 1.1 with histamine, 0.9 (aorta descendens)-1.1 (pulmonary artery) with serotonine and 1.0 with ACh.
Codensation of cotarnine (I) with o-or p-nitrotoluene derivatives and catalytic reduction of the product afforded 1-aminobenzylhydrocotarnine derivatives. Acylation and alkylation of these derivatives gave 1-acylaminobenzyl-and 1-alkylamino-benzylhydrocotarnine derivatives. By the Grignard reaction of cotarnine hydriodide (XXXV) or by the application of malonic acid to I and subsequent reactions shown in Chart 2, 1-aminoalkylhydrocotarnine derivatives (XXXVI and XXXVIII) were obtained. Hofmann degradation of the methiodides of 1-benzylhydrocotarnine (XXXIX) and its derivative, followed by catalytic reduction of the products afforded N, N-dimethyl-2-phenethyl- (or -p-acetamidophenethyl-) 3-methoxy-4, 5-methylenedioxyphenethylamine (XLII and XLIII).
Cleavage reaction of nuciferine (VII) with metallic sodium in liquid ammonia was carried out and it was found that the methoxyl group in 1-position is liberated to form 2-methoxy-aporphine (VIII) which was identified with the specimen synthesized by another route. The same reaction of nornuciferine (IX) also resulted in the liberation of methoxyl in 1-position to form 2-hydroxyaporphine (X) but another substance (XI) was also obtained at the same time which seemed to have been formed by further progress of the reaction.
New glucuronic acid conjugate was isolated from human urine after sulfisomezole administration, according to the following extraction method. To the urine, was added active charcoal, followed by elution with ammoniacal alkaline solvents, which was absorbed through H-type (A) Dowex 50W-X8, 100-200 mesh, and later extracted with water. Lead acetate precipitates were separated. To the precipitates by basic lead acetate, ammonium sulfate solution and hydrogen sulfide were added to remove lead and then extracted with ammonia after being absorbed through A. The ammonia eluate was evaporated to dryness under reduced pressure and colorless fine crystals, m.p. 170-171° was afforded. According to the synthetic process, potassium salt of N4-carbobenzoxysulfisomezole was condensed with methyl (2, 3, 4-tri-O-acetyl-α-D-glucosylbromid) uronate, and reduced with Pd charcoal. It was hydrolyzed with barium hydroxide, purified by paper partition chromatography and extracted with ammonia after being absorbed through A, and crystals, m.p. 170-171° was obtained. No depression of m.p. by admixture and elementary analysis, ultraviolet and infrared of both compounds extracted and synthesized are in good agreement. Therefore, this compound was identified to be ammonium sulfisomezole-N1-glucosiduronate containing one molecule of water of crystallization.
Examinations were made on the components of Lycopodium serratum THUNB. var. thunbergii MAKINO (Japanese name Hosoba-Togeshiba) from Mt. Hira in Shiga Prefecture. A new triterpene was isolated from the neutral fraction and named serratendiol, C30H48(OH)2, m.p. 300° (diacetate, m.p. 336-338°, [α]D29+18.8°(c=2.34, CHCl3)), with serratenediol monoacetate, C30H48(OH)OCOCH3, m.p. 319-320°, [α]D10-5.7°(c=1.06, CHCl3). New alkaloids were isolated from the basic fraction and named serratinine, m.p. 244-245°, [α]D8-27.8°(c=1.44, EtOH), C12H17(≡N)(=CH-CH3)(-CH2-CO-)(OH)2, serratine, m.p. 253°, C17H27O3N, and serratanine perchlorate, m.p. 239-241°(decomp.), [α]D12-29.3°(c=0.512, EtOH), C11H19O2N⋅HClO4. Known alkaloids, lycodoline (I) and lycodine (II) were also isolated and identified.
A remarkable antipyretic and analgetic action was observed with various C-methyl-7-aminopyrazolo [1, 5-a] pyrimidine derivatives, and thus C-alkyl and C-phenyl substituted 7-aminopyrazolo [1, 5-a] pyrimidine and also 3-bromo derivatives were synthesized. The corresponding 7-aminopyrazolo [1, 5-a] pyrimidine (XIII-XXIV) were prepared from 5-aminopyrazoles by the condensation with β-ketonitriles (I-VIII) in the presence of acidic catalysts. Bromination of XIII-XXIV proceeded to give 3-bromo derivatives (XXV-XXX), only when C-3 was not occupied. On the other hand, bromination of 5-aminopyrazoles gave 4-bromo derivatives (XXXI-XXXIII), which were condensed with pyrimidine to give 7-aminopyrazole [1, 5-a] pyrimidien and it became clear that bromination was taken place at C-3.
It was found that a certain kind of flavone derivatives reacted with Sr2+ to produce yellow, brown to black precipitation in ammoniacal methanol solution, and that the reaction was more sensitive than usual Mg+HCl reaction. In order to investigate the precipitation reaction, six kinds of methylated quercetin derivatives, whose five hydroxyl groups being totally or partially methylated, were studied with Sr2+ for its precipitation formation. The result was that 3, 5, 7, 3′, 4′-pentamethoxyflavone, 5-hydroxy-3, 3′, 4′, 7-tetramethoxyflavone, 3-hydroxy-3′, 4′, 5, 7-tetramethoxyflavone, 3, 4′5, 7-tetrahydroxy-3′-methoxyflavone, were found to be negative with Sr2+. However, 3, 4′, 5, 7-tetrahydroxy-3′-methoxyflavone and 3′, 4′, 5-trihydroxy-3, 7-dimethoxyflavone showed positive reaction. On the reaction products with quercetin and 3, 4′, 5-trihydroxy-3, 7-dimethoxyflavone, the Sr contents were determined quantitatively and the binding molar ratio of flavone derivatives and Sr was found to be 1:1. Therefore, the hydroxyl groups at 3′- and 4′-position of flavone derivatives were considered to participate in the precipitation reaction with Sr2+.
Essential oil of Perilla frutescens BRITTON var. crispa DECCAISNE f. discolor MAKINO contains two principle constituents. One is perilla ketone and the other is a new β-furyl ketone. The latter was separated by rectification and fractional gas chromatography. Through infrared and nuclear magnetic resonance spectra, and ozone oxidation, this substance was found to be isoegomaketone 1-(3-furyl)-4-methyl-2-penten-1-one.
1. A new alkaloid, viroallosecurinine, C13H15O2N, m.p. 136-138°, was isolated from the leaves of Securinega virosa PAX. et HOFFM., and was proved to be enantiomorphous with allosecurinine, with absolute stereochemistry as shown in structure (IV). 2. Another new alkaloid, virosine, C12H15O2N, m.p. 134-135°, was isolated from the roots of the same plant. This molecular formula is to be revised from what was reported in the previous communication. 3. Separatory determination of securinine, its stereoisomeric alkaloid and their dihydroderivatives in plants of the genus Securinega were carried out by means of both chemical separation and gas chromatography. The results are summarized in Tables II and III. The following findings were obtained. i) From the leaves of S. suffruticosa REHD. were obtained securinine (I) as a major alkaloid and allosecurinine (III) as a minor alkaloid, while from the roots allosecurinine (III) in majority and securinine (I) in minority were reversely obtained. ii) From the leaves of S. virosa were obtained virosecurinine (II) dominantly and viroallosecurinine (IV) as a minor quantity. iii) As to the alkaloids of S. suff. REHD. var. amamiensis FURUSAWA, the female plant is similar to S. suff. R., while the male plant contained nearly equal amounts of securinine (I) and virosecurinine (II) as major alkaloids.
It has previously been proved by the authors that the direct bromination of fluorescein by two moles equivalent of bromine, afforded dibromofluorescein, whose 4′ and 5′-position were replaced. Under the similar conditions, the bromination gave, besides 4′, 5′-dibromofluorescein (VI), some sorts of bromofluorescein derivatives, which were observed by paper chromatography with a developing solvent mixture of N-sodium hydroxide solution: 10% Phenol: water (2:1:7). The reaction products were separated, through alumina column chromatography with 2% ammonium hydroxide, into, besides (VI), 2′-bromofluorescein (XIII), 4′-bromofluorescein (XIV), 2′, 7′-dibromofluorescein (V) and eosine (VII), shown in Tables II and III. These bromofluorescein derivatives had been identified with compounds, XII, XIV, V, VI, 2′, 4′-dibromofluorescein (XII) and (VII), synthesized by another process, illustrated in Chart 1.
Thioxolone (I) in each drug preparation was determined quantitatively by polarography. I is decomposed easily into 2, 2′-dithiodiresorcinol (II) in alkaline solution, which showed clear reduction wave on polarogram. I was determined quantitatively, according to the standard addition method by measuring II, produced from the alkali decomposition of I, which was extracted with ethanol from the preparations. No effect was observed by the presence of phenol, resorcinol and bithionol in as much as five times quantity of I, however, a presence of hexachlorophen produced an effect remarkably.
Alkaloids contained in the so-called primitive lotus were examined and components similar to domestic lotus (Nelumbo nucifera GAERTN.), roemerine (I), nuciferine (II), nornuciferine (III), and dl-armepavine (IV), were isolated in crystalline form and identified (cf. Table I).
On the chemical components of Xanthorrhiza apiifolia L'HÉRIT, grown in the south of the United States, as one of the berberine containing drugs, and their pharmacological activities, some remarkable findings were already reported. The cultivation and the yield of berberine·HCl from aqueous extract were examined and comparing with Japanese Phellodendron amurense RUPR. and Coptis japonica MAKINO, the cultivation was found to be easy and also this plant was found to be pretty noticeable plant-resources for berberine·HCl. The base in this plant is also identified with the tetrahydro derivative to be berberine.
Comparison was made between chelatometry and gravimetry for the determination of bismuth in pharmaceuticals. A more simpler, rapid, and accurate determination was found to be as follows: The sample taken as a×10-1g. is dissolved in nitric acid, the solution is diluted with water, and its pH is adjusted to 1-3 with sodium acetate. Bi3+ is titrated with standard solution of 0.05M sodium ethylenediaminetetraacetate, with xylenol orange as the indicator. This method seemed to give better results than by the traditional gravimetry.