Polarography of 16 phenylsulfonyl derivatives having vinyl, ethyl, or 2-chloroethyl group attached directly to SO₂ group was carried out vs. mercury pool in benzene-methanol (3 : 2, v/v) solution using tetrabutylammonium iodide (0.08M) as a supporting electrolyte. The reduction waves observed with these compounds were classified into three types ; waves due to vinyl group (W_V), to phenylsulfonyl group (W_P), and to p-substituted halogen (W_X). Both W_V and W_P seemed to be irreversible, and the half-wave reduction potential (E_1/2) of the former was found to be ca. -1.5 V (two-electron reduction), while that of the latter was ca. -1.4--1.9V. W_X appeared at the most positive potential among the three reduction waves. Some discussions were made on the relationship between the structure and E_1/2.

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The extent of hydrolysis of milk casein by the semi-alkaline proteinase from Aspergillus melleus was compared with that by α-chymotrypsin, trypsin, pepsin, etc. The data obtained indicated that 65% of the milk casein was hydrolyzed by the semi-alkaline proteinase (100 units casein). This value was about 4.5 times greater than that by α-chymotrypsin. Milk casein hydrolyzed with the above animal proteinases was further hydrolyzed by the semi-alkaline proteinase. On the contrary, animal proteinases reacted slightly with milk casein hydrolyzed by the semi-alkaline proteinase. These results suggest that the semi-alkaline proteinase was better as a digestive enzyme.

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Unlike α-acyl-3, 5-dimethoxyphenylacetonitriles, α-acyl-m-methoxyphenylacetonitriles (Ia, b, c, and d) gave 4-amino-5-arylpyrimidines (IIa, b, c, and d) and m-methoxyphenylacetonitrile (III) on being heated with H₂NCHO and POCl₃. In the case of α-benzoyl-m-methoxyphenylacetonitrile (Id), β-amino-α-(m-methoxyphenyl)cinnamonitrile (IV), the intermediate of pyrimidine synthesis, and benzamide (V) were also isolated. III or IV gave IIa or IId under more drastic conditions. Like III, 3, 5-dimethoxyphenylacetonitrile (VI) gave 4-amino-5-arylpyrimidine (VII) by analogous treatment.

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Glucuronic acid (GH) was found to undergo coloring by hydroxamic acid and the degradation of ethyl glucuronate (GE) was re-examined by this method. The reaction scheme proposed in a previous (in the preceding paper), [chemical formula], was confirmed, where GL is glucuronic acid lactone. Further, in a weakly acid solution, hydrolysis of ethyl glucuronate proceeded according to the reaction schem [chemical formula]where G- is a glucuronate ion. Effect of pH and buffer concentration on the rate constants was examined and the following equations were obtained : [numerical formula]

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Strychnine and brucine were extracted from slices of strychni seeds, cut into various sizes (#1-#4), in water at 27, 37, and 47°. Results of analysis of extraction rate showed that the mechanism of extraction consists of washing, diffusion, and capillary extraction, but the capillary extraction occupies a small part. Mass transfer coefficients of these three mechanisms, which depend distinctly on temperature of the solvent, were determined.

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The upper ground portion of Cynanchum boerhavifolium H. et A. (Asclepiadaceae), obtained by the scientific expedition to Patagonia by the Hokkaido University team in 1966, were proved to contain about 0.9% of glycoside mixture. Acid hydrolysis of this glycoside mixture gave β-amyrin, lineolon, isolineolon, isoramanone, benzoylisolineolon, and two unidentified crystals.

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Neutral components of the alcoholic extracts from Pachysandra terminalis SIEB. et ZUCC. (Buxaceae) were submitted to alkaline hydrolysis and systematic examination was made on the benzene-soluble part of the neutral fraction thus obtained. Several kinds of sterols, friedelin-type triterpenes, and cycloartenol-type triterpenes were isolated in crystalline form and characterised.

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Crude saikosides are crude saponin fraction extracted from Bupleurum falcatum L. Anti-inflammatory and other pharmacological actions of this fraction are described. Crude saikosides showed a potent local irritation by topical application, but a significant decrease in dextran-induced edema of the rat paw, and increased capillary permeability in the mouse peritoneal cavity and in croton-induced granuloma pouch of the rat by the oral route. On the contrary, it did not show any inhibiting effect on carrageenin-induced edema, acetic acid-induced edema, adjuvant arthritis, and experimental liver fibrosis of the rat. In addition, it had no protective effect on histamine shock of the guinea pig and anaphylactic shock of the mouse. Crude saikosides did not affect gastric motility, but it was significantly effective in the prevention of the stress ulcer of the rat. Crude saikosides showed a strong stimulating effect in the intestinal propulsion test of the mouse. It markedly potentiated the contraction of isolated guinea pig ileum induced by acetylcholine, but not by histamine. Furthermore, crude saikosides showed a transient hypotensive action and a decrease of heart rate in the dog.

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With the object of examining the π-acceptor property of carcinogenic 4-nitroquinoline 1-oxide, spectrophotometric examination was made on the interaction of the N-oxide compound with a variety of methyl substituted benzenes and anline derivatives. The following results were obtained through analysis of the new absorption bands which appeared in the visible difference spectra of mixed systems of the above derivatives and the N-oxide compound : (1) Absorption maxima of the difference bands shifted toward a longer wavelength region with increasing polarity of the solvents. (2) There was a linear relationship between I_P values of the methyl substituted benzenes and aniline derivatives and hv values of the absorption maxima. (3) It was confirmed that complexes of 1 : 1 molar ratio were formed by the interaction. (4) A corresponding relationship was found to exist between K values of the methyl substituted benzene-N-oxide compound complexes and I_P values of the substituted benzenes. (5) The K values of the aniline derivative-N-oxide compound complexes were affected markedly by the steric effect of substitutent methyl groups. (6) Analysis of the pH effect indicated that the uonionized species of aniline derivatives were more favorable for the interaction. Based upon these results (1-6), it was presumed that π-π type and n-π type charge transfers were involved in the interaction of 4 -nitroquinoline 1-oxide with methyl substituted benzenes and aniline derivatives. The magnitude of ΔH values was consistent with this presumption. It was also found that the carcinogenic quinoline compound is a stronger π-acceptor than non-carcinogenic 4-nitropyridine 1-oxide.

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Berberine was extracted from slices of Berberis thunbergii, cut into various sizes (#1-#4), with water and methanol at 37°. Results of analysis of extraction rate, indicated that the mechanism of extraction consists of washing, diffusion, and capillary extraction, and mass transfer coefficients for each mechanism were determined. Comparing with the extraction of berberine from the cortex of phellodendron, ³⁾ mass transfer coefficients were distinctly larger.

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Twenty-nine N-phenylanthranilic acid derivatives were synthesized and their oral effectiveness on carrageenin-edema and cotton pellet-granuloma in rats, or UV-induced erythema in guinea pigs was tested. Intravenous acute toxicity of these compounds on mice was also examined. Anti-edema activity of N-phenylanthranilic acid (PA) was estimated to be almost equal to that of salicylic acid. N-(α-Naphthyl)anthranilic acid was more potent but showed higher acute toxicity than did PA or phenylbutazone. Methyl or chlorine substitution of PA enhanced both anti-inflammatory and toxic activities of the compounds, while carboxyl group, as well as amino or hydroxyl, considerably reduced these biological properties. Of the compounds tested, Flufenamic acid was the most active in all the three antiinflammatory assays. The derivatives related to Flufenamic acid were also active agents. However, no enhancement of toxicity was noted by trifluoromethyl substitution in PA and further no significant reduction of biological activities was observed by introduction of another carboxyl group to fulfenamic acid molecule, contrary to the case of methyl and chlorine substituted derivatives of PA. As an exception, it was found that four inactive compounds displayed relatively high toxicity on mice. In general, the biological activities did not varid with substituted position, but were markedly affected by the kind of substituent present.

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The Wittig reagent (Ph₃P=C-R¹-R²) was reacted with 5-nitro-2-furyl isocyanate with R²=H and R¹=CN, COOC₂H₅, COC₆H₄Br(p), COC₆H₅, COCH₃, reacted with 2-(5-nitro-2-furyl)vinyl isocyanate with R²=H and R¹=CN, COOC₂H₅, reacted with 2-furyl isocyanate with R³=H and R¹=CN, COOC₂H₅, COC₆H₅Br(p), COC₆H₅, COCH₃, and 12 kinds of corresponding carbamoylmethylenetriphenylphosphoranes were newly synthesized. From the IR and NMR spectral measurements of these products, compounds obtained from these reactions with the exception of those reacted with the Wittig reagent with R¹=CN, all had a strong tendency to form intramolecular hydrogen bonding. 2-Furoyl thioisocyanate was also reacted with the Wittig reagent, with R²=H and R¹=CN and COOC₂H₅, and two kinds of corresponding thiocarbamoylmethylene triphenylphosphoranes were synthesized. Of these products, those obtained from reaction with the Wittig reagent with R¹=COOC₂H₅ showed a marked formation of intramolecular hydrogen bonding.

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Color reactions of coriose (D-altro-3-heptulose) (I) and D-manno-3-heptulose (II) in the test tube and on the filter paper, as summarized in Tables I and II, are common to these two 3-heptuloses, and significantly differ from that of other monosaccharides. The absorption maxima of the colored solutions are also in agreement with the above observations. The Rf values of I and II on paper-partition chromatography by the ascending method using five kinds of developing solvent mixtures are shown in Table III. The gas-liquid chromatography of coriose shows that the initial trimethylsilyl ether produced immediately on the addition of the reagent mixture is converted in the presence of excess reagent mixture into two other products of longer retention time. This two-step trimethylsilylation is useful for the detection and identification of coriose by gas chromatography since coriose-containing syrup also shows transformation of peaks including these three peaks. D-manno-3-Heptulose shows slow transformation of the initial trimethylsilyl ether into the mixture of final products which exhibit three peaks on gas chromatogram. These transformations of the trimethylsilyl ethers of 3-heptuloses are retarded when trimethylsilylation is done at lower temperature, or with limited amount of the reagent. Gas chromatography of trimethylsilyl ethers of three heptitols, volemitol (V), D-glycero-D-altro-heptitol (VI), and perseitol (VII) was also carried out.

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Binding of pentobarbital (sodium 5-ethyl 5-(1-methylbutyl)barbiturate) with plasma protein of male and female rats was studied in vivo using the modified Rehberg's method. The female rat had more extensive binding capacity than the male rat, but the fraction of drug bound was similar in both sexes. As a result of castration, the degree of sex difference in the binding capacity lowered. When SKF -525 A, the inhibitor of metabolism of pentobarbital, was preadministered to the rat, blood level and amount bound of pentobarbital remained at the highest level, but fraction of drug bound was constant. The extent of binding was lowered in the rat pretreated with ether.

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In continuation of the previous report on (Ia), its 2'-methyl (Ib) and 4'-chloro (Ic) derivatives were synthesized (Table I) and submitted to pharmacological screening. As shown in Table II, toxicity of Ib was greater than that of Ia while Ic had less toxicity. In general, introduction of a methyl or chlorine atom resulted in the increase of central depressive properties and other pharmacological actions remained the same as those of Ia or slightly weaker. The pressor action noted in the preceding report was weaker in all the compounds synthesized in the present series ecxept in No. 39.

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Ultraviolet irradiation of 5, 5-dimethyl-3, 7-dioxocyclooctanecarbonyl azide cyclic bis (ethylene acetal) (5) and cycloheptanecarbonyl azide yielded a β-lactam, 6 (5, 5-dimethyl-9-azabicyclo[6.2.0]decane-3, 7, 10-trione cyclic 3, 7-bis(ethylene acetal)), and a γ-lactam, 12(7-azabicyclo[4.2.1]nonan-8-one), respectively. The latter represents a novel azabicyclic ring system. No lactams were obtained from cyclohexanecarbonyl, cyclopentanecarbonyl, and pivaloyl azides.

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2-Amino-3-cyano-4, 5-bis [2-furyl] furan (I), obtained from furoin and malononitrile, was reacted with carbon disulfide, formamide, and iminoethers, and 2-ethoxymethyleneamino-3-cyano-4, 5-bis (2-furyl) furan (III), obtained from the reaction of I and ethyl orthoformate, was reacted with ammonia and hydrazine to obtain the corresponding difurylfuro[2, 3-d] pyrimidines. 3-Amino-4-iminofuro[2, 3-d]-3, 4H-pyrimidine (XII) underwent rearrangement to 4-hydrazinodifurylfuro[2, 3-d] pyrimidine (XIII) on being heated. Reaction of XII and XIII with ethyl orthoformate or acetic anydride afforded the corresponding furo[3, 2-d]-s-triazolo[2, 3-d] pyrimidines (XIV and XV) and furo[3, 2-d] -s-triazolo[4, 3-c]pyrimidines (XVI and XVII). Heating of XVI and XVII in pyrimidine effected their rearrangement to XIV and XV.

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Separative determination of α-chymotrypsin and Bromelain, frequently used as an anti -inflammatory enzyme preparation, was examined. p-Chloromercuribenzoic acid (PCMB) was used as the inhibitor of Bromelain. Since Bromelain activity in preparations was completely inhibited by 10^-4_M of PCMB in the reaction system, remaining α-chymotrypsin activity was determined with good accuracy. The difference between their total activity and α-chymotrypsin activity agreed with Bromelain activity.

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Wittig reaction was carried out under usual reaction conditions on sulfur-containing complex ylides, α-(para-substituted phenylthio)ethoxycarbonyl-(III), -cyano-(V), -benzoyl-(VII), and-furoylmethylenetriphenylphosphoranes (IX), with 5-nitro-2-furfural (XI). It was found that, of these complex ylides, IIIa-d and Va-d afforded the corresponding vinyl thioethers. With IIIa-d, reaction was carried out on p-nitrobenzaldehyde (XVIII) and 5-nitro-2-thiophenecarboxaldehyde (XXIII), and the corresponding vinyl thioether compounds were obtained. Each of these thioethers was separated into two kinds of stereoisomers, and their steric configuration was determined from their IR and NMR spectra. The vinyl thioethers were oxidized with hydrogen peroxide to the corresponding vinyl sulfones.

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The absorption and distribution of ³H-labeled local anesthetic, 2-methyl-2-n-propylamino-o-propionotoluidide hydrochloride(³H-LA-012), were examined by means of wholebody autoradiography of mice after its application to various mucous membranes. When ³H-LA-012 was administered rectally, the drug was more rapidly absorved, and the highest levels of radioactivity were found in the liver and kidney 10 minutes after the administration. The accumulation of radioactivity was greater after administration to the rectum than to the baccal cavity, vagina, glans penis, and the conjunctival cul-de-sac. At three hours, the level of radioactivity in various organs decreased markedly whereas radioactivity in the gastrointestinal contents increased. The radioactivity was observed slightly in various organs 30 minutes after applying the drug on the glans penis, increased gradually until 3 hours, and disappeared 6 hours after the administration. When ³H-LA-012 was instilled into the conjunctival cul-de-sac, the drug was found to be systemically distributed through the lacrimal duct, esophagus, and alimintary canel, and that the distribution pattern of the radioactivity was similar to that after administration to the vaccal cavity, vagina, and the glans penis.

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Ethyl 2-pyridineacetate (IVa) reacts easily with the Vilsmeier reagent to form ethyl α-(dimethylaminomethylene)-2-pyridineacetate (Va) in 50% yield. Similarly, 2-pyridineacetonitrile (IVb), ethyl 2-quinolineacetate (VIa), and 2-quinolineacetonitrile (VIb) undergo the Vilsmeier reaction to form the corresponding enamines, α-(dimethylaminomethylene)-2-pyridineacetonitrile (Vb), ethyl α-(dimethylaminomethylene)-2-quinolineacetate (VIIa), and α-(dimethylaminomethylene)-2-quinolineacetonitrile (VIIb). Va reacts with ketene to form ethyl 4-oxo-4H-quinolizine-1-carboxylate (XII : R=CO₂Et), and with diketene to form ethyl 3-acetyl-4-oxo-4H-quinolizine-1-carboxylate (XVa). Similarly, enamines Vb, VIIa, and VIIb react with diketene to form 3-acetyl-4-oxo-4H-quinolizine-1-carbonitrile (XVb), ethyl 2-acetyl-1-oxo-1H-benzo[c]quinolizine-4-carboxylate (XVIIIa), and its 4-nitrile isomer (XVIIIb). XVa can also be obtained from Va and ethyl acetoacetate, and its reduction with sodium borohydride gives its alcohol derivative (XVII).

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Possible protective effect of 5-hydroxytryptophan against radiation damage was examined in vitro, using the ascites tumor type Furth's mastcytoma cells which have the ability to synthesize 5-hydroxytryptamine and Ehrlich ascites tumor cells not having such ability. Protective effect was judged by the amount of 5-hydroxyindole excreted in 24-hour urine of the host mice, (C57L×A)F₁ female, in the case of Furth mastcytoma cells, and the body weight increase rate in ddN male mice in the case of Ehrlich ascites cells after transplantation of the cultured cells. Observations were made 8-10 days after transplantation of the cells. X-Ray irradiation of the cells was made in a dose of 1000 R, and the number of cells transplanted was 4×10⁶ cells/0.5 ml in the case of Furth cells and 20×10⁶ cells/0.5 ml in the case of Ehrlich cells. Protective effect of 5-hydroxytryptophan was seen in the case of Furth cells in a dose of 1 mole/25000 cells but not in the case of Ehrlich ascites tumor cells.

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The root tissue culture of Panax ginseng C.A. MEYER was found to require 2, 4-dichloro-phenoxyacetic acid as the essential component. The growth of the callus was the best when modified White's medium was supplemented with 10% of coconut milk, 0.1 ppm of 2, 4-dichlorophenoxyacetic acid, and 0.1 ppm of gibberellin.

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