Data are presented for the unaerobic degradation of isoniazid (INAH) in aqueous solution at 37° over a pH range of 9.0 to 12.6 where nonionized INAH and INAH-anion co-exist. Preliminary work indicated that under aerobic condition, alkaline hydrolysis resulted in a mixture of isonicotinic acid (INA), isonicotinamide (INAA), 1, 2-disonicotinoylhydrazine (Bis), and small amounts of other unidentified products whereas under anaerobic condition INA and Bis were the principal products. When sequestering the trace amounts of heavy metal ions by EDTA, only INA was found as the degradation product and the sum of the molar concentration of INAH and INA in the solution was equal to the initial molar concentration of INAH in a given kinetic run. Under unaerobic condition, hydrolysis of INAH was found to be first order with respect to INAH. The overall rate of degradation of INAH as a function if pH can be described by the following equation. [numerical formula] A theoretical pH-rate profile calculated using the above equation is in good agreement with observed values. The heats of activation for the reaction of nonionized INAH and INAH-anion were found to be approximately 11 and 5.6 kcal./mole, respectively. The primary salt effect was observed in strong alkaline media. It was also found that hydrolysis rate of INAH was influenced by what appears to be general acid-base catalysis.

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Methyl 1-phthalimidomethyl-6-methoxy-3, 4-dihydroisoquinoline-3-carboxylate (IV) was obtained by a Bischler-Napieralski reactioh of methyl m-methoxy α-(phthalimidoacet-amido)hydrocinnamate (III), which was prapared by the condensation of 3-(m-methoxy-phenyl)-alanine. (I) with phthalimidoacetyl chloride followed by esterification. IV was catalytically hydrogenated to afford a 1, 2, 3, 4-tetrahydroisoquinoline derivative (V). Treatment of V with hydrazine hydrate and then with hydrochloric acid gave 8-methoxy-1, 2, 5, 6-tetrahydro-1, 5-imino-3-benzazocin-4(3H)-one(VI). Reduction of VI with lithium aluminum hydride afforded 8-methoxy-1, 2, 3, 4, 5, 6-hexahydro-1, 5-imino-3-benzazocine (VII). 3, 11-Dimethyl-8-methoxy-1, 2, 3, 4, 5, 6-hexahydro-1, 5-imino-3-benzazocine (VIII) was obtained by methylation of VII with methyl iodide in the presence of potassium carbonate. Finally, VII was acetylated with acetic anhydride and the product was reduced with lithium aluminum hydride to 3, 11-diethyl derivative (XI). A new example of N→N' acyl migration is presented. When 8-methoxy-11-acetyl-1, 2, 5, 6-tetrahydro-1, 5-imino-3-benzazocin-4(3H)-one (XII) was reduced with lithium aluminum hydride followed by acetylation, a normal product (XIV) and an N→N' acetyl-migrated product (XIV') were obtained.

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Examination was made on the colorimetric determination of Bi³⁺ using 3', 4', 5', 6'-tetrahydroxyfluoran, -tetrahydroxyfluoran-aminoacetic acid, and -hydroxyfluoran-imino-diacetic acid complexone as the coloring agent. The coloration became stable about 10 minutes after the addition of 3', 4', 5', 6'-hydroxyfluoran and about 2 minutes after the addition of hydroxyfluoran-complexone compounds, and the absorption constant for about 1 hour. Coloration of Bi³⁺ by 3', 4', 5', 6'-hydroxyfluoran derivative is effected at below pH 4, and the amount of methanol used to dissolve the hydroxyfluoran derivative dose not affect absorption in the quantity used for the determination. Effect of temperature at the time of coloration is small as long as it is below 50°. The absorptions of bismuth chelate of 3', 4', 5', 6'-hydroxyfluoran (λ_max 570 mμ), of hydroxyfluoran-aminoacetic acid complexone (λ_max 560 mμ), and of hydroxyfluoran-iminodiacetic acid complexone (λ_max 540 mμ) all follow the Lambert-Beer's law in the concentration range of 5 to 7 γ/ml, making it possible to use the absorption-concentration curve for quantitative determination. Presence of Zr⁴⁺ and Th⁴⁺ interferes in the determination of Bi³⁺ but the presence of other bivalent to tetravalent metal ions is almost without any effect.

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Examinations were made on the leaves, tree bark, and wood, treated separately, of Formosan Cryptocarya chinensis HEMSL. (Lauraceae) (Japanese name "Maruba-damo" ;Chinese name "Hou-Kou-kuei") and the bases listed in Table I were isolated in crystalline form. Base B (crychine) was obtained as its picrate of yellow prisms, m.p. 177°(sint. 162°), C₁₉H₁₇O₄N·C₆H₃O₇N. The free base, [α]¹⁵_D-220.2°(EtOH), UV : λ^EtOH_max 296.7 mμ, Its NMR spectrum (Fig. 1) indicated that it is a pavine-type new base possessing 4 aromatic protons, 2 methylenedioxy groups, and 1 N-methyl group. Treatment of crychine (IX) with phosphorous pentachloride gave an O-methyl compound (XII) through a phenolic base (XI). Base D (caryachine) occurs as colorless needles, m.p. 174∼175°, [α]²¹_D -269.6°(EtOH) C₁₉H__(19)O₄N. From its NMR spectrum (Fig. 2), this base was found to possess 4 aromatic protons, 1 methylenedioxy group, 1 methoxyl, and 1 N-methyl group; UV : λ^EtOH_max 291.5 mμ. The O-methylated compound of the phenolic base (XIII) obtained by cleavage of methylenedioxy group in O-methylcaryachine with phosphorous pentachloroide was found to agree with N-methylpavine (argemonine) (X) derived from papaverine (XIV). In other words, the structure of caryachine can be represented by formula (XVI). On the other hand, O-methylcaryachine agreed with the O-methyl compound if the phenolic base derived from crychine (IX) and it follows that the structure of crychine would be 13-methyl-2, 3 : 8, 9-dimethylenedioxy-5, 6, 11, 12-tetrahydro-5, 11-dibenzo[a, e]cyclooctene (IX). Base E, m.p, 241∼242°, was identified as dl-caryachine.

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A new glycoside was obtained, together with quercetin and taxifolin, from ceder (Chamaecyparis obtusa ENDL.) and was identified as taxifolin-3-glucoside.

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Reaction of phenols with alkyl aryl sulfoxide, in the presence of perchloric acid, progressed easily to afford alkyldiarylsulfonium perchlorate (I to VIII). Addition of phosphoryl chloride to perchloric acid facilitated the reaction of phenols with dialkyl sulfoxide to form dialkylarylsulfonium perchlorate (IX to XII). Heating of these sulfonium salts in hot, saturated potassium chloride solution easily afforded the corresponding diaryl sulfides (XIII to XX) and alkyl aryl sulfides (XXI to XXIV). This process is considered to be of value as a new method for introduction of various arylthio and alkylthio groups into phenols.

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2-Cyanoethyl phosphate employed as an efficient phosphorylating agent in the synthesis of nucleotide was found to be an excellent catalyst for the conversion of ribonucleosides to their 2', 3'-O-isopropylidene derivatives. This fact has led to the establishment of a novel, single-step conversion of ribonucleosides to 5'-ribonucleotides in a high yield using 2-cyanoethyl phosphate, acetone, pyridine, and dicyclohexylcarbodiimide without isolation of the 2', 3'-O-isopropylidene derivatives.

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Alkaloids occur in nature as various salts and mass spectra of these salts were found to appear in the form of their free base. In the present series of experiments, hydrochloride, hydrobromide, sulfate, phosphate, oxalate, malonate, succinate, tartrate, citrate, meconate, and picrate of codeine were prepared and their mass spectra were taken to measure the appearance temperature and the height of M⁺ ion peak. 1) Mass spectra of all the salts showed the spectrum of free codeine base and M⁺ ion peak was 299 m/e. 2) Relative intensity of the main fragment peak was the same in all the salts. 3) The temperature at which M⁺ ion peak appears increased in the order of the free base, malonate, hydrochloride, succinate, hydrobromide, tartrate, meconate, oxalate, picrate, phosphate, sulfate, and citrate. This order is considered to be related to volatility or sublimability of the acid radical. 4) The height of the M⁺ ion peak decreased in the order of (malonate), free base, succinate, tartrate, meconate, oxalate, citrate, phosphate, picrate, hydrochloride, hydrobromide, and sulfate. This order is considered to be related to the strength of the acid.

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Good results cannot be obtained by thin-layer chromatography of 8-hydroxyquinoline series compounds by ordinary silica gel plate due to excessive tailing. Relationship between the degree of such tailing and the stability of chelate compounds with metals, steric effect of the structure, and effect of co-ordination atoms was considered. A good result was obtained for prevention of tailing by treating the adsorbent with disodium ethylenediaminetetraacetate. Conditions for mutual separation of these compounds and method of their detection were also examined.

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N-Substituted compounds of 5-chloro-2-benzoxazolinone and 6-chloro-2H-1, 4-benzoxazin-3-ones were synthesized and their central nervous action was examined. Three of these compounds had muscle slackening action comparable to 5-chloro-2-benzoxazolinone. The sulfonamide derivatives of N-substituted compounds were synthesized and their diuretic action was examined. Six of these compounds had such action comparable to chlorothiazide.

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N-Substituted compounds of 5-chloro-2-benzoxazolinone and 6-chloro-2H-1, 4-benzoxazin-3-ones, substituted with halogen in 6- or 7-position, were synthesized and their antibacterial action was examined. Name of the N-alkylated compounds showed any antibacterial activity but some of the N-chloro derivatives showed a marked activity.

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Examinations were made on the position of sulfonamide and halogen substituted in 5-chloro-2-benzoxazolinone and 6-chloro-2H-1, 4-benzoxazin-3-ones, and it was found that these were substituted in 6-position in the 5-chloro compound and in 7-position in the 6-chloro compound.

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In order to study the interaction of soluble protein of bovine lens and phenoxazone compounds, examinations were made on α- and β-crystallin solution added with phenoxazone compounds, using the precipitation-titration method with light-scattering photometer. Examination of the effect of concentration of protein solution on the light-scattering curve showed that 0.2% of the phenoxazone compound added to α-crystallin solution and 0.001% added to β-crystallin solution were the optimal concentration, and that completely desalted protein solution must be used. Further examinations were made on the addition of 14 kinds of compounds, including phenoxazone compounds and quinone derivatives, and it was found that the addition of pyrido-phenoxazone compound resulted in the decrease of first maximum at pH 5.5 of the light-scattering curve in the direction of 45° and 90° in α-crystallin. The degree of this decrease varied with the concentration of the additive but no change was seen in the scattered light in the direction of 135° and transmitted light in the direction of 0°. In the case of β-crystallin, entirely no effect was found with phenoxazone and other compounds.

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1) 6-Iodo-8-nitroquinoline (V) was synthesized from 2-nitro-4-iodoaniline by the Skraup reaction and reduced with stannous chloride and hydrochloric acid to the amino compound (VI). These amino compounds (VI, VII, VIII) and m-iodoaniline were thiocyanated by treatment with ammonium thiocyanate and bromine in acetic acid. These thiocyanates (IX to XII), 5-thiocyanato-8-aminoquinoline, and p-thiocyanatoaniline were diazotized and reacted with phenol or m-halophenol in weakly alkaline or neutral reaction to form the azo compounds (XII to XIX). On the other hand, compounds XXV and XXVI were synthesized from I and II by the application of p-toluenesulfonyl chloride in pyridine, and XXVII and XVII by the application of acetic anhydride to III and IV. 2) Synthesis of 5-thiocyanato-6-chloro-8-hydroxyquinoline was attempted by the diazotization of 6-chloro-8-aminoquinoline to XXI and its thiocyanation with ammonium thiocyanate and bromine in acetic acid or with calcium thiocyanate in acetic acid but XXI was recovered. Consequently, XXI was nitrated in the cold to the nitro compound (XXII), reduced with Raney nickel and hydrazine to the amino compound (XXIII), and submitted to the Sandmeyer reaction to obtain XXIV. Antifungal activities of these synthesized compounds against Candida and Trichophyton were tested.

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Pharmacological tests were carried out on 10 kinds of commonly used tonic crude drugs (rehmannia radix, lycium cortex, bupleurum radix, ligusticum radix, cnidium rhizome, ginseng radix, panax rhizome, longana fruit, cassia cortex, and dioscorea radix) on following points using mice. (1) Action on forced swimming time, (2) action on acute liver injury caused by carbon tetrachloride, (3) growth of the animals in long-term administration of the crude drug, (4) effect on sexual cycle by lone-term administration of the crude drug and repeated administration of carbon tetrachloride, and (5) variation in death rate from repeated administration of carbon tetrachloride udder a long-term administration of the crude drug. Good results, with little inhibition of a growth curve, were obtained with ginseng, rehmania, cnidium, followed by panax and cassia, poor result was obtained with ligusticum and dioscorea. However, some of the crude drugs showed a good result, without side effects, if given in a certain form and in a certain dose.

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By the use of the Magnus method with an isolated hind gut of the crayfish, an experimental approach to the correlation between acetylcholine (ACh) and 4-aminobutyric acid (GABA) derivatives concerning receptor systems was presented. From its results, such structurally related compounds as GABA, 3-hydroxy-4-aminobutyric acid (GABOB), and monosodium glutamate have antagonistic activities to ACh-induced contracture, and these antagonistic mechanisms seemed to be almost similar to each other. Further, the potencies of antagonism to ACh decreased in the order of GABA≥monosodium glutamate>GABOB.

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Various types of acetylcholine (ACh) and 4-aminobutyric acid (GABA) actions against excised hind gut of crayfish were examined by the graphic method by which the nature of 1st and 2nd receptor systems was clarified. Graphic analysis on the behavior of Na⁺ showed that the 1st receptor was not dependent on Na⁺ but the 2nd receptor was strongly dependent on it. Decrease in the level of Ca²⁺ increased the contractile responses to ACh and eradicated the anti-ACh action of GABA. These phenomena may be due to depletion of Ca²⁺ from the site of receptor membrane by decreasing the level of Ca²⁺ in the medium or pretreatment of the gut sample with picrotoxin. On the other hand, pretreatment of the sample with 4-guanidinobutyric acid gave results similar to that with picrotoxin but there seems to be a considerable difference in the mechanism of action of these two substances.

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L-3-Hydroxykynurenine was isolated in a pure crystalline form from the larvae of a mutant strain "aka-aka" of silk worm. The body fluid of this mutant strain was very useful for a large scale preparation of L-3-hydroxykynurenine yielding 69 g. from 150, 000 larvae.

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Hemolytic action of polyoxyethylene carboxylates was studied. The hemolytic activities of these surface-active agents increased with the increase in the length of alkyl chains, the ethylene oxide chains being kept constant, and decreased with increasing length of the ethylene oxide chains provided that the alkyl chains are the same. The release of cholesterol from the red cell membrane prior to complete hemolysis was detected by means of a thin layer chromatography. The mechanism of hemolysis was briefly discussed on the basis of these findings.

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Following earlier reports on the reduction of hypoepistephanine (I) and epistephanine (II) by Tomita and Watanabe, ^{1, 2)} reduction of II with zinc dust in dil. sulfuric acid was carried out. From the isolation of diastereomeric dihydroepistephanine-A (IV-A) and dihydroepistephanine-B (IV-B) as its product, the reduction was found to progress in two directions, as was the case with hypoepistephanine (I).

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