Dehydrogenation of epistephanine (I), isolated from Stephania japonica MIERS (Japanese name "Hasunoha-kazura"), with mercury acetate and ethylenediaminetetraacetic acid (EDTA) was examined. Epistephanine is converted by this reagent into dehydroepiste-phanine (X)(Table I). Catalytic reduction of X over palladium-carbon in sodium hydroxide alkalinity converts it to dl-epistephanine (XI) whose reduction with sodium borohydride in methanol results in stereospecific hydrogenation, giving optically inactive dl-dihydroepistephanine-B (XII-B). Reduction of XI with zinc dust in dil. sulfuric acid results in progress of the reaction in two directions, yielding dl-dihydroepistephanine-A (XII-A) and XII-B. These facts agree well with reduction of optically active epistephanine (I) by sodium borohydride in methanol and by zinc dust in dil. sulfuric acid. Treatment of X with sodium borohydride in methanol directly produces optically inactive dl-dihydroepistephanine-B (XII-B).

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Examinations were made on the effects of initial concentration of riboflavin (C₀), hydrogen ion concentration[H⁺], and ionic strength (μ) on light fading of riboflavin solution and it was found that the fading progressed according to the following formu1a : [numerical formula] where A and B are constants, and k_C, k_H, and k_μ are apparent light-fading rate constants relative to initial concentration of riboflavin, hydrogen ion concentration, and ionic strength, respectively.

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3-(5-Nitro-2-furyl) acryloyl azide (III) was synthesized by diazotization of 3-(5-nitro-2-furyl) acrylic acid hydrazide (I) or by treating 3-(5-nitro-2-furyl) acryloyl chloride (II) with sodium azide. III reacts with esters of amino acids, aliphatic aminis, and pyimidinyl-hydrazines at rooom temperature yielding the corresponding amides and hydrazides. Refluxing of N-[3-(5-nitro-2-furyl) acryloyl] glycine ethyl ester (IVa) with phosphorus pentachloride in dry chloroform give 2-[2-[5-nitro-2-furyl) vinyl]-5-ethoxy-1, 3-oxazole (V). Schiff bases can be obtained by treating 1-phenyl-2-amino-1, 3-propanediols or 4-phenyl-5-amino-1, 3-dioxanes with 5-nitro-2-furaldehyde. Reduction of D- and L-2, 2-dimethyl-4-phenyl-5-(5-nitro-2-furfurylidene) amino-1, 3-dioxanes [XVa (α) and XVb (α)] with sodium borohydride to D- and L-2, 2-dimethyl-4-phenyl-5-(5-nitro-2-furfuryl) amino-1, 3-dioxanes was carried out readily. Antimicrobial activities of these nitrofuran compounds are presented in Table VI.

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In order to clarify the mechanism of rectal absorption of sulfa drugs from fatty oils, this absorption was examined by perfusion of rat rectum with fatty oils of different nature, using higher fatty acids, their esters, and higher alcohols. Absorption rate of sulfisoxazole becomes greater as the drug in the fatty oil becomes more easily liberated into the excretion fluid. Absorption rate of sulfapyridine is not affected greatly by the nature of fatty oils, while that of sulfathiazole becomes smaller with fatty oils from which the drug is more easily liberated into the excretion fluid. These results seem to indicate that drug absorption from fatty oils takes two different processes ; that of absorption through the rectal membrane after being liberated into the excretion fluid and that absorbed directly from the fatty oil through the rectal membrane.

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Acetylsalicylic acid, which undergoes decomposition by acid-base catalyzed reaction, was mixed in powdered state with buffer salts of various pH and it was found that decomposition at a definite temperature and humidity was dependent on the pH of the buffer salts to be mixed, as is the case in a solution. Decompositions of acetylsalicylic acid in buffer agents was found to follow the pseudo-first order reaction after a lag period. Reaction rate constants in the atmosphere of saturated potassium nitrate solution at 30, 35, 40, and 45°were measured and the values were found to be dependent on temperature. Arrhenius plots gave almost the straight line. However, this plots deviate from straight line if phase variation occurred within the range of reaction temperature. The apparent activation energy of this reactions calculated from the slope of the straight line was a value larger than that of the reaction in solution.

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The electrokinetic potential (ζ-potential) of sulfisoxazole, sulfadimethoxine, and N¹-acetylsulfisoxazole in aqueous solution and in 10% sucrose solution was measured by the streaming potential method and the influence of sodium lauryl sulfate (SLS) and polyoxyethylene nonyl phenyl ether (PE-N) on the electrokinetic potential of these sulfanilamides was investigated. It was thereby recognized that ζ-potential was negative and its absolute value increased markedly with the increase of SLS concentration, and it had a maximum value at 4×10^-3 mole/L. of SLS concentration. This is considered to be due to adsorption of SLS on sulfanilamide. The amount of adsorbed SLS was calculated according to the following equation : [numerical formula] where Δσ is the difference between the charge densities of the surface in the solutions, with and without SLS. It was found that the absorption of SLS on sulfanilamide is a Langmuir type. On the other hand, the absolute value of the negative ζ-potential of sulfanilamides decreased by addition of PE-N, although PE-N is a nonionic surface-active agent.

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Trichloroethyl phoshate is a hypnotic and this is hydrolyzed rapidly by phosphatases in the body. This paper deals with the results of an investigation on hydrolysis of trichloroethyl phosphate in vitro and the recoveries of trochloroethanol and trichloroethyl phosphate from biological materials. Hydrolysis was carried out in 0.1N HCl, 0.1N NaOH, or 0.1M formate buffer (pH 4.0) at 100°, and with calf intestinal alkaline phosphomonoesterase at 37°. The reaction using the phosphomonoesterase gave the best result in the hydrolysis of trichloroethyl phosphate. Trichloroethanol was found most stable under this condition. Recoveries of trichloroethanol and trichloroethyl phosphate added to human blood plasma and to an artificial gastric content were almost quantitative. In these experiments, amount of trichloroethanol was estimated by the method of Lieberman and Hindman.

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In continuation of the previous work, ^*1 examinations were made for non-phenolic bases in the tree bark and wood of Cryptocarya chinensis HEMSL.(Japanese name "Maruba-damo, " Chinese name "Houkou-kuei"). d-O-Methylcaryachine (III) was isolated from the tree bark and crychine (I) from the wood (cf. Table I). Examination of basic components in the wood of Cryptocarya konishii HAYATA (Japanese name "Konishi-gusu", Chinese name "Tu-nan") revealed the presence of L-(-)-N-norarmepavine, dl-N-norarmepavine, and dl-coclaurine (cf. Table II). Although these two plants belong to the same Cryptocarya sp., there is a difference in the bases they contain, and the results of the present investigation is very interesting from chemotaxonomical point in that Crypt. konishii contains the same base as the plants of Machilus spp.

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Methyl 2-bromo-3-oxoglutarate (III) was prepared from methyl 3-oxoglutarate (II), and various nucleophilic reagents were reacted with active bromine atom in α-position of III to obtain isoxazole derivatives (IV∼VI), 2-aminooxazole derivatives (VII∼XI), 2-amino-thiazole derivatives (XII∼XV), and 2-anilinooxazole derivatives (XVI∼XVIII).

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Anti-saliva Parotin-A serum was obtained after the administration of saliva Parotin-A (SPA) to intact rabbits in the following doses : 10 μg./kg. for 10 days, 100 μg./kg. on the 11th day, 1 mg. on the 42nd day, and 2 mg. on the 54th day. By the technique of Ouchterlony, the antiserum obtained showed a precipitin band against SPA, but was not reactive to Parotin, S-Parotin, α-Uroparotin, β-Uroparotin, lyophylized saliva, etc., showing immunological specificity of the antiserum. The quantitative precipitin tests indicated that 1 ml. of the antiserum corresponded to 300 μg. of SPA. Administration of SPA mixed with the antiserum was found to be as effective as SPA alone upon the circulating leucocytes, while the antiserum itself showed no significant influence upon them. After mixing SPA with the antiserum in a ratio which ensured complete precipitation of SPA, the precipitate as well as the supernatant showed leucocyte-promoting activitiy. Besides this activity, the precipitate reduced the circulating lymphocytes, while the supernatant increased the granulocytes more markedly. These results suggest that the SPA used in this study contained at least two components ; one was precipitated by the antiserum and, after precipitation, still retained its leucocyte-promoting activity and the other was not precipitated. It was also found that the antigenic center of SPA would be different from the leucocyte-promoting activity in the molecules.

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Reaction of 3, 6-dimethoxy-4-nitropyridazine 1-oxide (I) with acetyl or benzoyl chloride gives 1-acetoxy (or benzoyloxy)-3-methoxy-4-chloro-6 (1H)-pyridazinone (II or IV). It was found that in this reaction, 3, 6-dimethoxy-4-chloropyridazine 1-oxide (VI) is formed as an intermediate which reacts with acetyl chloride to form II. Oxidation of V with acetic acid and hydrogen peroxide gave VI, VIII, and IX. Methoxylation of VI with sodium methoxide gave a product which agree with VII obtained by methoxylation of I. This fact proved that VI is 3, 6-dimethoxy-4-chloropyridazine 1-oxide. Separation of VIII by thin-layer chromatography and measurement of its ultraviolet spectrum showed that it is 3, 6-dimethoxy-5-chloropyridazine 1-oxide, an isomer of VI.

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In the hydrated derivatives of glucuroic acid glucuronamide monohydrate, potassium glucuronate dihydrate, and sodium glucuronate isoniazone dihydrate, water of hydration present has different properties. These hydrates were submitted to the measurement of changes in weight, dielectric constant, and differential heat, activation energy of dehydration, and specific surface area by the BET method. The result of these measurements threw doubt on whether water of hydration in one mole of potassium glucuronate dihydrate and two moles on sodium glucuronate isoniazone dihydrate could be strictly called water of crystallization in its limited sense. Even if such water of hydration could be included in the scope of the water of crystallization, such water will be a problem in the manufacture of pharmaceutical preparations.

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Water of hydration contained in glucuronamide, potassium glucuronate, and sodium glucuronate isoniazone has different nature. In order to comparatively examine their nature, specific polarization of water (P_w) was calculated from the measurement of apparent dielectric constant (ε'_a) at the time of adsorption isotherm, from the enthalpy of evaporation and standard entropy by measurement of dissociation water vapor pressure. Infrared spectra and X-ray diffraction of the hydrated and anhydrate compounds were also measured. It was thereby found that water in these hydrates dose not show correlation between the quantity of adsorption and specific surface area, such as in seen in silica gel. Consequently, water of hydration in these compounds is not an adsorbed water but a stable water of crystallization in glucuronamide, while that in the other two compounds is a water of crystallization in a limited sense although their water of hydration is labile due to reversibility of adsorption and desorption.

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The separatory determination of phenacetine in some pharmaceutical formulae was examined utilizing coloration with sodium 1, 2-naphthoquinone-4-sulfonate. The sample containing about 100 mg. of phenacetine was hydrolyzed by refluxing with 2 ml. of concentrated hydrochloric acid for 40 minutes. When cooled, the solution was transfered to a 200 ml. measuring flask, diluted to the mark with water, and mixed thoroughly. This solution was diluted farther with 5 volumes of water. To 2 ml. aliquot of this solution in Squibb's separatory funnel, 2 ml. of 2% potassium hydrogenphthalate and 0.7 ml. of 1% sodium 1, 2-napathoquinone-4-sulfonate were added, the mixture was shaken for 3 minutes, and cooled on crushed ice for 3 minutes. Then the solution was extracted with 10 ml. of chloroform by shaking for 3 minutes. The extract was dried over anhydrous sodium sulfate in stoppered test tube. After 10 minutes, absorbance of the chloroform solution was measured at 485 mμ. The results obtained by this method are shown in Tables I and II.

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The volume fractions of each component at the plait point, (v₁)_pl, (v₂)_pl, and (v₃)_pl, were calculated according to Scott's theoretical equation, in the ternary system, solvent-1, nonsolvent-2 and polymer-3, as the function of interaction parameters A, B, and C. From these calculations, the relative volume of nonsolvent to be added to the system (V/V₀)_pl before the precipitation starts and the initial concentration of polymer (v₃)⁰ were calculated for the polymerization degree P=100, 250, 500, 1000, 2500, 5000, 10000, and ∞, and for various values of A, B, and C. From these results it has been concluded that the selection of a solvent and nonsolvent to be used for the fractional precipitation of a polymer should take into consideration the parameter B which is responsible for the interaction between the solvent and the nonsolvent, because the parameter B also affects the precipitation condition of the polymer, although the parameter B itself is not related explicitly to the interaction with the polymer molecules.

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Mannich reaction was carried out with the use of substituted hydroxylamines and 3, 3"-(substituted benzyloximino)-4', 4"-bis (substituted) propiophenones (Table I), 3-(N-sub-stituted benzyloxy-substituted benzylamino)-4'-(substituted) propiophenones or 3-(N-alkoxy-alkylamino)-4'-(substituted) propiophenones (Table II), 3-(2-isoxazolidinyl)-4'-(substituted)-propiophenone, and 3-(tetrahydro-2H-1, 2-oxazin-2-yl)-4'-(substituted) propiophenone, (Table III) were synthesized. Substituted hydroxylamines used included O-substituted and O, N-disubstituted hydroxylamines, isoxazolidines, and tetrahydro-1, 2-isoxazine, and substituted acetophenone was used for the active methylene compound. Some of the compounds formed by this reaction were reduced with sodium borohydride and some α-[2-(substituted benzyloxy-substituted benzylamino) ethyl]-(para-substituted) benzyl alcohols and α-[2-(tetrahydro-2H-1, 2-oxazin-2-yl) ethyl]-(para-substituted) benzyl alcohols (Table IV) were obtained.

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It was found that 2-[2-(5-nitro-2-furyl) vinyl]-5-amino-1, 3, 4-oxadiazole (II) is obtained by the reaction of thiosemicarbazide with 3-(5-nitro-2-furyl) acryloyl chloride in excess pyridine and by refluxing 5-nitro-2-furanacrylic acid hydrazide with potassium thiocyanate in aqueous hydrochloric acid. 2, 2-Disubstituted 3-acetyl-5-[2-(5-nitro-2-furyl) vinyl]-1, 3, 4-oxadiazolines (VIa∼c) were prepared by refluxing alkanone 5-nitro-2-furanacrylic acid hydrazones with acetic anhydride. Antimicrobial activities of these nitrofuran compounds are presented in Table III.

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