Various substituent groups were introduced into 3, 5- or 3, 4-positions of 1-phenyl-6(1H)-pyridazinone ring and their condensation to 1-phenylpyrazolonecarboxylic acid by treatment with alkali hydroxide or hydrobromic acid was examined. It was found that 3, 4-substituted derivatives do not undergo condensation but 3, 5-substituted derivatives were found to undergo rearrangement to 1-phenyl-3-hydroxy-5-pyrazolecarboxylic acid if the starting compounds and reaction conditions were so chosen to form the expected intermediates 1-phenyl-3, 5-dihydroxy-6(1H)-pyridazinone (B) and 1-phenyl-2-methyl-5-hydroxy-3, 6(1H, 2H)-pyridazinedione (C).

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To confirm the carbon skeleton of photosantoninic acid, to which the structure (I) was suggested in the previous paper, selenium dehydrogenation was carried out on a reduction product of the ketonos of I, but this reaction failed to give any aromatic compounds, probably owing to an undesirable pyrolytic cleavage of the cyclopropanes for aromatization. Therefore, dihydrolumisantonin (II), having a moiety of the structure (I), was chosen as a model compound and methods for the conversion of its bicyclo[3. 1. 0]hexan-2-one ring into a cyclohexanone were studied. It was found that prolonged boiling of the 1.5N aqueous potassium hydroxide solution of II produced a hydration product (IXa). The structure and the stereochemistry of IXa were discussed.

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According to the model experiment reported in the previous paper, photosantoninic acid (I) was reacted with boiling aqueous alkali but only formed an unidentified resinous product. However, when this reaction was carried out in the presence of zinc dust, I afforded two crystalline products, C₃₀H₄₂O₇ and C₃₀H₄₆O₈, depending on reaction conditions. The former, for which the structure (II) was proposed, was formed under mild condition. The latter, to which the structure (VII) was suggested, was obtained by prolonged treatment of I or II with 1.5N sodium hydroxide solution and zinc dust. A probable mechanism of the formation of VII from II is shown in Chart 2. Selenium dehydrogenation of the catalytic hydrogenation product of VII afforded none of binaphthalene derivative but only 2-ethyl-5-methylnaphthalene, resulting from a pyrolytic scission of the carbon-carbon bond linking two decalin skeletons of VII.

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Preliminary experiments revealed that (2-bromo-4, 5-dimethoxyphenyl) acetic acid hydrazide possessed an anti-cancer action. Therefore, various hydrazide derivatives were synthesized and their anti-cancer action was examined. None of the compounds synthesized, i.e. 2-halogeno-4, 5-dialkoxybenzoic acid hydrazide, (2-halogeno-4, 5-dialkoxyphenyl) acetic acid hydrazide, 2-halogeno-4, 5-dialkoxyhydrocinnamic acid hydrazide, and their related compounds, showed any better effect than 6-mercaptopurine.

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Condensation products of (2-bromo-4, 5-dimethoxyphenyl) acetic acid hydrazide and various carbonyl compounds were prepared and their anti-cancer activity was examined. Some anti-cancer effect was observed in the condensation product with isovanillin. The reaction of the above hydrazide with chloral or bromal in alcohol was found to result in dehydrazino reaction to form ethyl (2-bromo-4, 5-dimethoxyphenyl) acetate. The mechanism of this reaction is now being examined.

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Bromination of (3, 4-dimethoxyphenyl) acetic acid hydrazide was found to form, besides various compounds, 1, 2-bis [(2-bromo-4, 5-dimethoxyphenyl)acetyl] hydrazine.

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Compounds with nitro group in place of bromine in (2-bromo-4, 5-dimethoxyphenyl)-acetic acid hydrazide and related compounds were synthesized and their anti-cancer activity was examined. 5, 6-Dimethoxy- and 5, 6-methylenedioxy-oxindole, and 6, 7-dimethoxycarbostyril were found to have some anti-cancer effect against Ehrlich solid tumor by subcutaneous inoculation.

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Bei einem Versuch zur Herstellung von L-N, N-Diäthylphenylalaninol- und D, L-N, N-Diäthylhomophenylalaninol-p-aminobenzoesäureester führte eine Hochdrukreduktion von 3-Acetamido-4-phenyl-2-butanon mittels Paney-Ni nur zu Homophenylalaninol.
Anschließend wurden eine Umlagerung des vom Homophenylalaninol abgeleiteten 1-(p-Nitrobenzoyl)-2-benzyl-3-methylaziridins (II) mittels Erhitzung in N-(α-Methylcinnamyl)-4-nitrobenzamid (III) sowie eine Umlagerung diess Verbindung III mittels konz. Schwefel-säure in 2-(p-Nitrophenyl)-4-methyl-5-benzyl-2-oxazolin (IV) versucht. Das Ultrarotes Spektrum der Verbindung III zeigt ein charakteristisches Band bei 960cm^-1 und sie stells eine Trans-Form.

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6-Chlorocoumarin-³⁶Cl was synthesized by the modified diazotization from 6-amino-coumarin hydrochloride-³⁶Cl. Diazotization was carried out with sodium nitrite and 3N hydrochloric acid in ether or with isoamyl nitrite in dioxane. The diazonium chloride-³⁶Cl formed was decomposed in ether (with addition of hydrogen chloride gas) or with copper powder in acetone.
Oral administration of this 6-chlorocoumarin-³⁶Cl to a rabbit resulted in decrease of urine on the 2nd and 3rd day but the amount of urine returned to normal on the 4th day. Radioactivity decreased progressively irrespective of the urinary amount and 22.8% of the original radioactivity was found in the urine excreted during 96 hours after the administration.
A part of 6-chlorocoumarin-³⁶Cl is distributed in various organs and the incorporation ratio per gram of the organ decreases in the order of (excreta), small intestine, kidneys, pancreas, spleen, skeletal muscles, heart, bladder, and brain. Incorporation ratio to total weight of organs decreased in the order of kidneys, pancreas, liver, heart, spleen, and brain.

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1) Heme protein was extracted from the water-soluble substance of hog ascaris muscle by ammonium sulfate fractionation but the presence of cytochrome c was not found. This negative result may be due to the small amount contained and not detected by this method. Hemoglobin-like substance was obtained in a fairly large amount by the extraction method.
2) The ascaris was thought to carry out semi-anaerobic energy metabolism in the host's intestinal tract and the normal motion of the ascaris was observed in the glass U-shaped tube in which the air was replaced with nitrogen. It was found that the ascaris showed motor excitation, convulsion, and paralysis due to kainic acid and dihydrokainic acid.

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A quantitative examination was made on tetracycline (I) epimerization in the digestive tract and its influence on absorption. I undergoes a reversible epimerization at 4-carbon to form 4-epi-tetracycline (II). The epimerization occurs in the pH range of ca. 3-6 and its rate is increased by the presence of certain anions, such as a citrate, phosphate, or acetate. Other adjuvants usually incorporated in preparations of I, such as glucosamine hydrochloride, have very little effect on the epimerization rate whereas calcium ion markedly decreases it. Oral administration of I with or without citric acid or of II indicated that no detectable amount of II is excreted in the urine from a rat or humans although the intestinal content from the rat clearly demonstrated the presence of II. Absorption experiments from the rat stomach and small intestine were carried out using pre-equilibrated solutions of pH 4, 5, and 6. The result indicates that little absorption of I and II occurs from the stomach and that I is more rapidly absorbed than II from the small intestine. For example, the degrees of 90-minute absorption of I and II at pH 5 are 13% and 0.2%, respectively. Considering all the evidences presented here, it is concluded that epimerization in the digestive tract is one of the reasons to be accounted for the relatively low recovery of I in the urine.

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A new method was found for the estimation of N⁴-glucuronides of sulfapyridine in the reaction mixture of sulfapyridine with the rat liver homogenate. The mechanisms of the N⁴-glucuronide formation in vitro from sulfapyridine and the boiled extract of the liver (UDPGA) was examined with rat liver homogenate, it was concluded that self apyridine N⁴-glucosiduronate was not formed by the action of the liver enzyme in vitro, but was formed non-enzymatically.

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Extraction of bilirubin with hydrochloric acid from the crude drug, oriental bezoar, obtained from the gall bladder of cattles, was examined. A suitable concentration of hydrochloric acid for the extraction was 5-10% and 7.5% hydrochloric acid was used. The content of bilirubin in oriental bezoar was measured by Heilmeyer-Krebs' method. A concretion from Australia had the highest concentration of bilirubin among the several kinds examined.

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To examine the membrane permeability of ions, collodion membrane was prepared and used as the membrane electrode to carry out potentiometric titration of the systems of aniline sulfate-barium chloride, aniline hydrochloride-silver nitrate, and phenylenediamine hydrochloride-silver nitrate. As previously mentioned, the collodion membrane selects and transfers anions when the above-mentioned organic amines are titrated with inorganic electrolytes, although it usually transfers cations. The electric potential of the system of phenylenediamine was twice as large as that of aniline. A collodion membrane, dipped one hour previously in aniline sulfate solution, was used after being dried. As the drying time was made longer, the electric potential was found to become larger. A collodion membrane, dipped two days previously in aniline sulfate solution, was used for the potassium sulfate-barium chloride system. The membrane obviously showed anion selectivity and this property was still maintained after one month in water.
It was assumed that the collodion membrane combined with these organic amines through Van der Waals' forces which rose when a part of the benzene ring of these compounds contacted the membrane and that consequently the membrane acquired anion selectivity.

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5-O-Benzoyl-1, 2-O-isopropylidene-D-xylofuranose was oxidized with di-tert-butyl ether-chromium trioxide to 3-oxo-5-O-benzoyl-1, 2-O-isopropylidene-D-xylofuranose, which was reduced catalytically over Adams platinum in tert-butanol and 5-O-benzoyl-1, 2-O-isopropylidene-D-ribofurane was obtained stereospecifically. Its hydrolysis by the conventional method afforded D-ribopyranose.

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1. The fresh rhizomes of Anemarrhena asphodeloides BUNGE collected in July were found to contain sarsasapogenin and markogenin, as previously reported by Takeda, et al., and also one more sapogenin, neogitogenin (m.p. 253-254°, [α]_D¹⁹-66.4° (c=0.24, CHCl₃); diacetate, m.p. 215-219°, [α]_D¹⁸-112° (c=0.41, CHCl₃)).
2) A commercial crude drung“Timo” (the dried and stored rhizomes of A. asphodeloides BGE.) contained sarsasapogenin, and six steroid saponins were detected in its methanol extract. They were respectively named timosaponin A-I, A-II, A-III, A-IV, B-I, and B-II. A-III was isolated as colorless prisms, m.p. 317-322° (decomp.), [α]_D²⁷-41.6° (c=0.27, dioxane) and B-I as amorphous powder, m.p. 170-180°.
3. Timosaponin A-III was composed of sarsasapogenin, D-glucose, and D-galactose, and the sugar moiety was presumed to be a biosc. B-I and A-I were regarded, respectively, as a parent saponin having another mole of glucose, and the prosapogenin, of A-III.

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Two kinds of flavonol, yellow needles and pale yellow prisms or needles, were obtained from the methanolic extract of the tree bark of pecan (Carya pecan ENGL. et GRAEBN.). The flavonol forming yellow needles was recrystallized from hydrous methanol into yellow needles, m.p. 317-320°, C₁₆H₁₂O₇⋅H₂O (acetate, m.p. 197-198°). It has one methoxyl group and potash fusion afforded protocatechuic acid and phloroglucinol. Its decomposition with 50% potassium hydroxide also afforded protocatechuic acid and phloroglucinol monomethyl ether. Methylation with dimethyl sulfate gave quercetin pentamethyl ether and demethylation with hydriodic acid (sp. g. 1.7) gave quercetin. It was easily methylated by diazomethane to form quercetin pentamethyl ether. It showed strong fluorescence by ultraviolet irradiation. From these experimental results, this flavonol was considered to be quercetin monomethyl ether, with methoxyl in 5-position. Quercetin 5-methyl ether had been found in nature and named azaleatin, and the present flavonol from pecan was found to agree well with azaleatin.

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A series of 3-(N-tert-aminoalkylpropionamido) thiophenes, which are the isomers of 2-(N-tert-aminoalkylpropionamido) thiophenes, were synthesized.
2-{N-[2-(N-Methylphenethylamino) propyi] propionamido} thiazole and 2 (or 4)-{N-[2-(N-methylphenethylamino) propyl] propionamido} pyridine were also synthesized. Analgesic action of these compounds was examined and some of them showed the activity approximately equal to that of codeine.

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5-Methyl-4, 5, 6, 7-tetrahydrothiazolo [4, 5-c] pyridin-2(1H)-one (III) was prepared by the interaction of 1-methyl-3-bromo-4-piperidine and ethyl xanthamidate, and its analgesic action was estimated to be about 40% of that of aminopyrine.

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