Several cataractogenic compounds were studied, especially quinone compounds in detail, for their inhibitory action on active transport in rabbit lens surviving in vitro. 1, 4-Benzoquinone, 1, 2-naphthoquinone and vitamin K₃ inhibited cation transport and glycolysis in the lens, whereas coenzyme Q₇ did not. Hydroquinone and β-naphthol, the reduced form of 1, 4-benzoquinone and 1, 2-naphthoquinone, scarcely affected cation transport and glycolysis. Among the reducing substances found in the lens, ascorbic acid showed potent antagonistic action against 1, 4-benzoquinone. CySH competed with 1, 2-naphthoquinone slightly. GSH competed with 1, 2-naphthoquinone certainly and with the other quinone compounds in less degree. 2, 4-Dinitrophenol inhibited cation transport, but did not inhibit glycolysis. Alloxan had no effect on both responses.

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Chlorination of benzene with various catalysts was examined and the formation of dichloro compound was followed by recrystallization and gas-chromatographic determination. The most suitable catalyst was found to be a mixture of iron, sulfur, and lead oxide. Chlorination of benzene using this catalyst was examined on a pilot-plant scale and p-dichlorobenzene was found to be formed in a maximum yield of approximately 70%.

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Intraperitoneal injection of 35 mg/kg of pentobarbital was given to cats, and sleeping time was measured, taking the time required from the disappearance of eyelid-closure reflex until its recovery as the index. The animals were divided into six groups given the pretreatment 1, 3, 7, 14, 21, and 28 times, and the control group, Drug metabolizing enzymes in the liver microsomes of the cats in the treated groups were examined by measuring periodicallies the activities of aminopyrine N-demethylase, aniline hydroxylase, and pentobarbital metabolizing enzyme. At the same time, accumulations of pentobarbital in the plasma, cerebral cortex, cerebral medulla, heart, liver, kidney, fat, and skeletal muscle in the cats were measured to examine their correlation. It was thereby found that the drug-metabolizing enzyme activities increase for about 2 weeks after continuous administration of pentobarbital, then decrease slightly. There were correlation between enzyme activities and sleeping time, and with the amount of pentobarbital accumulated in each organ.

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Effect of continuous administration of aminopyrine, sulpyrine, and their mixture (high and low doses) on drug metabolizing enzyme activities in liver microsomes was examined. The enzyme activities examined were morphine N-demethylase, aminopyrine N-demethylase, and aniline hydroxylase, and male Wistar rats were used. At the same time, effect of long term administration of these drugs on rat body weight and pathohistological examination of the liver were also observed. Body weight increase was considerably inhibited after 40 days, compared to that of the control, and this tendency was especially marked in the high dosage group. Activities of drug metabolizing enzymes in liver microsomes varied with characteristic wave form, though this differed somewhat according to the substrate. Difference between high and low dosages was observed during the initial period after the start of the administration. There was no difference in these activities according to aminopyrine, sulpyrine, and their mixture. Pathohistological observations of the liver revealed no marked change.

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Biotin was synthesized by a new method conveniently. 1, 4-Butylenedimagnesium halide was prepared satisfactorily from 1, 4-dihalogenobutane with magnesium powder in ether-toluene in the presence of magnesium bromide. Treatment of 3, 4-(1', 3'-dibenzyl-2'-oxoimidazolido)-2-oxothiophane (IV) with 1, 4-butylenedimagnesium halide in toluene at -30--50°, and then with carbon dioxide afforded hydroxy-dibenzylbiotin (VII) in a good yield. Effect of reaction temperature, amount of magnesium bromide, and mole ratio of bifunctional Grignard reagent to IV were examined. VII was dehydrated to 2 -(4-carboxybutylidene)thiophane derivative (X) by refluxing in acetic acid. Hydrogenation of X with Ni-silica im methanol gave dibenzylbiotinmethylester (XI). dl-Biotin was obtained by the treatment of XI with 47% hydrobromic acid.

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Synthesis of dimethyl 3, 4-dihydroxy-2, 5-furandicarboxylate (I) was examined. Hydrolysis of I gave a new compound, 3, 4-dihydroxy-2, 5-furandicarboxylic acid. Alkylation and acylation of I afforded a dozen of new compounds. It was found that hydrolysis of I, dimethyl 3, 4-bis(5-methyl-2-furoyloxy)-2, 5-furandicarboxylate, and dimethyl 3, 4-bis(5-nitro-2-furoyloxy)-2, 5-furandicarboxylate respectively afforded the decomposition products, 2-furoic acid, 3, 4-dihydroxy-2-carboxy-5-carbomethoxyfuran, dimethyl 3, 4-dihydroxy-2, 5-furandicarboxylate, and 5-methyl-2-furoic acid. Hydrolysis of dimethyl 3, 4-dibenzyloxy-2, 5-furandicarboxylate gave 3, 4-dibenzyloxy-2, 5-furandicarboxylic acid.

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2-[(5-Methoxycarbonyl-2-furyl)vinyl]benzenes were synthesized by the Wittig reaction of 5-methoxycarbonyl-2-furfuryl triphenyl phosphonium chloride and various benzaldehydes or ketones. In the synthesis of 2-[(5-methoxycarbonyl-2-furyl)-1-(5-nitro-2-furyl)vinyl]benzene, two sudstances of mp 146-147° and of mp 155-157°, assumed to be stereoisomers, were obtained. These substances formed the corresponding stereoisomers during the process of hydrolysis, chlorination with thionyl chloride, and amination. The determination of cis or trans forms of these isomers was made through ultraviolet absorption and nuclear magnetic resonance spectra.

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Bromination of 2-[2-(5-nitro-2-furyl)vinyl]benzothiazole gave 2-[1-bromo-2-(5-nitro-2-furyl)vinyl]benzothiazole which was dehydrohalogenated with dimethylformamide and potassium hydroxide to obtain 2-[2-(5-nitro-2-furyl)ethynyl]benzothiazole. The usual method of using methanol and potassium hydroxide in this case afforded 2-[2-methoxy-2-(5-nito-2-furyl)vinyl]benzothiazole.

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Syntheses of methyl 2-(5-substituted-furoyl)amino-5-methoxycarbonyl-4-thiazolylacetate and methyl 2-(5-substituted-furoyl)amino-5-methoxycarbonyl-4-oxazolylacetate were attempted to react methyl 2-amino-5-methoxycarbonyl-4-thiazolylacetate (A) and methyl 2-amino-5-methoxycarbonyl-4-oxazolylacetate (B) with 5-substituted-furoyl chloride respectively. However, in the reaction of B with 5-substituted furoyl chloride, except the case of 5-nitrofuroyl chloride, a certain compound, which is supposed to be di-acyl derivative, was obtained and their chemical structures were studied. Furthermore, hydrolysis of methyl 2-(5-substituted-furoyl)amino-5-methoxycarbonyl-4-thiazolylacetate and ester exchange reaction of methyl 2-(5-nitro-furoyl)amino-5-methoxycarbonyl-4-oxazolylacetate were studied.

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5-Nitro-2-furoyl chloride, 5-bromo-2-furoyl chloride, 2-furoyl chloride, and 5-methyl-2-furoyl chloride were each reacted with non-acylating compounds like monosubstituted benzenes, thiophene, and furan in carbon disulfite, using titanium tetrachloride as a catalyst, to make comparative examination of their reactivity from the yield of their products. It was thereby found that the reactivity approximately decreased in the order of methyl, bromine, hydrogen, and nitro group when these replaced the 5-position.

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Two structures (VIa and VIb) are possible for the condensation product of 2-amino-6-ethoxybenzothiazole (I) with β-bromopropionic acid or its ethyl ester. In order to establish the structure of this condensation product, it was dehydrogenated and the resulting dehydro compound was compared directly with the compound (XIVb) obtained by condensation of (I) with diethyl ethoxymethylenemalonate. These two compounds are not identical and consequently the dehydro compound must have structure (XIVa) making it highly probable that the structure of the original condensation product coresponds to (VIa). This deduction was proved by showing that (VIa) is identical with 3, 4-dihydro-8-ethoxy-2H-pyrimido [2, 1-b] benzothiazol-2-one which was synthesized independently by condensation of p-phenetidine with ethyl β-bromopropionate followed by treatment with ammonium thiocyanate and hydrochloric acid with the subsequent cyclization of the resulting intermediate (XXV) in the presence of bromine in chloroform.

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Condensation of resacetophenone (III) and 2 -, 3-, or 4-pyridinecarboxaldehydes (IV, V, VI) in the presence of alkali afforded, though in a low yield, the corresponding 2', 4'-dihydroxy-2-, 3-, or 4-azachalcones (VII, VIII, IX). The use of 4'-(benzyloxy)-2'-hydroxyacetophenone (X) instead of III in the reaction with IV to VI afforded the corresponding 4'-(benzyloxy)-2'-hydroxy-2-, 3-, or 4-azachalcones (XI, XII, XIII) in a comparatively good yield. Heating of XI to XIII with conc. hydrochloric acid in glacial acetic acid resulted in facile debenzylation and the corresponding dihydroxy derivatives (VII, VIII, IX) were obtained. The 4'-hydroxyl group in these dihydroxy derivatives was assumed to be forming a salt with the nitrogen atom in the pyridine ring from the examination of their infrared spectra.

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3-Pyridylacrylophenones were synthesized in a good yield by the condensation of benzoylacetic acid with pyridinecarboxaldehydes in the presence of piperidine. They were also prepared by heating α-(ethoxycarbonyl)azachalcones, which are the condensation products of ethyl benzoylacetate and pyridinecarboxaldehydes, with 40% sulfuric acid or concentrated hydrochloric acid.

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Isomerization of 2', 4'-dihydroxy-2-, -3-, and-4-azachalcones (I, II, and III) and 4'-(benzyloxy)-2'-hydroxy-2-and-3-azachalcones (IV and V) was studied under acid- or basecatalyzed condition. Under acidic condition, 2- and 4-azachalcones (I, IV, III) were cyclized to 3(2H)-benzofuranone derivatives (VI, IX, VIII), and 3-azachalcones (II, V) were cyclized to chromanone derivatives (VII, X). Under basic condition, I to V were all isomerized to the corresponding chromanones (XI, VII, XII, XIII, and X).

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The intraperitoneal administration of 0.15M Nacl, 0.15M KCl or Ringer-phosphate-bicarbonate solution in a dose of 0.1 ml/day/mouse for 10 days stimulated the growth of solid Ehrlich tumor, in the order : NaCl, KCl and Ringer-phosphate-bicarbonate. The antitumor effects of some hydrochloromethiazides on solid Ehrlich tumor disappeared when Ringer-phosphate-bicarbonate solution was used in lieu of physiological saline as solvent, for the antitumor test of these compounds.

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Examinations were made on the potency test method for chemical radio-protectors using the life-prolongation effect on X-irradiated mice as the indicator. Standards used for this test were AET and MEA. Male ddY mice were irradiated with 600-900 R of X-rays and the animals were observed for the next 90 days to find optimal conditions for the potency tests.1) When the survival rate of irradiated mice is to be used as the indicator for potency tests of radio-protectors, the mice should be irradiated with a dose of X-rays (700-900 R) by which all the control mice will be dead about 2 weeks after the irradiation and the survival rate of the mice in experimental group should be measured at the time when the survival rate of the control mice becomes 0%. 2) When the survival time of irradiated mice is to be used as the indicator for potency tests of radio-protectors, the mice should be irradiated with a dose of X-rays (700-800 R) by which the mean survival time of the control mice becomes about 10 days, mean survival time of the experimental group is measured 30 days after the irradiation, and protective potency is calculated by comparison of the mean survival time with that of the control group. 3) Comparison of the minimum effective does of AET and MEA indicated that there is a difference in the molar potency of the two compounds and AET was found to be 2-8 times stronger than MEA.

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The so-called 'trans-ylidation' was carried out using ethoxycarbonylmethylenetriphenylphosphorane (I) as the phosphorane, and p-toluenesulfonyl chloride (IIa), benzenesulfonyl chloride (IIb), p-chlorobenzenesu1fonyl chloride (IIc), and p-acetamidobenzenesulfonyl chloride (IId) as the halogenides, in dry benzene at room temperature. In this case, the corresponding sulfones (IIIa-d) were not obtained and the corresponding compounds formed by the reduction (deoxygenation) of the sulfones were obtained in the form of α-(p-tolylthio)-(Xa), α-phenylthio (Xb), α-(p-chlorophenylthio)-(Xc), and α-(p-acetamidophenylthio)ethoxycarbonylmethylenetriphenylphosphoranes (Xd). The Wittig reaction of these compounds with 5-nitro-2-furfural (XIa), 3-(5-nitro-2-furyl)acrolein (XIb), and p-nitrobenzaldehyde (XIII) was carried out and the foregoing products were proved form the corresponding products of this reaction.

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We describe a new method of synthesis of 2-alkyl-2, 3-dihydro-4-pyrones (X) by cyclization of 1, 1, 5-trialkoxy-3-alkanone (IV). (IV) was synthesized from 1-chloro-1, 4-alkadien-3-one (III) with alcohols. By oxidation of 2, 3-dihydro-2-methyl-4-pyrone (Xa), 3-hydroxy-2-methyl-4-pyrone (maltol) (I) was obtained.

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A new furoquinoline alkaloid, pteleine³⁾, was synthesized by the same route as the synthesis of previously reported furoquinoline alkaloids, i.e. dihydrodictamnine, dihydroevolitrine, kokusaginine, maculine, dihydroskimianine, and 7-hydroxy-8-methoxydihydrodictamnine, Condensation of 5-methoxy-2-nitrobenzoyl chloride and α-acetyl-γ-butyrolactone, in the presence of magnesium, gave 2-(5-methoxy-2-nitrobenzoyl)-γ-butyrolactone and catalytic reduction of its enol-methyl ether, obtained by treatment with diazomethane, afforded 2, 3-dihydropteleine. Bromination of 2, 3-dihydropteleine with N-bromosuccinimide and subsequent dehydrobromination gave pteleine.

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An examination was made on Perkin reaction between thiophene aldehydes and p-nitrophenylacetic acid and it was found that 5-nitrothiophene aldehyde which possess nitro group at α-position in thiophene nucleus reacted normally, according to Perkin reaction. However, the one which possess nitro group at other than α-position, reacted according to Perkin reaction, besides bis(p-nitrobenzyl)ketone was formed by the reaction of p-nitrophenyl acetic acid molecules each other.

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Reaction series in the synthesis of thiolactone (XI) from acetoxy compound (IV) in Goldberg's biotin synthesis were examined. IV underwent reaction with hydrogen sulfide and hydrogen chloride in isopropanol to afford 5-isopropoxy-2-thiophanone derivative (VII). Treatment of VII with potassium hydrogen sulfide gave mercapto compound (IX) and disulfide of IX (X). Refluxing of IX in acetic acid or reduction of X with zinc powder in acetic acid lead to formation of XI, however total yield of XI from IV was low. A new satisfactory synthesis of XI was found. Treatment of IV with hydrogen sulfide and hydrogen chloride in dioxane afforded 5-hydroxy-, and 5-chloro-2-thiophanone derivatives (VI and XV) with a good yield. Reduction of VI or especially of XV with zinc powder in acetic acid gave XI with a high yield.

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An examination was made with Grignard-reaction of thiolactone (I). Treatment of I with 3-ethoxypropylmagnesium bromide in benzene gave only 2-hydroxy-2-(3-ethoxypropyl)thiophane derivative (II), while lactone (III) gave 2-hydroxy-2-(3-ethoxypropyl) tetrahydrofuran derivative (IV) and glycol (V). Reaction of both I and butylmagnesium bromide afforded 2-hydroxythiophane derivative (VIII) as a by-product, which was produced by the reduction with Grignard-reagent caused by the steric hinderance of I. According to the several step treatments, the condensation product of I with 3-methoxyprop-1-yne-magnesium bromide was led to the formation of thiophanium bromide (IX). dl-Biotin was prepared obtained from the condensation product of I with 4-benzyloxybutylmagnesium chloride by the modified method.

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Surface and transfer anesthetic activities of 3-substituted 2-benzoxazolinone and 2-substituted 2-thiobenzoxazole have been standardized, employing the usual method with a slight modification. In the surface anesthetic activities, the former compound was shown to be stronger than the latter, and as to the transfer anesthetic activities, the activities are generally reverse. Among them, the strongest was shown to be 2.71 of lidocaine in surface anesthetic activities and 4.09 of procaine in transfer anesthetic activities.

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Ether and methanol extracts of the crude drug, (Pulsatilla cernua SPRENG.), were examined, and stigmasterol and β-sitosterol were obtained as the neutral substance from the ether extract. The methanol extract was submitted to hydrolysis and hederagenin, oleanolic acid, and a minute quantity of acetyloleanolic acid were obtained as the acid substance.

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The 1-position of 5-methyl-3-pyrazolidinone, which was synthesized by the cyclization of ethyl crotonate and hydrazine, was halogenated and then it was reacted with amines to give 1-alkylaminoacyl-5-methyl-3-pyrazolidinone derivatives. These compounds synthesized did not show any superior analgetic activities to aminopyrine.

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The reactions of potassium phthalimide with Grignard reagents which give 3-hydroxy-3-alkylphthalimidine or 3-alkylidenephthalimidine, are described. The formations of the two products are controlled by treatment of the reaction mixture either with aq. NH₄Cl-NH₃ or with aq.HCl. The structures of the products were decided by spectral data.

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According to Waldi's description, ketoses on TLC chromatogram, are coloured yellow by spraying anthrone-acetic acid-phosphoric acid reagent and heating them at about 110° for 5-6 minutes. The authors found that this colour reaction was not specific for ketoses as shown in Table I. When the chromatogram was heated at 60° for 10-25 minutes after spraying the same reagent, yellow colour was developed from fructose and sucrose, but no colour appeared from rhamnose, aldopentoses and aldohexoses. Phosphoric and acetic acid were essential for this reagent. Replacing glacial acetic acid by acetic anhydrid, the colour changed brownish yellow, but the limit of detection was not changed. The limit of detection is as follows : Fructose 1 μg; sucrose 5 μg. This reaction can be used for PPC chromatogram also.

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