Starting with 2, 4-dihydroxy-5-alkyl-benzaldehydes, following were prepared by the Perkin's reaction: 7-Acetoxy-6-methyl-coumarin, 7-acetoxy-6-ethylcoumarin, 7-acetoxy-6-n-butyl-coumarin, 7-acetoxy-6-isoamylcoumarin, 7-acetoxy-6-n-amylcoumarin, and 7-acetoxy-6-n-hexylcoumarin. Deacetylation gave the respective 7-hydroxy compounds: -6-methyl-, m.p. 246°; -6-ethyl-, m.p. 156°; -6-n-butyl-, m.p. 140°; -6-isoamyl-, m.p. 118°; -6-n-amyl-, m.p. 96°; and 6-n-hexyl-m.p. 100°. 7-Hydroxy-6-n-heptylcoumarin, m.p. 103°, and the above described hydroxycoumarins except 6-methyl derivative were also synthesized by Pechmann reaction from 4-alkylresorcinols, malic acid and H2SO4.
Acyl-thiamine hydrochloride was obtained by the reaction of AgCl with acyl-thiamine hydrobromine produced by the condensation of 2-methyl-4-amino-5-bromomethyl-pryimidine hydrobromide and 4-methyl-5-β-acyloxyethyl-thiazole. Benzoyl, acetyl, propionyl, butyryl, isovaleryl, caproyl, isocaproyl and heptoyl were used as the acyl radicals.
In order to examine the efficacy of helminthics, some resorcinol derivatives were synthesized. (1) Hexylresorcinol dicarbamate, m.p. 181-182°. (2) Hexylresorcinol dicarbethoxylate, oil. (3) 6-Chloro-4-alkylresorcinols (where alkyl was: ethyl, propyl, butyl, amyl, isoamyl, hexyl, heptyl, octyl). All of these chlorine derivatives, except the ethyl derivative, combined one molecule of water of crystallization to form stable crystals. As to the anthelmintic power of those derivatives, those with 5-8 carbons in their alkyl radical were the strongest, while irritation of mucous membrane was weaker that of hexylresorcinol in those with alkyl group of 6-8 carbons. (4) 2, 6-Dichloro-4-alkylresorcinols (alkyl: hexyl, isoamyl, amyl) showed neither irritant properties nor anthelmintic action. (5) 6-Bromo-4-alkylresorcinols had very weak anthelmintic action.
The relation between the speed of reduction and the shape of zinc used in the reduction of alkylylresorcinol to alkylresorcinol by Clemmensen's method was examined and the results showed that larger the surface of zinc, faster the reduction speed.
Formylacetone-anil and guanidine were boiled in alcohol on a water bath for one hour in the presence of sodium ethoxide, and 2-amino-4-methylpyrimidine was obtained in a 70% yield. Sulfamerazine was synthesized by the same method in a 15% yield using sulfaguanidine. Sulfamerazine is also obtained by fusing formylacetone-anil and sulfaguanidine in the presence of NaOH in a yield of 60%. 2-Aminopyrimidine was obtained by boiling for 4hrs. malonedialdehyde-dianil and guanidine in alcohol in the presence of sodium ethoxide, in a yield of about 30%. In this reaction, sulfadiazine was not obtained by the use of sulfaguanidine.
An attempt was made to apply the van Slyke's method used in the quantitative determination of amino acids for heterocyclic amino compounds. 2-Aminopyridine derivatives were able to be determined and were not affected by the presence of other substituents. Diazonium compound of 3-aminopyridine was stable but its stability was influenced by both temperature and other substituents. 2-Aminothiazole derivatives can also be determined, but about twice the theoretical amount of gas is produced from 2-amino-4-methylthiazole. Hydrogen in 5-position was assumed to take part in this reaction, since 2-amino-4-methyl-5-ethanol-thiazole gave the same result as for 2-aminothiazole. It was found difficult to liberate nitrogen gas from guanidine by van Slyke's method, but when 2-aminopyrimidine derivatives were produced by pyrimidine nucleus formation, nitrogen gas was liberated quantitatively. Diazonium compound of 4-aminopyrimidine derivatives was stable.
It was found that 4-methyl-5-β-hydroxyethylthiazole can be synthesized from 2-amino-4-methyl-5-β-hydroxyethylthiazole in a good yield. 2-Bromo-4-methyl-5-β-hydroxyethylthiazole is obtained by thermal decomposition of diazoperbromide of 2-amino derivative of the starting material, and its reduction easily yields the objective 4-methyl-5-β-hydroxyethylthiazole.
Of the Chinese drug prescriptions resistered in the National Formulary (Japan), antibacterial activities were examined of 51 prescriptions, used in bacterial diseases, of 11 other prescriptions, and, futher, of 35 kinds of crude drugs composing their effective principles, with following results. (1) Almost all Chinese drug prescriptions applied in bacterial diseases possessed growth inhibition against Staphylococcus and B. coli, although the degree of effectiveness varied more or less. (2) The antibacterial crude drugs have increased growth prohibiting actions when used in prescriptions and in a concentrated state in case of prescriptions, than when used only by itself. (3) Both prescriptions and crude drugs generally possessed strong growth inhibiting activities against Staphylococcus but a weak against B. coli.
The antibacterial properties of 164 kinds of wild plants collected around Maebashi, Ome, the foot of Mt. Akagi, Ikaho and Haruna, during March to May, 1949, against Staphylococcus aureus were examined, and 35 kinds, i.e. 20%, were found to be effective. The names of plants tested and their effective portions are given in the table.
The antibacterial properties of 148 kinds of wild plants collected around Maebashi, the foot of Mt. Akagi, Haruna and Shinshu-Bessho, during May to June, 1949, against Staphylococcus aureus were examined, and 56 kinds, i.e. 38%, were found to be effective. The names of plants tested and effective portions are given in the table.
The antibacterial properties of 118 kinds of medicinal plants, cultivated in the Experimental Station for Medicinal Plant Cultivation, Tokyo Hygienic laboratory, Welfare Ministry, Kasukabe, offered for tests on July 13, 1949, were examined against Staphylococcus aureus by the same method as the previous papers. 39 kinds, i.e. 33%, were found to be effective. The names of plants tested and effective portions are given in the table.
The antibacterial properties of 154 kinds of wild plants gathered around the foot of Mt. Asama, Ikaho, Haruna, and Maebashi, during July to August, 1949, against Staphylococcus aureus were examined. In the present experiments, the sterilization of bouillon after water extract was added was changed to the pressure sterilization of 15 lbs. at 115°, for 15mins. 80 kinds (52%), were found to be effective. The names of plants tested and effective portions are given in the table.
Plants living in and around water, and ferns that were heretofore not taken up, were chiefly taken into consideration and antibacterial activities against Staphylococcus aureus were examined of 154 kinds collected around Ikaho, Kusatsu, Azaminuma, Ogo and Maebashi during August to September, 1949, by the same method reported previously. Among them, 83 kinds, 54%, were shown to be effective. The names of plants tested and effective portions of the plants are given in the table.
Special emphasis was laid on ferns and aquatie plants and the antibacterial properties against Staphylococcus aureus were tested of 151 species collected around Akagi cattle farm, Mt. Ohmine, Lake Tatara, Bessho hot springs, and Maebashi. 65 kind, 43% of them, were found to be effective. The names of plants tested and effective portions of the plants are given in the table.
The influences of some drugs upon M. tuberculosis and the measurement of the amount of oxygen consumption, measured by the Warburg's manometer, and at the same time, the growth inhibiting activities using Kirchner's culture medium, in which 10% of serum was added, were compared. 31 compounds were tested; i.e. 10 of resorcinol compounds; 7 of lichen, substances 6 of coumarin compounds, 8 of plant components and synthesized products. There are many types in consuming oxygen, and among them usnic acid, monochlorocyclohexylresorcinol, showed the strongest inhibiting action to oxygen consumption. Usnic acid and p-aminosalicylic acid were the strongest in inhibiting growth, 2, 4-dihydroxy-3-chloro-5-n-amylbenzaldehyde, 2, 4-dihydroxy-3-chloro-5-n-hexylbenzaldehyde followed these products. It was shown that the inhibiting action to oxygen consumption and the growth inhibiting activities were not always parallel.
The constitutional formula of phthioic acid is not the trialkylacetic acid formula presented previously, but is assumed to be 3, 13, 19-trimethvltricosanoic acid formula reported by Polgar and Robinson. An attempt was made to synthesize the acid by the method different from that of Polgar and his co-workers. In order to get the acid by Kolbe's electrolysis of 6-methyldecoic acid (I) and 2, 12-dimethyltridecane-1, 13-dicarboxylic acid monoester (II), 2, 11-dimethyldodecane-1, 12-dicarboxylic acid (III) was synthesized from adipic and sebacic acids, respectively, to determine the synthetic method of (II), and it was found that the yield of the synthesis from sebacic acid was better than that from adipic acid.
In order to obtain 3, 13, 19-trimethyltricosanoic acid, which is assumed to be the structure of phthioic acid, by the Kolbe's electrolytic condensation of 6-methyldecanoic acid and ethyl hydrogen 2, 12-dimethyltridecane-1, 13-dicarboxylate 11, 15-dimethylpalmitic acid was prepared by the Kolbe's electrolytic condensation of dihydrorhodinic acid and ethyl hydrogen sebacate, as a model experiment of electrolytic reaction, with an yield of 31%. In this reaction, 2, 6, 9, 13-tetramethyltetradecane and hexadecane-1, 16-dicarboxylic acid were recognized to be byproducts.
In order to obtain 3, 13, 19-trimethyltricosanoic acid, which was the Polgar-Robinson formula of phthionic acid, 6-methyldecoic acid and 2, 12-dimethyltridecane-1, 13-dicarboxylic acid monoethyl ester, were synthesized and the objective compound was obtained by the Kolbe's electrolysis of these two compounds. 5, 14-Dimethyloctadecane and 2, 12, 15, 25-tetramethylhexacosane 26-dicarboxylic acid were identified as the byproducts of this electrolysis.
We obtained o-thiocresol the final product, by the electrolytic reduction of o-toluenesulfonchloride in alcoholic sulphuric acid solution in which lead pole is used as cathode, and at the same time, o, o′-ditolyldisulfide, o, o′-ditolydisulfoxide, o-toluene-sulfonic acid were obtained as the intermediate products. These products conincide with the ones which we obtained in the electorlytic reduction of p-toluenesulfonyl choloride. But there was a difference of the current efficiency, in the reduction between p-compound and o-compound. As to o-compound, sulfinic acid and disulfoxide were reduced in good current efficiency but that of disulfide was not so good. Differing from the case of p-compound, the production of -disulfoxide followed that of sulfinic acid in case of o-compound. These results showed that the reductive reaction might be proceeded in a different mechanism in the cases of o-compound and p-compound respectively.
Mold grew in the existence of n-propyl-p-hydroxybenzoate at the concentration of ca. 0.001%, 0.003%, 0.005%, and 0.007% respectively after 4, 5, 6, and 8 days, but ca. 0.005% of thymol, 0.003% of p-chlorothymol, and 0.001% of o-chloro-p-thymolinaldehyde inhibited the growth of mold during 30 days experimental period. These results showed that, thymol group compounds had a strong antiseptic action against mold in soy bean sauce. The experiment of urea, thiourea had not antiseptic power in the concentration of 0.01%.
An improved type vacuum tube potentiometer and calomel electrodes were manufactured and used in the presennt experiment. Glass electrodes were also experimentally manufactured from soft, hard and McInnes glasses into diaphragm-type electrodes. As a result of a determination of the relationship between E. M. F. and pH, McInnes glass was found to be the most suitable. pH of blood, saliva and urine was determined using this electrode.