Thermal analyses were carried out between various barbital derivatives and these as one component and urea, succinimide, and bromodiethylurea as the second component. With the 18 kinds of solid-liquid equilibrium diagrams thereby obtained, relationship between the ability for molecular compound formation and structure of the components was examined.
Dimethylalkyl-(o-methoxy) phenylammonium bromide (alkyl=butyl, hexyl, octyl, and dodecyl) and dimethylalkyl-(o-dodecyloxy) phenylammonium bromide (alkyl=butyl, octyl, decyl, dodecyl, and tetradecyl) were prepared and their antibacterial action against human type tubercle bacilli was examined in Kirchner's medium. It was found that the latter group possessed some antibacterial action while the former only possessed a weak action and that the length of the alkyl chain, at least up to C12, had no effect on the antibacterial action. Comparison of the effect of O-alkyl and N-alkyl groups on the antibacterial action showed that the size of the alkyl group in O-alkyl did cause a marked difference in the antibacterial action while that of the latter was ineffectual, at least up to C12.
It has previously been shown that crystals of m.p. 105-106°, C10H14O, had been obtained as the component of the essential oil of Chenopodium ambrosioides L. The molecular composition is now corrected to C20H28O2, confirmed as the dimer of l-pinocarvone, and its structure was assumed as follows:
Although the structure of kokusaginine has been determined by Anet et al., it was also confirmed by the following procedure. Catalytic reduction of kokusaginine with PtO2 in ethanolic solution produced colorless cubic crystals of the formula, C14H17O4N (IV), m.p. 182-183°, which by demethylation with conc. HCl, gave the compound, C13H15O4N (V), m.p. 263-264°. With acetic anhydride and pyridine it yielded a monoacetate, C15H17O5N, m.p. 235-236°, in colorless prisms. (IV) and (V) are assumed to be 3-ethyl-4, 6, 7.-trimethoxycarbostyril and 6, 7.-dimethoxy-3-ethyl-4-hydroxycarbostyril, respectively, as in the case of dictamnine, skimmianine, and kokusagine. On the other hand, the compound (V) was prepared synthetically as follows: Methyl 6-aminoveratrate and butyric anhydride gave methyl 6-(N-butyrylamino) veratrate (X), m.p. 107.5-108.5°, which, when treated with Na in toluene, afforded 6, 7.-dimethoxy-3-ethyl-4-hydroxycarbostyril, m.p. 263-264° (monoacetate, m.p. 235.5-236°). This substance is identical with (V) (as was also the acetate). The structure of kokusaginine, therefore, is 6, 7.-dimethoxydictamnine.
Saponification of santonin (I) followed by oxidation in pyridine with chromium trioxide afforded 3, 5-dioxosanta-1, 4-dienic acid (VI), m.p. 134-135°. Reduction of its methyl ester with zinc and acetic acid yielded methyl 3, 5-dioxosantanate (VIII), m.p. 79-81°, and its saponification gave the acid (IV), m.p. 145-147°. These diketonic acid and its ester were identical with those obtained from tetrahydrosantonin (II) by the similar mode of oxidation, as described in the previous paper.
The reaction whereby thiamine transits reversibly to the thiol type by alkali in aqueous solution was followed by the potentiometric method. The reaction rate of thiamine salts with alkali or acid is extremely rapid at below pH 7 and slow at above that pH. The rate is greater at higher temperatures and is independent of the thiamine salt used or the kind of acid added. pKa values of various pure thiamine salts were measured at 0° to 50° and the values were found to be smaller at higher temperatures, and independent of the kind of thiamine salts used. From these results, it was found that the equilibrium of thiamine and its thiol type is extremely dynamic and it was assumed that there is a possibility of the presence of the thiol-type thiamine under physiological conditions.
1) Equilibrium concentrations of thiol-type thiamine at various pH and temperature were measured from anodic wave height by polarography and it was confirmed that thiol-type thiamine can exist under physiological conditions. 2) Reaction between p-chloromercuribenzoate (PCMB) and thiamine was followed by polarography. Since the reduction wave of PCMB decreases rapidly at pH 9.2 and slowly at pH 6.8, it was seen that thiamine-thiol is formed from thiamine salts. 3) The rate of the formation of thiamine-thiol is practically independent of the kind of the thiamine salt.
Several kinds of thiazole derivatives were prepared by heating the thioimidoether hydrochloride obtained by bubbling dry hydrochloric acid gas through the mixture of a nitrile and α-thioketone. This is a new method for preparing thiazoles and makes it possible to introduce suitable substituents in 2, 4, and 5 positions of the thiazole ring by the choice of suitable nitriles and α-thioketones.
During the condensation of ammonium dithiocarbamate (I) and γ-aceto-γ-chloropropyl alcohol (VI) to form 2-mercapto-4-methyl-5-β-hydroxyethylthiazole (VIII), an intermediate (VII) of m.p. 139° was obtained. Condensation of (I) and γ-aceto-γ-chloropropyl acetate (X) also yielded an intermediate (XI), sparingly soluble in benzene and showing the same m.p. 105° as that of 2-mercapto-4-methyl-5-β-acetoxyethylthiazole (XII). (VII) and (XI) easily liberated one mole of water on heating and changed respectively to (VIII) and (XII). Acetylation of (VIII) yielded (XII) but acetylation of (VII) did not afford (XI), and structurally unknown yellow needles, m.p. 62-63°, were obtained. Ultraviolet absorption spectra of (VII) and (XI) are clearly different from those of (VIII) and (XII) and they are assumed to be 4-methyl-4-hydroxythiothiazolidone-2.
By the alkylation of 2-mercapto-4-methyl-5-β-hydroxy (or acetoxy) ethylthiazole (I or IV) with alkyl halides or dialkyl sulfates, corresponding alkylthio compounds (III or V) were prepared. Their reduction and desulfurization with aluminum amalgam or zinc dust afforded 4-methyl-5-β-hydroxy (or acetoxy) ethylthiazole (II or VII) in a good yield. The basicity of alkylthio compounds (III) decreases as the alkyl group becomes larger, with increased resistance to reduction. The benzylthio compound forms toluene and 2-mercapto-4-methyl-5-β-hydroxyethylthiazole by the reduction, and benzyl alcohol and 4-methyl-5-β-hydroxyethylthiazole by oxidation with hydrogen peroxide, differing in properties from those of the lower alkylthio compounds described above.
Condensation of 2-methyl-4-amino-5-bromomethylpyrimidine hydrohromide (I) and 2-mercapto-4-methyl-5-β-hydroxyethylthiazole (II) yielded the thioether type 2-(2′-methyl-4′-aminopyrimidyl-5′)-methylthio-4-methyl-5-β-hydroxyethylthiazole (III), m.p. 187-188°. Oxidation of (III) with hydrogen peroxide afforded 2-methyl-4-amino-5-hydroxymethylpyrimidine (IV) and 4-methyl-5-β-hydroxyethylthiazole (V), while its reduction with aluminum amalgam resulted in the formation of 2, 5-dimethyl-4-aminopyrimidine (VI) and (II). These properties agree with those of 2-benzylthio-4-methyl-5-β-hydroxyethylthiazole (VII). Application of (I) to (VII) gave (III) but the application of (I) to 2-methylthio-4-methyl-5-β-hydroxyethylthiazole (X) resulted in the formation of thiochrome (XII).
Isonicotinic acid hydrazide derivatives and allied compounds were prepared and the antibacterial tests in vitro were carried out with Mycobacterium tuberculosis A. T. C. C. No. 607. In general, it may be said that the hydrazone-type compounds of INAH showed antibacterial power about equal to that of INAH, methyl furyl-2 ketone isonicotinylhydrazone showing especially strong antibacterial action, with effective inhibitory concentration of 10-8mole. Such a fact suggests that the presence of an isonicotinyl group in the molecule is necessary in order that these compounds show antibacterial action. The hydrazide of p-aminosalicylic acid also showed some antibacterial action though the action entirely disappeared on substituting the hydroxyl with chlorine, methoxyl, or ethoxyl. The antibacterial action appears again if the amino group is changed to the nitro group.
The solubility of cuprous iodide is less than the order of 10-5mol/L., and it is insoluble in 0.1N sulfuric acid. It is assumed from such facts that cuprous iodide may be quantitatively precipitated from sulfurous acid solution. It has been confirmed by experiments that iodine can be determined satisfactorily by weighing the cuprous iodide precipitated with copper sulfate from sulfurous acid solution. The cuprous iodide precipitate can be washed with water without any dissolution or peptization. By washing the precipitate consecutively with water, a little acetone, and ether, and drying at 110-120° for one hour or so, constant weight is obtained.
The antibacterial action of 1, 4-naphthoquinones substituted in 2- or 2, 3-positions vary in accordance with the substituents. The compounds with a strong antibacterial action also inhibit the growth of fungi and yeast (Table I). These substituents effect prolongation of the induction period in bacterial growth and the antibacterial action of these compounds decreases by reduction (Figs. 1 and 2). Reduction potential of 2- and 2, 3-substituted 1, 4-naphthoquinones were measured (Table II). Comparison of the reduction potential and the antibacterial power examined by the cup method showed (Table III) that the two values went in parallel. The antibacterial mechanism of the 1, 4-naphthoquinone derivatives here synthesized was assumed to be as follows: In 2-monosubstituted quinones, such a reaction mechanism involves growth inhibition chiefly by combination with SH-group, essential to bacterial growth, and in 2, 3-disubstituted derivatives, the compounds behave as the hydrogen carrier with oxygen as the direct acceptor and inhibit growth by effecting bacterial respiration with abnormal oxidation, while recovering the quinoid form.
In order to test the antibacterial action, 10 kinds of thiazolylamino derivatives possessing diphenyl ether as the fundamental structure and with substituents in various positions, listed in Table I, and two kinds of biphenyl ene oxide derivatives possessing thiazolylamino group, listed in Table II, were prepared. It was found that antitubercular action is strengthened by the introduction of a thiazolylamino group into diphenyl ether, the action seeming to be stronger when such a group is in ortho-position.
As prelimnary experiments in finding the requisite metal in Trichophyton, detection of elementary inorganic composition in the fungal body was carried out by the spectroscopic analysis, using four strains, i.e. Trichophyton interdigitale, T. purpureum, T. asteroides, and Epidermophyton inguinale. These dermatophytes were cultured in an ordinary Sabouraud medium, Landis medium which is suited for spore formation, and in Fulmer medium which does not contain organic nitrogen. The fungal body harvested from each medium was ignited, and the residual ash was analyzed. As the chief componental elements, P, K, Mg, Ca, an dNa were found, and Fe, Al, and Cu as the minor componental elements. Fifteen elments were also found as the microcomponental element. The metals not detected were As, Bi, Co, Hg, and Li. There was no characteristic in the elements found by different strains and it seems that the kind and amount of elements found in the fungal body are dependent on the composition of the medium.
The present series of experiments were undertaken in order to clarify the fungal components of Trichophyton, through the biological properties of the fungus, and especially their relationship with pathogeniety. Trichophyton asteroides cultured on Sabouraud medium at 25° for 30 days, was harvested, washed with water, and dried. This was then consecutively extracted with ether, acetone, ethanol, and water. The ether extract yielded ergosterol (2-4.6% of the dried fungi), and leucine, valine, alanine, and glycine were detected from the ethanolic and aqueous extracts. It was thereby realized that these amino acids are present in the free states in T. asteroides. The isolated leucine showed lower value in optical rotation and there is a possibility that the D-type, not present in natural products, is present. The ether extract from which ergosterol was removed as much as possible, was dissolved in liquid paraffine and repeatedly given as a peritoneal injection in mouse which killed the animals.
Quantitative determination of amino acids, detected from the 50% ethanolic extract of Trichophyton asteroides, was carried out using starch column chromatography. The values (percentage against dried fungal growth) were: 2.1% leucine, 1.5% valine, 0.8% alanine, 0.2% glycine, and 0.1% aspartic acid, making a total of 4.7%. Aspartic acid was detected by the previous paper chromatography. In order to examine the distribution of these amino acids in Dermatophytes, similar examinations were carried out on 7 strains: T. asteroides, T. interdigitale, T. purpureum, Ach. Schoenleini, M. japonicum, Ach. gyseum, and E. inguinale, and all afforded leucine, valine, alanine, and glycine. The significance of these free amino acids in Dermatophytes is still unknown. Since intracutaneous injection of these amino acids, alanine and glycine, sometimes leucine, caused itching, at least one part of itching by Dermatophytes is assumed to be due to the presence of itch-inducing amino acids.
1) It was found that, in the solubilization of vitamin A and vitamin D2, surface active agents of the ricinoleic acid polyhydroxyethylene ether series possessed the same or better efficiency than various surface active agents of the Tween, Myrj, and Brij series. 2) Hydrophilic-lipophilis balance (shown by HLB) and solubilizing efficiency of various surface active agents were examined systematically and a definite and regular relationship was found to exist. The relationship between solubilizing efficiency and HLB between vitamin A palmitate and vitamin A alcohol or vitamin D2 showed an inverse tendency. 3) Solubilization of vitamin A palmitate was found to be greatly affected by the change in HLB of the surface active agents.
Effect of the removal of pyrogen through quinone treatment and its reaction course were studied by polarography and this result was used in elucidating the mechanism of pyrogen removal by this means. 1) Pyrogen culture filtrate, even in a dilute solution, was found to possess extremely great action of inhibiting maximum oxygen wave and the limit of detection was 1γ/cc. as converted to the concentration of casein. 2) Pyrogen was separated into Pα and Pβ (cf. next paper) by electrophoresis and maximum oxygen wave of each was measured. Both were found to show inhibitive action. 3) The solution obtained by the treatment of pyrogen culture filtrate or pyrogenic glucose parenteral solution with quinone, giving negative tetrabromophenolphthalein (TBP) reaction, is entirely devoid of suppression of maximum wave and did not indicate the presence of pyrogen by polarography. Polarographic examinations were made with sodium citrate and pyrogenic substances giving positive TBP reaction, such as egg albumin, casein, peptone, nucleic acid, brucine, and 8-hydroxyquinoline. They all gave similar results. 4) The foregoing samples were treated with quinone and the activated carbon thereby obtained was digested with redistilled water, affording solution giving positive TBP reaction and again showing suppression of maximum wave.
The true nature of pyrogen and changes in the behavior of pyrogen after quinone treatment were studied through filter paper electrophoresis. 1) Electrophoresis of pyrogen-containing culture filtrate showed that pyrogen with positive TBP reaction was composed of electrically almost neutral portion (Pa) and positively charged one (Pβ). 2) Pα is removed well by adsorptives and ion exchange resins but the removal of Pβ is difficult. This fact well explains the observations (cf. previous paper) that some existing method of purifications were not necessarily effective in removing pyrogen. 3) The solution obtained by the treatment of pyrogen-containing culture filtrate with quinone and then activated carbon gives negative TBP reaction and such image is not detected by electrophoresis. 4) Electrophorectic examination of pyrogenic glucose injections gave the same results as those with the culture filtrate.
Effect and mechanism of pyrogen removal by quinone treatment were examined spectrochemically. 1) The simple solution of culture filtrate containing pyrogen used in the present series of experiments showed a slight shoulder of absorption at 260mμ but did not show any absorption spectrum which would offer evidence of a presence of pyrogen. 2) On the application of quinone to the pyrogen-containing culture filtrate, the optical density of quinone itself in the ultraviolet region decreased, the solution acquired a reddish color, and there appeared an absorption maximum at 390mμ. As an example of pyrogenic substance, albumin was treated with quinone and in this case, optical density at 420mμ increased together with the increase in the red color. These facts confirm that a reaction product (PQ) has been formed between pyrogen and quinone. 3) Pyrogen-containing filtrate solution and substances giving positive TBP reaction, when treated with quinone and activated carbon to solutions negative to TBP reaction, do not show any absorption and confirm the removal of pyrogen spectrochemically. 4) The activated carbon used for quinone treatment was digested with water and this solution showed the absorption again, indicating that the pyrogen adsorbed on the carbon had been dissolved out. Summarizing these results, the following reaction mechanism earlier assumed seemed appropriate even from spectrochemical examinations. P+Q→PQ (reaction between quinone and pyrogen) PQ+C→CPQ (adsorptive removal of PQ by activated carbon) CPQ→CQ+P (liberation of pyrogen)
Using glass-calomel electrode, hydrochlorides of 1-phenyl-2-aminopropane derivatives can be accurately titrated in anhydrous acetic acid with perchloric acid, if mercuric chloride is added more than the same equivalent of the sample. However, the sulfate and phosphate of these derivatives cannot be so accurately titrated as the former, because the acidity of sulfuric and phosphoric acid appear a little in anhydrous acetic acid. These derivaties can be also determined practicably using crystal violet as an indicator, except the sulfate. It seems from the titration curves that the basicity of dl-1-phenyl-2-aminopropane is the weakest, and it increases a little in the following order: d-1-Phenyl-2-methylaminopropane, l-ephedrine, and dl-1-pheny-2-dimethylaminopropane, and the strongest of these is dl-methylephedrine.
Using the usual tabletting machine used in the factory and without changing the amount of granules supplied, two kinds of granules were submitted to tabletting at a constant tabletting speed, the same mortar volume, and in three positions of the upper pounder (giving three different thicknesses of tablet), and correlation between the forming pressure measured and various characters of the products was examined. From such results, following points were clarified: 1) Naturally, there was no relation between pressure and weight of the tablet but differentiation by the position of the upper pounder (thickness of tablets) showed that there existed a positive correlation within each stratum. Appearance of such correlation in the case of one of the granules was found to be the interference of the change in the amount of granules supplied into the factor of the position of the upper pounder. 2) There is a negative correlation between pressure and thickness but differentiation by the thickness indicated the presence of a positive correlation. This indicates that there is a positive correlation between weight and thickness. 3) There is positive correlation between pressure and the quotient of weight by thickness. 4) There is a positive correlation between pressure and compressive strength. 5) Within the conditions used in the present experiments, no difference was found in the results from two kinds of granules.
Tabletting pressure was measured by tabletting two kinds of granules by three-step velocity, using the same tabletting machine, mortar volume, and upper pounder position. Examination was made as to correlation betetween such values and various characteristics of the product. It was thereby found that (1) correlation between tabletting speed and pressure was not significant, and (2) correlation between tabletting pressure and characteristics of various products showed the same tendency as described in the previous report.
Addition of tertiary amines to the acetic anhydride solution of citric, aconitic, and malonic acid and heating causes red, violet, or blue coloration, while other organic acids do not show such coloration. This reaction is the most sensitive coloration peculiar to aliphatic, alicyclic, aromatic-aliphatic, and aromatic tertiary amines. The procedures of such coloration are as follows: To a minute quantity of tertiary amines (aqueous solution is evaporated to dryness after acidification with hydrochloric acid) or 1 drop of their ethanolic solution, 0.5cc. of 2w/v% acetic anhydride solution of citric acid is added, and the mixture is warmed in a water bath by which red to purple coloration results. The reaction vessels to be used must be clean and a blind test is carried out at the same time. Alkali and alkali earth metal salts of organic and inorganic acids also give positive reaction but other metal salts are negative.
As a preliminary to the synthesis of methoxydepsidan (VI), a fundamental structure of insularine (I), the alkaloid of Cyclea insularis (Makino) Diels, several of its intermediates were prepared. 2, 3-Dimethoxydiphenyl ether-2′-carboxylic acid (IX) was prepared through the route shown in Fig. 1 but the yield from its Ullmann condensation was extremely poor. Methyl 2-amino-3-methoxydiphenyl ether-2′-carboxylate (XIV) was prepared by the route shown in Fig. 2 and attempt was made to decompose its diazonium salt to change the amino group with a hydroxyl but the objective substance was not obtained, and a substance in which the amino group had liberated, i.e. 3-methoxydiphenyl ether-2′-carboxylic acid (XV), a substance assumed to have undergone diphenyl condensation, i.e. 1-methoxydibenzofuran-6-carboxylic acid (XVI), and one other crystalline substance were obtained instead.
By the route shown in Fig. 1, 2, 3-dimethoxy-2′-(hydroxymethyl) diphenyl ether (VIII) was prepared which was treated with hydrobromic acid. 2-Amino-3-methoxy-2′-(hydroxymethyl) diphenyl ether (XII) was also prepared and the decomposition of its diazonium salt was carried out but an intermediate which could be derived to the objective methoxydepsidan was not obtained. Decomposition of the diazonium salt of 2-amino-3-methoxydiphenyl ether-2′-carboxylic acid (XIII) also failed to yield the objective compound with the amino group replaced by hydroxyl and a minute amount of 1-methoxydibenzofuran-6-carboxylic acid (XIV) alone was obtained.
Attempt was made to carry out the decomposition of the diazonium salts of 2-aminodiphenyl ether-2′-carboxylic acid (IX) and its methyl ester (IV) to obtain the corresponding 2-hydroxy derivatives. However, the amino acid ester (IV) easily underwent cyclization with even diluted mineral acids, such as a 1% solution, not to say conc. mineral acids, to form the corresponding lactam (V) at an ordinary temperature and it was found difficult to obtain the aqueous solution of its diazonium salt. The free amino acid (IX) also possessed some tendency to form the lactam but it was possible to obtain the aqueous solution of its diazonium salt. Therefore, 2-amino-diphenyl ether-2′-carboxylic acid (IX) was derived to its diazonium salt and its decomposition products were examined in detail. It was thereby found that, although the objective 2-hydroxy compound was not obtained, salicylic acid was obtained in 4.2% yield against the starting material indicating the fact that during the decomposition of the diazonium salt, severance of the ether-bonding oxygen, forming the diphenyl ether, had taken place.
Observations were made on the change of the solubility of α-tocopheryl acetate in 10% aqueous solution of surface active agents of polyoxyethylene series by temperature. It was thereby found that: (1) By keeping the lipophilic group of the surfactant constant and increasing the size of hydrophilic group, solubility decreases and the clouding point rises; (2) on keeping the hydrophilic group constant and increasing the lipophilic group, there is no definite regularity in the change of solubility; (3) on keeping the temperature constant and increasing the amount of α-tocopheryl acetate added, there is a change from clarification to turbidity to clarification to turbidity, the same changes occurring also in the case of gradually raising the temperature of α-tocopheryl acetate of a suitable concentration; (4) the foregoing phenomenon is assumed to occur through the presence of some molecules with small amount of oxyethylene group, which happens in some of the surfactants; and (5) a sample which is turbid at low temperature, when warmed to the clouding point and gradually cooled, still remains turbid but sometimes becomes clear if cooled rapidly.
Action of alkali against aldehydes causes either Cannizzaro reaction or formic acid decomposition and it was assumed that the formic acid decomposition occurs on suppression of the Cannizzaro reaction by the nature and steric interference of the carbon atom carrying the aldehyde group. The aldehyde group in trans-π-oxocamphor is attached to the bridged carbon that the α-carbon assumes a σ-polarity and the Cannizzaro reaction is thereby suppressed, causing formic acid decomposition alone. Such behavior suggests α, β-unsaturated aldehydes and the bridged carbon in camphor seems to possess a double-bond-liki characters. On the other hand, the aldehyde in 10-oxocamphor was assumed to be a tertiary aldehyde and to undergo Cannizzaro reaction, though in a minute amount, besides formic acid decomposition, since its α-carbon atom possesses σ+polarity.
1) Eighteen kinds of new 5-substituted (CH3, H) 2-benzylidenehydrazino-1, 3, 4-thiadiazoles were prepared by the condensation of 5-substituted 2-hydrazino-1, 3, 4-thiadiazole and aromatic aldehydes, and their antibacterial power were examined. 2) 5-Substituted 2-hydrazino-1, 3 4-thiadiazoles were obtained either from 5-substituted 2-amino-1, 3, 4-thiadiazoles by diazotization through 5-chloro compound and application of hydrazine hydrate, or from 5-nitrosamino or 5-nitramino compound by reduction with zinc dust and acetic acid to the hydrazino compound. 3) Ethyl thiosemicarbazonoformate was obtained by the reaction of thiosemicarbazide and ethyl orthoformate and this was led to 2-amino-1, 3, 4-thiadiazole and 3-mercapto-4, 1, 2-triazole.
By the respective condensation of 5-bromoquinoline with 6-, 7-, and 8-hydroxyquinoline, in the presence of copper dust, diquinoline 5, 6′-oxide (I), 5, 7′-oxide (II), and 5, 8′-oxide (III) were prepared. Condensation of 7-bromoquinoline and 5-hydroxyquinoline under the same reaction conditions afforded (II). A few derivatives of these diquinoline oxides were also prepared.
Aromatic aldehydes and their semicarbazones and thiosemicarbazones react with peptone or tryptophan, in hydrochloride acidity, to show violet, blue, or greenish coloration. This coloration was utilized in the microdetection of such compounds. To a minute amount of the sample or its ethanolic solution, approx. 10-20mg. of peptone or 2 drops of 1w/v% of tryptophan solution and 0.5cc. of conc. hydrochloric acid are added, and the mixture is heated in a water bath for 1-2 minutes. Limit of detection using peptone: 3 γ of p-dimethylaminobenzaldehyde.
As a different method for the synthesis of N1-acyl-4-aminonaphthalenesulfonamide, attempts were made on the condensation of 4-acetylaminonaphthalene sulfochloride and amidine hydrochloride, followed by the hydrolysis of the acetyl and imino radicals, and by the fusion ofthe sodium salt of 4-acetylaminonaphthalenesulfonamide and amidine hydrochloride, followed by the hydrolysis of acetyl and imino radicals.
Ultraviolet absorption spectrum of 20% parenteral solution of glucose was examined and market products were found to contain hydroxymethylfurfural (λmax 284mμ), a thermal decomposition product of glucose, and a substance with λmax 227mμ, which is chiefly formed by sterilization at 100°. Hydroxymethylfurfural is formed at a higher temperatures. The compound with maximum absorption at 227mμ was assumed to have the structure of >C=C-C=C< or >C=C-C=O.
By cyclization of methyl N-propionyl- or N-butyryl-anthranilate with metallic sodium in toluene solution according to Camps' synthetic method of 4-hydroxycarbostyril, a molecular compound (1:1 mole) of 3-methyl-4-hydroxycarbostyril and N-propionylanthranilic acid or 3-ethyl-4-hydroxycarbostyril and N-butyrylanthranilic acid was obtained as the main reaction product. From these molecular compounds, the 4-acetyl derivatives of the expected 3-alkyl-4-hydroxycarbostyril were separated in a good yield by boiling with acetic anhydride.
The effect of putrescine, cadaverine, γ-aminobutyric acid, and δ-aminovaleric acid on the production of streptomycin by Streptomyces griseus was examined and it was found that the highest production of streptomycin was witnessed by their addition in 10-5 molar concentration, as compared to the control without any addition (cf. Tables I to IV).