By the condensation of anisaldehyde and carbon disulfide with aminoacetonitrile in ethyl acetate, 5-p-methoxybenzylideneaminothiazolo-2-thiol was obtained. Application of alkyl halides, allyl bromide, benzyl chloride, β-hydroxy (methoxy, ethoxy, butoxy) ethyl halide, or phenacyl bromide, on the sodium salt of 5-(p-methoxy, o-hydroxy, p-dimethylamino) benzylideneaminothiazolo-2-thiols yielded the corresponding 2-alkyl (allyl or aryl) thin derivatives. Application of ethylene bromide to the sodium salt of 5-p-hydroxybenzylideneaminothiazolo-2-thiol (III) yielded 1, 2-bis (5-o-hydroxybenzylideneamino-2-thiothiazolyl) ethane. By the acetylation of (III) with hot acetic anhydride, the diacetate was obtained; By the acetylation of 5-p-hydroxybenzylideneamino-2-β- hydroxyethylthiothiazole (XXVI) with cold acetic anhydride, the monoacetate and with hot acetic anhydride, the diacetate were obtained.
p-Dimethylaminobenzaldehyde, which had earlier been used for the measurement of blood level of p-acetylaminobenzaldehyde thiosemicarbazone (thioacetazone), was utilized for measuring its concentration in the urine and a sensitive method for determining thioacetazone alone, removing any interfering material contained in the urine, was devised. The value obtained by this method is that of thioacetazone alone, excluding majority of the biological decomposition products of thioacetazone. By the combination of the present method and the diazotization method to measure the amount excreted, the difference of the two values gives the rate of biological decomposition of thioacetazone and the values so obtained showed that 100mg of its powder taken orally resulted in an average of about 40% decomposition and excretion. Enteric-coated tablets were also found to be decomposed to a fair extent. Application of this method in the presence of INAH, PAS, or streptomycin resulted in complete removal of INAH. The effect of 2% solution of PAS on the present method was below approx. 0.2mg% calculated as thioacetazone.
Separation was attempted of several compounds assumed to be the biological decomposition products of p-acetylaminobenzaldehyde thiosemicarbazone (thioacetazone) by paper chromatography with butanol as a solvent. The separation of thioacetazone, p-aminobenzaldehyde thiosemicarbazone, and semicarbazone was not sufficient. By spraying 10% copper sulfate solution over an area about 7cm. wide from the original spot toward the direction of development, drying in air, and developing the foregoing mixture, both the thiosemicarbazones remained in the original spot while the semicarbazone alone moved upward, giving a characteristic spot. Therefore, biological decomposition products of thioacetazone in the urine were examined by paper chromatography with butanol as a solvent and spraying copper sulfate solution. It was found that when thioacetazone powder is administered orally, p-acetylaminobenzoic acid, p-aminobenzoic acid, and glucuronic acid thiosemicarbazone are detected in the urine, while the administration of enteric-coated tablets resulted in the detection of p-aminobenzaldehyde thiosemicarbazone in the urine, which was not found when the powder was administered, indicating that thioacetazone is deacetylated when absorbed through the intestines.
Decomposition of p-acetylaminobenzaldehyde thiosemicarbazone (thioacetazone) in the digestive tract was examined by paper chromatography. Thioacetazone is decomposed into p-acetylaminobenzaldehyde and thiosemicarbazode in artificial gastric juice and is also deacetylated to form p-aminobenzaldehyde thiosemicarbazone. Its decomposition in the intestines was examined with artificial enteric juice, duodenal mucous enzyme from a rabbit and bovine, and intestinal flora (Escherichia coli communior, Streptococcus faecalis, and Lactobacillus acidophilus). No change occurred in artificial enteric juice and Escherichia coli, but thioacetazone was deacetylated by intestinal mucous enzyme, Strept. faecalis, and Lact. acidophilus. p-Acetylaminobenzaldehyde was also found to be deacetylated by the Lactobacilli.
Deacetylation rate of thioacetazone by the washed-cell suspension of Streptococcus faecalis R at each pH between pH 4 and 9 was examined and it was found that the deacetylation was the most active at around pH 7.4. The buffers used in these experiments were Clark-Lubs buffer of pH 4-7 and pH 8-9 and phosphate buffer of pH 7.4. Periodical determination of the deacetylation rate of thioacetazone with washed-cell suspension prepared with phosphate buffer of pH 7.4 showed that deacetylation was practically completed in about 40 hours. The amount of dried cells was 10mg./cc. and the concentration of thioacetazone, 68γ/cc. Addition of glucose to 1% ratio in this washed-cell suspension of pH 7.4 resulted in virtual cessation of deacetylation after about 3 hours and the rate of deacetylation effected was also small. The pH of the sample solution tended to become acidic with passage of time, the pH becoming about 4 after 24 hours.
It was surmised from the preceding work that lactobacilli preparations would also effect deacetylation of thioacetazone. Therefore, deacetylation of thioacetazone was examined with commercial preparation, “Lactomin powder, ” and it was found that the rate of deacetylation was very slight, as shown in Figs. 1 and 2. However, taking of “Lactomin powder” would effect increase of lactobacilli in the intestines and the deacetylation of thioacetazone would probably increase, which suggests that these two drugs should not be used together. Examination of the concurrent use of diastase and medicinal yeast with thioacetazone was also examined but these were found not to affect thioacetazone.
Change of thioacetazone in the liver was examined by the perfusion method through surviving rabbit liver and it was found that thioacetazone is decomposed into p-acetylaminobenzaldehyde and thiosemicarbazide (Fig. 1), that the former is further oxidized to the acid, and that the latter is excreted through conjugation with glucuronic acid. The excretion of glucuronic acid during oral administration of thioacetazone was found to be clearly larger than that during normal times (Fig. 2), and the amount of glucuronic acid in the perfusion solution in the liver perfusion experiments was also larger when compared to the control (Fig. 3). Glucuronic acid thiosemicarbazone was detected by paper chromatography, p-Aminobenzaldehyde thiosemicarbazone was found to be well acetylated by rabbit liver (Fig. 4) so that the deacetylation product of thioacetazone in the gastrointestinal system is again acetylated in the body. It seemed that the detoxication of thioacetazone by conjugation with ethereal sulfuric acid does not generally take place.
Coixol was synthesized starting with 5-methoxy-2-aminophenol or its hydrochloride by (1) pyrolysis of its phenylurea derivative, (2) pyrolysis of its phenylurethan derivative, (3) application of phosgene, or by (4) preparation of 6-methoxy-2-thio-benzoxazole (colorless needles, m. p. 173.5-174°), from it to 6-methoxy-2-chloro-benzoxazole (colorless needles, m.p. 63-65°), and hydrolysis of the latter. Isomers of coixol with a methoxyl in the different position and a few of its derivatives were prepared by fusion of the corresponding aminophenol hydrochloride with urea. 4-Methoxybenzoxazolone, colorless needles, m.p. 194-195° (acetate, m.p. 122-124°; benzoate, m. p. 142°; ethoxycarbonyl derivative, m.p. 60°); 5-Methoxybenzoxazolone, colorless needles, m. p. 169-170° (acetate, m.p. 101-102°; benzoate, m.p. 135°; ethoxycarbonyl derivative, m.p. 82-83°); 7-methoxybenzoxazolone, colorless needles, m.p. 148-150° (acetate, m.p. 119-122°; benzoate, m.p. 187-188°; ethoxycarbonyl derivative, m.p. 114-115.5°). These benzoxazolones exhibited an absorption of strong intensity at around 5.65μ due to C=C stretching vibration.
The essential oil of Artemisia capillaris THUNB., which was found to have a powerful growth inhibition and bateriocidal action on dermatophytes, was found to show toxicity, LD50, of 0.24±0.019cc./kg. by intraperitoneal injection in mice. Physicochemical stability of its ointment and periodical change of ointment potency were examined. The ointment showed good results in experimental trichophytia in guinea pigs, and it was confirmed that no recurrence of trichophytia was evident a few days after cessation of treatment.
Since the azlactones of α-acylaminocinnamic acids are easily available, synthesis of 1-substituted isoquinolines from these azlactones through α-acylcinnamic acid, β-acylaminostyrene, and acyl-β-phenethylamide was examined. It was thereby found that 1-phenyl and 1-(3, 4-dimethoxyphenyl)-6, 7-dimethoxy isoquinolines could be prepared by this route and a new compound, 1-(3, 4-dimethoxyphenyl) isoquinoline, was synthesized. However, attempt to prepare 3-substituted norharmanes from α-acylamino-β-indolylacrylic acids failed.
Alkaloids were titrated in glacial acetic acid by the high frequency method and a new, simple titrator was devised for it, giving good results. The limit of the strength of bases that could be titrated was the dissociation constant of about 10-10 in aqueous solution. Results of this high frequency titration were approximately the same as those obtained by potentiometric or indicator methods.
Interference of malic oxidation of coil bacilli by nitrofurans (Furacin, Z-Furan, Guanofuracin) is not recovered by the addition of cystein or glutathione. Bacterial -SH group was determined after application of Guanofuracin to the bacterial suspension but its decrease was not detected. The absorption of inorganic phosphoric acid from the medium accompanying malic and succinic acid oxidation is detected on application of Furacin and Z-Furan but is almost entirely obstructed by Guanofuracin.
Washed-cell suspension of Escherichia coli shows a marked inhibition of respiration when preincubated with 5×10-4M of 2-(5-nitro) furfural semicarbazone (Furacin), but addition of the same concentration of Furacin at a period when substrate oxidation is occurring does not show any inhibition of respiration. The effect of Furacin is not reversed by the washing or dialysis of bacteria or addition of glutathione and the nitro group of Furacin disappears or is reduced by the application of sufficiently washed cell suspension of bacteria.
Oxidation of pyruvic, oxalacetic, and acetic acids by the live bacterial suspension of Escherichia coli is not inhibited under the conditions by which malic acid oxidation is partially (25%) inhibited. Even under the same conditions, preincubation of the bacterial suspension with Furacin to effect complete inhibition of malic acid oxidation results in the inhibition of the oxidation of pyruvic, oxalacetic, and acetic acids. However, oxidation of succinic and formic acids, even after such preincubation, showed the absorption of oxygen corresponding to 1 atom of oxygen per mole of substrate, indicating that the one-step reaction of succinic to fumaric acid and formic acid to carbon dioxide still remains. The concentration for 50% inhibition, I50, of nitrofurans against malic oxidation by bacterial suspension were: 2-(5-nitro) furfural semicarbazone 10-4M; 5-nitrofurylacrylamide, 3×10-5M; 5-nitrofurfural aminoguanidine, 3×10-5M. The succinic oxidase obtained by extraction after exposure of E. coli to supersonic waves was not inhibited by 5×10-4M of 5-nitrofurfural semicarbazone.
Colt bacilli were destroyed by irradiation of supersonic waves and succinic oxidase was extracted. It was found that irradiation of 560Kc., 1800V., and 0.29-0.30A, for 15 minutes resulted in almost complete extraction of succinic oxidase in cellfree state. When the coli bacilli are destroyed under above conditions and centrifuged at 10, 000r.p.m., succinic oxidase activity is detected in the microsomes of 20-50mμ. The succinic oxidase so extracted is precipitated in the majority by 60-70% saturation of ammonium sulfate.
Periodic acid oxidation was attempted with monohaloanilines, aminophenol, anisidine, phenetidine, phenylenediamine, aminoacetanilide, aminobenzaldehyde and its oxime and phenylhydrazone, aminoacetophenone, o-nitroaniline, N-2, 3, 4, 6-tetraacetylglucosyl-p-toluidine, 2-bromo-4-methylaniline, 2, 4, 6-tribromoaniline, carbazole, benzylamine, phenylhydroxylamine, nitrosobenzene, hydrazobenzene, azobenzene, azoxybenzene, and p-nitrosodimethylaniline. Of these, phenylhydroxylamine, hydrazobenzene, and p-nitrosodimethylaniline reacted with exactly one mole of periodic acid to respectively form nitrosobenzene, azobenzene, and p-nitrodimethylaniline. Oxidation was not effected with o- and p-aminobenzaldehyde, o- and p-aminoacetophenone, o-nitroaniline, N-2, 3, 4, 6-tetraacetylglucosyl-p-toluidine, carbazole, benzylamine, nitrosobenzene, azobenzene, and azoxybenzene.
Titration curves of codeine and thebaine were compared on titration with p-toluenesulfonic acid in chloroform, acetic acid, dioxane, or 1:1-volume mixture of ethylene glycol and isopropanol and it was found that the curve became gradual in the order of chloroform, dioxane, ethylene glycol-isopropanol, and acetic acid. The coefficient of cubical expansion of solvents often used for non-aqueous titration was measured and it was found that the coefficient of the 1:1 mixture of ethylene glycol-isopropanol is 2.5 times and those of the other solvents 3-4 times that of water. It also showed that acetic acid, which had often been used to date, is not very satisfactory. The coefficient decreases in the order of benzene, chloroform, methanol, isopropanol, acetic acid, dioxane, ethylene glycol-isopropanol, and ethylene glycol. Good results were obtained by the non-aqueous titration of morphine, codeine, thebaine, dihydrocodeine, papaverine, hydroxydihy drocodeinone, and hydrocotarnine by dissolving about 20mg. of each in a chloroform-phenol mixture and titratiog with 0.005Np-toluenesulfonic acid in 1:1 volume mixture of ethylene glycol and isopropanol, using methyl orange as the indicator. A minute amount of the narcotics was determined in a 100-times diluted powder of codeine and dihydrocodeine phosphate, and a cherry bark extract containing 2mg. of dihydrocodeine phosphate in each tablet. The error was within 0.6% in the former two and about 1% in the latter.
It was found that organic compounds in powder form emit fluorescence of various intensities and color tones by the irradiation of ultraviolet light of a definite wave length. Finding that such fluorescence was related to chemical structure of each substance, measurement of the intensity and wave length of the fluorescence was thought to be capable of being an aid for the identification of a substance, discrimination of purity, and the study of chemical structure of organic compounds, and this method was applied to the drugs adopted in formularies, dyes, antibiotics, and crude drugs. As a first step, attempt was made to measure the intensity of fluorescence by the degree of blackening of photographic film and examinations were made on the apparatus of measurement, blackening of sensitizing film, its reproducibility and lineality, and the method of indicating the fluorescence intensity.
An ACTH-like substance was isolated from human placenta at term by glacial acetic acid extraction from acetone-dried powder, zinc acetate fraction, and oxycellulose adsorption. This substance is not a chemical unity, does not show gonadotrophic and prolactin activities, but showed a potency of about 0.9 I. U./mg. by the Sayer method, with ACTH (Schering) as a standard. Potency yield from one placenta was 7-8 I. U.
ACTH fraction (GE) of human placenta was submitted to column chromatography using oxycellulose or starch-succinic ester and the effective principle was found to have collected in the portion eluted with 0.01N hydrochloric acid solution, the portion eluted with 0.1N acetic acid being practically ineffective. Chromatography with starch-succinic ester afforded a fraction having about twice the effect of GF-fraction and its purity was found to be far higher than that of GF-fraction by paper elctrophoresis. However, this fraction was also found to be clearly different from ACTH in dose-response relationship, as was anterior lobe ACTH.
It is known that analyses of refractory compounds, such as thiazole and pyrimidine, by the Pregl-Dumas method give values lower than those calculated. It was found that a satisfactory result can be obtained by weighing the sample into a quartz boat, covering the sample with greyish green nickel oxide, in place of the usual copper oxide, and carrying out the burning.
1, 3, 4, 6, 11, 11a-Hexahydro-2H-8, 9-dimethoxybenzo[b]quinolizine, synthesized through two different routes, were found to be not entirely identical and the compound was again synthesized by another route, by the condensation-cyclization of α-3, 4-(dimethoxybenzyl) piperidine with formaldehyde and hydrochloric acid. As for the properties of four types of benzoquinolizines synthesized to date, (A) and (B) types obtained by the fusion of isoquinoline and pyridine are stable in the air, and (C) and (D) types formed by the fusion of quinoline and pyridine are somewhat labile. It is interesting in comparison with dibenzoquinolizines that the (B) type compounds have the highest melting point among these compounds.
Two new, tertiary non-phenolic bases, named coclamine and coclifoline, were isolated from Cocculus laurifolius DC. (Kohshu-uyaku), besides the many alkaloids found to date. Coclamine: C19H23O3N=C16H14(OCH3)3(-N<), m. p. 140-142°; picrate, m. p. 103-105°; methiodide, m. p. 247° (decomp.); hydrobromide, m. p. 237-240° (decomp.); [α]D4: -245.24° (MeOH). Coclifoline: C19H27O3N=C16H18(OCH3)3(-N<); picrate, m. p. 158-159°. The picrate of m. p. 172° isolated by Kusuda earlier was found to be identical with coclifoline by later purification.
The mechanism of the Wohl-Aue reaction was assumed as the nucleophilic substitution of aniline into the ortho-position of nitrobenzene to form o-nitrodiphenylamine, which undergoes reduction and ring cleavage to form phenazine by the action of excess of aniline as the oxygen-acceptor. Nitrobenzene is oxidized to o-nitrophenol by the action of alkali but this is thought to be a side reaction.
Dehydrogenation of hypognavinol with selenium was carried out and the neutral portion was purified by chromatography. The eluate was separated into the alkylnaphthalene and alkylphenanthrene fractions and crystalline alkylphenanthrene of m. p. 89-90.5° was obtained. This substance was found by mixed fusion and ultraviolet spectral data to be identical with the compound of m. p. 82-84° obtained by the selenium dehydrogenation of anhydroignavinol. Further a minute amount of crystalline alkylphenanthrene of m. p. 187-191° was obtained and was found to be 1, 8-dimethylphenanthrene by mixed fusion and comparison of ultraviolet spectra with the compound (m. p. 189-191°) obtained by synthesis. The third substance was an oily alkylphenanthrene giving a trinitrobenzene complex of m. p. 173-175° (decomp.), which was found by mixed fusion to be identical with the trinitrobenzene complex of m. p. 173-175° (decomp.) obtained similarly from anhydroignavinol. The chromatographic purification afforded basic substances forming a picrate of m. p. 272-275° (decomp.) and a perchiorate of m. p. 273-275° (decomp.). The volatile basic substance obtained was found to be ammonia which formed ammonium picrate of m. p. 285°(decomp.).
Synthesis of phenylalkanolamine by the saccharin method was studied and α-phenyl-β-monomethylaminoethanol, ephedrine, and α-(3, 5-dimethoxyphenyl)-β-monomethylaminoethanol (DMAE) were successfully obtained. There are two methods of preparing α-phenyl-β-monomethylaminoethanol but the one involving reduction of N-phenacylsaccharin (IIIa) to N-(α-hydroxyphenethyl)-o-carboxybenzenesulfonamide (XIa) and its treatment by the usual method gives better yield and requires simpler procedures. The other method of hydrolyzing (IIIa) with alkali is apt to afford a by-product, 3-benzoyl-4-hydroxy-1, 2-benzothiazine S-dioxide (IVa) as yellow crystals. The former method is also advantageous for the preparation of ephedrine, although the acid hydrolysis of N-methyl-N-(β-methyl-α-hydroxyphenethyl)-o-carboxybenzenesulfonamide (XXV) results in the formation of pseudoephedrine, as well as ephedrine. In the case of DMAE, alkaline hydrolysis by this method of (IIIb) did not afford the objective carboxylic acid but only 3-(3′, 5′-dimethoxybenzoyl)-4-hydroxy-1, 2-benzothiazine S-dioxide (IVb) was obtained as yellow crystals and the objective was attained by the former method.
Phenyl-α-pyridylcarbinol compounds (VIII and IX), possessing substituents in the 3- and 4-positions of the benzene ring, were synthesised by the Hammick reaction of picolinic acid, piperonal, and veratraldehyde. Their reduction to the α-benzyl-piperidine compounds (XII and XIII), formylation by heating with fomic acid, dehydrative cyclization with phosphoryl chloride, and reduction with zinc and hydrochloric acid afforded 8, 9-methylenedioxy- (XIV) and 8, 9-dimethoxy-1, 3, 4, 6, 11, 11a-hexahydro-2H-benzo [b] quinolizine (XV).
When an excess of ammonium chloride-ammonia buffer is added to mercuric salt solution, the salt dissolves as an ammonium complex and this complex undergoes substitution with EDTA. This phenomenon was utilized and mercuric salts were directly titrated with compound EDTA standard solution added with magnesium. This method is characterized by the fact that the presence of chlorine does not interfere in titration. The use of mixed indicator of EBT added with methyl red in this titration was found to give a more clear-cut end point than the use of EBT alone. The titration was carried out on mercury bichloride, mercury, yellow mercuric oxide, mild mercurous chloride, and ammoniated mercury, and results comparable to the assay method in the Japanese Pharmacopoeia were obtained.
Antibacterial action of chief decomposition products of thioacetazone was examined with human type tubercule bacilli H 37 RV strain. As shown in Table I, p-aminobenzaldehyde thiosemicarbazone alone was found to have about the same antibacterial action as that of thioacetazone. A 10:1 mixture of thioacetazone and its biological decomposition products was examined similarly and none of the decomposition products seemed to affect the antibacterial action of thioacetazone. In spite of the fact that the blood level of thioacetazone is low and tissue level is said to be generally lower than its blood level, thioacetazone is effective for various kinds of tubercular diseases and it is thought that an indirect action of thioacetazone, besides the direct action on the bacilli, cannot be disregarded.
Paper partition chromatography of coixol by the one-dimensional ascending method using butanol saturated with 27% ammonia water gives a spot at Rf 0.63. Fuming nitric acid was sprayed as the coloring agent. The ether extract of various portions of Coix Lachryma-Jobi L. and C. Lachryma-Jobi L. var. frumentacea MAKINO was submitted to paper partition chromatography, the portion corresponding to coixol was cut out, and extracted with ethanol. Colorimetric determination was carried out with such an extract at the characteristic wave length (291mμ.) of coixol. The amount of coixol was the largest in the root of both plants, a small amount was found in the stem near the root, but only a trace in the upper portion of the stem. Coixol was entirely absent in the fruit and leaves. Although 40 genera and 50 species of Graminae plants were examined, coixol was found in none but the Coix genus.
Seed tuber of Dioscorea Batatas DEONE forma Tsukune MAKINO was planted in a fertilized plot and variation in the content of phosphorus, potassium, nitrogen, and starch during growth of terrestrial stem and leaves and formation of new tubers was examined. Seedling sprouted about 30 days after planting and a new tuber formed 80 days after sprouting, during which there was no marked change in the contents of phosphorus, potassium, and nitrogen in the seed tuber. There was apparent decrease of phosphorus and nitrogen and increase of potassium just prior to the formation of a new tuber but the content calculated by excluding starch remained practically unchanged (Table II). Later, phosphorus and nitrogen decreased, with potassium remaining almost unchanged. The same variation was witnessed in the new tuber, the three inorganic matter seeming to decrease by the rapid increase of starch but the amount excluding starch remained fairly constant. Phosphorus alone decreased with the growth of a new tuber. The amount of phosphorus, potassium, and nitrogen in the total plant from the planting of seed tuber to harvesting is illustrated in Fig. 2 and the rapid increase of these three elements about 90 days after planting indicates that these elements had been adsorbed from outside. It was also observed that no change takes place in the content of these elements in the tuber during winter storage.
2-Methyl-4-amino-5-aminomethylpyrimidine, possessing a -CH2NH2 grouping, reacts with ninhydrin to form Ruhemann purple. Pifer and others utilized this reaction in the colorimetric determination of this compound. The writers examined this method and devised a method with increased accuracy by modifying the conditions, such as the use of a brown-colored vessel to remove the effect of light and use of a buffer solution of pH 4 to make the pH of the test solution constant. In this modified method, the test solution is reacted with 1% ninhydrin, in the presence of pyridine, by warming in a boiling water bath for 30 minutes and the violet solution thereby formed is submitted to colorimetry at 570 mμ. The presence of 2-methyl-4-amino-5-acetamidomethylpyrimidine, sodium acetate, and sodium chloride does not interfere in this determination. Ammonia or ammonium ion does affect the determined value but they can be removed by low-pressure treatment. The accuracy of this method is within ±2%.
The double bond in longifolene resists hydrogenation at ordinary temperature and pressure, using sodium and ethanol, nickel, or palladium as a catalyst. The reduction, however, is easily effected at ordinary temperature and pressure when acetic acid is used as a solvent and platinum as a catalyst, hydrogen being absorbed quantitatively within a short period. Longifolane, the hydrogenation product, is an oily substance similar to longifolene. Its oxidation with chromium trioxide in acetic acid solution, as in the case of longifolene, afforded a small amount of isolongifolic acid and a large amount of a diketone, m. p. 156-157°, as the oxidation products but not longif ofl-1, 2-dione, which is obtained by the oxidation of longif olene. Dehydrogenation of longifolane with selenium also met with strong resistance but an extremely minute amount of cadalene was formed.
About 100 kinds of crude drugs were classified by effective principles and their fluorescence intensity was tabulated by the degree of film blackening, developer sensitivity, and macroscopic tones by the indications previously shown.
Reaction of 3-bromoquinoline with potassium salt of 6-, 7-, and 8-hydroxyquinoline by heating them in the presence of copper powder afforded diquinolyl-3, 6′ (I), diquinolyl-3, 7′ (II), and diquinolyl-3, 8′ (III) ethers. The similar reaction of 3-bromoquinoline and potassium phenoxide gave 3-phenoxyquinoline. The diquinolyl ethers obtained to date are listed in Table I.
α-Glucosidase was applied to the hexasaccharide, composed of glucose, extracted from human placenta, but no change in the reducive action was observed. On the other hand, application of β-glucosidase resulted in the increase of reducive action and glucose alone was detected as the reaction product. From these and previously reported results, it may be concluded that this hexasaccharide is composed of 6 molecules of glucose bonded in β-type, C1 to C4, in a chain.
3, 5-Dimethoxyphenacyl halide (IX), an important intermediate for the preparation of α-(3, 5-dimethoxyphenyl)-β-monomethylaminoethanol (DMAE), can be obtained by the application of diazomethane to 3, 5-dimethoxybenzoyl chloride (VI) and subsequent decomposition of the diazoketone compound (VII) so formed with mineral acid, or the application of dimethylcadmium or acylmalonic ester to (VI) and bromination of the methyl ketone compound thereby formed. (IX) is derived to the amino ketone compound (XII) by the application of methylbenzylamine, its Meerwein reduction to the amino alcohol compound (XIII), and finally by debenzylation with palladium to DMAE. Application of dimethylamine to (IX) and reduction with nickel affords methyl-DMAE. The uterus contracting action of DMAE and methyl-DMAE on excised rabbit uterus by the Magnus method and their toxicity to mice are listed in Table I. DMAE is approximately the same as 6-allyl-2-methoxyphenyl diethylaminoethyl ether (AMAE) but the potency of methyl-DMAE was very slight.
The Ullmann reaction of 7, 8-dibromoquinoline and pyrocatechol did not afford the desired benzo[7, 8]-p-dioxino[2, 3-h]quinoline (II) but the same reaction with 7-bromo-8-hydroxyquinoline and o-bromophenol successfully gave (II). The same reaction of 6-hydroxy-7-bromoquinoline and o-bromophenol afforded benzo[6, 7]-p-dioxino[2, 3-g]quinoline (IV). The Ullmann reaction of 7-hydroxy-8-bromoquinoline alone yielded a minute amount of a substance assumed to be the objective pyrido [2, 3-α]pyrido[2, 3-h]dibenzo-p-dioxine (II) but could not be identified. An attempt to obtain pyrido[2, 3-h]pyrido[2, 3-i]dibenzo-p-dioxine (V) by the same reaction on 6-hydroxy-7-bromoquinoline did not materialize, nor the Ullmann reaction of 7-bromo-8-hydroxyquinoline.