The liquid ammonia-metallic sodium cleavage reaction of methoxy substituted diphenyl oxide & dibenzo-para-dioxin derivatives have been discussed with respect to the molecular parameters estimated from the modified Hueckel Molecular Orbital treatments, and favorable correspondences have been acknowledged among empirical and theoretical evidences.

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The actions of hexylguanidine on the smooth muscle preparations were compared with those of cocaine using guinea-pig hypogastric nerve-vas deferens, trachea, rat stomach, intestine and perfused rabbit ear preparations and the following results were obtained. In each preparation, the responses induced by the electrical stimulation of the nerve were suppressed with hexylguanidine (10^-3-10^-5M). On the other hand, the responses were suppressed with a high dose of cocaine (>10^-5M), but were potentiated with a low dose (10^-6M). In the smooth muscle preparations, giunea-pig vas deferens and perfused rabbit ear preparations which produced the contraction by catecholamines such as norepinephrine and epinephrine, the actions of catecholamines were potentiated by hexylgunidine and cocaine. On the other hand, on the smooth muscle preparations, guinea-pig trachea and rat stomach preparations, which produced the dilation by catecholamines, the actions of catecholamines were unaffected by hexylguanidine and cocaine. On the guinea-pig intestine, the contractions induced by tryptamine and 5-hydroxytryptamine were suppressed by hexylguanidine and cocaine, but those induced by acetylcholine were not affected. From the results mentioned above, it is considered that the action of hexylguanidine may be neurotropic and the action is almost similar to the action of cocaine.

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The actions of hexylguanidine sulfate (HG) on the cardiovascular system and blood glucose were investigated using blood pressure in spinal cat, guinea-pig heart tissue, rabbit heart and perfused ear. And the following results were obtained. In spinal cats, HG (5 mg/kg, i.v.) produces a rise in blood pressure of about 60 mmHg. The pressor actions are not affected by hexamethonium, by adrenalectomy and by pretreatment with reserpine, but are suppressed by phentolamine and by cocaine. Moreover, HG potentiates the pressor action of norepinephrine and inhibits those of tyramine, guanethidine and ephedrine. On the perfused rabbit ear, also, HG (10^-5g/ml) potentiates the vasoconstriction induced by epinephrine and suppresses that induced by tyramine. However, high concentration of HG (10^-4g/ml) produces vasodilation. The contractions of isolated guinea-pig atria and isolated rabbit papillary muscle are slightly decreased by HG. From the results mentioned above, it is considered that the pressor action of HG is due to a direct sympathomimetic action on the α-adrenergic receptors, but part of its action is connected with catecholamine stores in the adrenergic nerves or with some other perpheral site except the adrenal medulla. Furthermore, HG raises the blood glucose concentration of rabbit and potentiates the hyperglycaemic action by epinephrine.

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2, 3-Disubstituted 6-nitroquinoxalines were reacted with potassium cyanide in alcoholic solutions to form 2, 3-disubstituted 6-alkoxyquinoxaline-5-carbonitriles (I, III and IV) and 2, 3-disubstituted-5-aminoisoxazolo [4, 3-f] quinoxalines (II and V) at the yield of about 50 and 30%, respectively. The reaction of 2, 4-dinitroaniline with potassium cyanide in methanolic solution gave o-methoxybenzonitrile compounds (VII and VIII). The same reaction was carried out in the presence of potassium ferricyanide and only dinitro-benzonitrile (VI) was obtained. Each VI and VII were reduced catalytically to o-phenyl-enediamine compounds and then condensed with benzil to yield the corresponding quinoxaline compounds. These were identical with the direct alkoxycyanation products of 2, 3-disubstituted 6-nitroquinoxaline.

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Reaction of aromatic N-oxide with enol ether in the presence of benzoyl chloride was examined. 2-Ethoxycyclohexene (II) reacted readily with quinoline 1-oxides (I, IV) and isoquinoline 2-oxide (VI), producing α-2-cyclohexanonyl derivatives (III, V, VII) in fairly good yields. Similarly, the reaction of I with 2-ethoxypropene (IX), methyl vinyl ether (XI) and dihydropyrane (XIV) gave 2-acetonyl-(X), 2-(2-methoxyvinyl)-(XII) and 2-(5-dihydropyranyl)-quinolines (XV), respectively. Nucleophilic reactivity of enol ether in this reaction was considerably lower compared with that of enamine ; no satisfactory result was obtained with II and pyridine 1-oxide and also with I and furan, thiophene and anisole under similar conditions.

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Several discussions have been extended on JC-H, a²_H and △X of alkyl derivatives with respect to the substituent constants σ_i and σ_π, and showed that they were all linear with σ_i-0.2σ_π. This result, which is also accepted similarly in ¹H chemical shift, suggests that the state of hybridization of carbon atom is the dominant factor in determining the variation of JC-H.

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The present paper deals with a new method to determine a required HLB of oil and an adaptability of surfactants to oils. Measurements were made of a continuous change of viscosity and electric conductivity during emulsification. The viscosity was measured with a torque meter equipped to the upper part of a stirring shaft. There was found a characteristic change at the stage of phase inversion. Plotting the highest viscosity in a phase inversion vs. HLB of combined surfactants showed two peaks with a depressed junction. Temperature range for phase inversion showed a similar pattern in reference to HLB. The middle HLB of the junction was assumed to be a required HLB. The required HLB was also confirmed with small and uniform particle size and good stability on aging at 30°. And surfactants suitable for oils may be selected on the basis of relations between the highest viscosity during phase inversion and HLB of combined surfactants. The present paper deals also with the phase inversion temperature in reference to HLB of combined surfactants.

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Benzo-c-thieno steroid, 1-methyl-3-acetoxy-5'-phenylthieno [4', 3', 2'-4, 5, 6] estra-1 (10), 2, 5, 9 (11)-tetraen-17-one was synthesized from 5'-phenylthieno [4', 3', 2'-4, 5, 6] androsta-5, 9 (11)-diene-3, 17-dione by means of dehydrogenation with DDQ followed by acid-catalyzed rearrangement.

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An aqueous solution of D-glucuronolactone (I) produces a yellow color by alkali. This yellow substance (II) was isolated from the precipitates obtained by treating I in dimethylformamide with potassium hydroxide in methanol at 70°. It had a strong reducing character, indicating the presence of oxo-ene-diol grouping in the molecule, and gave fumaric acid (VI) and 4-oxo-glutaconic acid (IV) on periodic acid oxidation. The structure of 3-keto-4, 5-dideoxy-trans-4, 5-dehydro-glucuronic acid was proposed to this new reductone.

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3-Keto-4, 5-dideoxy-trans-4, 5-dehydro-glucuronic acid is to exhibit various tautomeric forms in the solution. The possible tautomerism in acidic and alkaline medium was discussed on the basis of polarographic and absorption spectrographic data. Oxidation of the reductone by oxygen in alkaline solution gave disodium 2, 3-diketo-4, 5-dehydro-adipate, while oxidation of the reductone with iodine in acidic solution gave 4, 5, 6-trioxo-2, 3-dehydro-caproic acid which was isolated as bisphenylhydrazone.

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Several optical properties of α-methyl-α-amino acids (I), whose absolute configurations have already been established in our laboratory, were investigated, and compared with those of protein derived L-amino acids (II). On N-dithiocarbethoxy α-methyl-α-amino acids (III) with the same absolute configuration, the opposite ORDand CD curves were observed in the same solvent. Moreover, changes of direction of ORD and CD curves were not found by changing the solvent. These results were clearly different from those obtained on N-dithiocarbethoxy L-amino acids (IV). Examinations of Clough-Lutz-Jirgensons rule on I do not exhibit good relationships between absolute configurations and their positive values of [M]^HCl_D-[M]^H₂O_D. This reuslt was also different from that reported on II. However, hydantoin derivatives of I with (S)-configuration, showed large negative rotations with one exception, the same as those of II. From these studies, it has become apparent that the hydantoin rule is most useful for the assignment of absolute configuration of I.

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Some derivatives of 11-amino-2, 3-benzobicyclo [3. 3. 1] nonane and 3-phenyl-9-amino-bicyclo [3. 3. 1] nonane were synthesized from β-tetralon and 4-phenylcyclohexanone, respectively, through an enamine cyclization. Configuration and conformation of these bicyclic compounds were elucidated by nuclear magnetic resonance spectral analysis. A peculiar property, resembling to Sommelet reaction, of the amino group attached to bridged methylene in bicyclic system is presented. The mass spectra of the amino derivatives of bicyclo [3. 3. 1] nonane system are discussed.

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Irradiation of the title compound (I) at room temperature using a high pressure mercury lamp (450W) was found to yield 6β-methoxy-17β-acetoxyestra-5 (10)-ene (II : R=Ac) in 35% yield as an oily product. Along with a synthesis of this photoproduct (II : R=Ac) is also described that of its epimeric 6α-methoxy compound (IX : R₁=CH₃, R₂=Ac).

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Stepwise degradation of the polydigitoxosides of cardenolides was achieved by met-aperiodate oxidation, reduction and subsequent hydrolysis under the specified conditions in good yield.

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Futoquinol, isolated from Piper futokadzura SIEB. et ZUCC., has been characterized as a novel quinol-ether compound. The structure has been determined by means of 100 Mc NMR and chemical data of futoquinol and its derivatives obtained by dienone-phenol rearrangement.

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A crystalline constituent, futoenone ; C₂₀H₂₀O₅, mp 197°, was isolated from Piper futokazura and proved to have the structure (I). The result of regenerating futoenone from the diacetate (Va) via the tosyl-phenol (X), providing an interesting example of Ar₁-6 participation, strongly supported the spiro-dienone structure of futoenone. The stereochemistry was also proposed by the data of NMR. The total synthesis of futoenone was accomplished.

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1. For the purpose of clarifying the mechanism of mercapturic acid formation, properties of enzymes which catalyzed the conjugation of GSH with benzyl chloride (BzCl), bromobenzene (BrPh) and 3, 4-dichloronitrobenzene (DCNB) were examined in the liver of rats. 2. In addition to the supernatant fraction, a microsomal fraction was necessary for the enzymic conjugation of GSH with BrPh. 3. GSH-conjugating activity with BzCl was depleted in the liver of rats treated with BzCl. Either GSH-conjugating activity toward DCNB or BrPh did not show a significant change after the administration of each compound. 4. GSH-conjugating activity toward BrPh markedly increased in the liver of rats treated with phenobarbital, and its ratio of the stimulation was paralleled with that of aniline-hydroxylating activity. 5. It was assumed that increase of the activity of GSH-conjugation with BrPh by the treatment with phenobarbital was due to the induction of a microsomal oxygenase system.

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Infrared spectra of spermine phosphate hexahydrates C₁₀H₂₆N₄·2H₃PO₄·6H₂O and its N and O deuterated product have been measured. From the comparison of the spectra with those of the related simple molecules it is concluded that the salt is in the ionized form written [NH₃+(CH₂)₃NH₂+(CH₂)₂]₂·2[HPO₄]^2-·6H₂O.

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Ethyl 2-ω-cyanoethylamino-3-cyano-4-oxoquinolizine-1-carboxylate (VII) obtained from ethyl 2-methylthio-3-cyano-4-oxoquinolizine-1-carboxylate (V) as starting material for a new method of synthesis of dl-allomatridine (II).

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3-Dialkylaminosydnonimine salts (IV) were synthesized starting from 1, 1-dialkyl-hydrazines (I) via II and III. IV exhibits a remarkable stability towards acids and could be obtained as crystals. Chemical and physicochemical properties of IV were similar to those of known sydnonimine salts. It should be mentioned that intermediary nitroso compounds (III) were rather unstable and spontaneously gave rise to unsaturated nitriles (III').

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2-Methyl-3-o-tolyl-4 (3H)-quinazolinone (MTQ) was orally administered to human, and its urinary metabolites were examined. Two kinds of metabolite were isolated from the urine, and one of them was assumed to be 2-nitrobenzo-o-toluidide. On the other hand, the same compound as this metabolite was obtained by chemical oxidation of MTQ with hydrogen peroxide in glacial acetic acid. And the chemical structure of this oxidation product of MTQ was established as 2-nitrobenzo-o-toluidide. Therefore, one of the metabolites of MTQ, which were isolated from human urine by the authors, was confirmed to be 2-nitrobenzo-o-toluidide.

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Two metabolites were isolated as metabolic products of 2-methyl-3-o-tolyl-4 (3H)-quinazolinone (MTQ) in the 9000×g supernatant fraction of rabbits liver. These products were identified as 2-methyl-3-o-hydroxymethylphenyl-4 (3H)-quinazolinone (MHQ) and 2-methyl-3-o-tolyl-4 (3H)-quinazolinone N-oxide (MTQNO) by compairing with authentic samples. Ultraviolet absorption spectra, fluorescence spectra, paper chromatography and thin-layer chromatography with seven kinds of solvent system and paper electro-phoresis were employed for the identification.

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The metabolism of 2-methyl-3-o-tolyl-4 (3H)-quinazolinone-N-oxide in rabbits was investigated in vivo and in vitro. In vivo metabolism, 2-methyl-3-o-tolyl-4 (3H)-quinazolinone, 2-methyl-3-o-hydroxy-methylphenyl-4 (3H)-quinazolinone and 2-nitrobenzo-o-toluidide were found in the urine receiving 20 mg/kg of 2-methyl-3-o-tolyl-4 (3H)-quinazolinone-N-oxide, which have been considered to be a possible intermediate of 2-nitrobenzo-o-toluidide. In vitro metabolism, 2-methyl-3-o-tolyl-4 (3H)-quinazolinone-N-oxide was reduced preferentially to 2-methyl-3-o-tolyl-4 (3H)-quinazolinone (about 50-60%), while 2-nitrobenzo-o-toluidide was not detected. When the incubation of 2-methyl-3-o-tolyl-4 (3H)-quinazolinone-N-oxide with the liver preparation was carried out in oxygen, the formation of 2-nitrobenzo-o-toluidide was confirmed by thin-layer chromatography.

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2-Benzyl-4-chloro-5-mercapto-3 (2H)-pyridazinone (1) was heated in ethanol under reflux for 10 hours to form concurrently 2, 7-dibenzyldipyridazo [4, 5-b : 4', 5'-e]-1, 4-dithiin-1, 6 (2H, 7H)-dione (Ia) (57% in yield) and 2, 8-dibenzyldipyridazo [4, 5-b : 4', 5'-e]-1, 4-dithiin-1, 9 (2H, 8H)-dione (IIa) (14% in yield). Assignment of the two products to the corresponding structures is established by their physico-chemical constants and chemical behaviors. The concurrent formation of the dipyridazo [4, 5-b : 4', 5'-e]-1, 4-dithiin-1, 6 (2H, 7H)-dione and the -1, 9 (2H, 8H)-dione were observed in, not only heating 4-chloro-5-mercapto-3 (2H)-pyridazinones (1-3) in polar solvent, but warming 4-mercapto-5-chloro-3 (2H)-pyridazinones (4-6) in the presence of potassium carbonate in DMF. For the interpretation of the reaction, keto-thioketo carbenes as active intermediate species and a reversible interconversion among them are suggested on the basis of the fact that there was nonexistence of an equilibrium between the two compounds, such as Ia and IIa, under the reaction condition and a trapping keto-thioketo carbene species as 2-phenylimino-5-benzylpyridazo [4, 5-d]-1, 3-dithiol-4 (5H)-one (IVa) (14% in yield) along with the major products, (Ia) and (IIa), was furnished by warming 1 with phenylisothiocyanate in the presence of triethylamine in dry benzene. On the contrary, participation of a reversible interconversion between Ia and IIa, to a considerable extent, with the concurrent formation of them in the case of benzylation of either Ib or IIb, by warming with benzylchloride in the presence of potassium carbonate in DMF at 80°, might not be neglected, because an attempted approach to an equilibrium between Ia and IIa in a similar reaction condition except the use of benzylchloride realized, whereas non-existence of an equilibrium between Ib and IIb in the similar reaction condition was observed.

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The Pariser-Parr-Pople SCF calculation has been carried out with the aid of the variable β-core method for the investigation of the π-electronic structure of riboflavin. Comparison between the experimental and theoretical results on the transition energy and intensity, and the direction of transition moment of π-π bands in the electronic spectra is presented, together with the π-electron densities and free valences of the lowest singlet and triplet excited states which have been calculated with the aid of configuration interaction method. It has been found that the π-electron distribution of the photo-excited state is in parallel with the experimental facts suggesting a photo-induced change of basicity and a direct hydrogen-transfer in anaerobic photobleaching reaction.

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For the purpose of testing the biological activity, spiro [1, 2, 3, 4-tetrahydro-7-methoxy-2-methyl-5H-2-benzazepine-5, 1'-4'-hydroxycycloheptane] (IV) and its isomer (V) were synthesized by a sequence of reactions including ring enlargement of the acetoxy-1-tetralone (XXV) to a seven-membered nitrogenous ring compound (XXVI and XXVII) by the use of Schmidt reaction.

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An attempt was made to synthesize 9-β-D-xylofuranosylguanine (VI) by condensation of N², N^9(or7)-diacetylguanine (I) and 1, 2, 3, 5-tetra-O-acetyl-D-xylofuranose (II) by a fusion method. However the main product obtained was 7-xylofuranosylguanine (III). Compound VI was successfully synthesized by deamination of 2-chloroadenine xyloside derivative (IV) with nitrous acid followed by amination with ammonia. VI was enzymati cally phosphorylated to give 9-β-D-xylofuranosylguanine 5'-phosphate. This Compound was found to have a flavoring activity. Catalytic hydrogenation of 2-chlorohypoxanthine derivative (V) with palladium-charcoal afforded hypoxanthine xyloside (IX), which, after acetylation, was chlorinated with phosphorus oxychloride to give the chloro compound (XII). This was converted by reaction with thiourea and subsequent ammoniacal treatment to 9-β-D-xylofuranosyl-6-mercaptopurine (XIII).

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In order to find out the method for a biological detection of luteoskyrin, a hepatotoxic anthraquinone of Penicillium islandicum Sopp, we investigated the inhibitory effect of mycotoxins on the growth rate of Escherichia coli F-11 and Q-13. The results were summerized as follows ; 1) 0.4 μg/ml of (-)-luteoskyrin or 1.5 μg/ml of (+)-rugulosin, hepatotoxic anthra-quinoes of Penicillium islandicum Sopp or Penicillium rugulosum, caused the 50% inhibition of the growth of E. coli F-11, an actinomycin D sensitive mutant derived from E. coli Q-13, without affecting the parent type. 2) 2-5 μg/ml of patulin, (-)-rugulosin and penicillic acid inhibited the both bacteria. 3) Sporidesmin, flavoskyrin, catenarin and emodin inhibited slightly E. coli F-11. 4) No inhibition was observed with chlorine-containing peptide, islandicin, ascradiol, nivalenol, fusarenon-X, rubratoxin B, aflatoxin B or citrinin. 5) E. coli F-11 is considered to be a simple tool for the microbial assay of the hepatotoxic luteoskyrin or rugulosin contaminated in fungi-polluted cereal grains or foodstuffs.

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Photolysis of an aqueous ethanolic solution of p-toluenesulfonamide (IId-f, IIIe-h, IVc-d and Vd-f) and Na₂CO₃ in the presence of NaBH₄ was found to give the corres-ponding free amine (IIa-c, IIIa-d, IVa-b and Va-c) in moderate yield. The mechanistic pathway of this reaction was deduced.

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The critical distance, R₀, which is the rate parameter for the transfer of excitation energy by resonance between aromatic amino acids and 14 kinds of non-steroidal anti-inflammatory drugs or some of other aromatic compounds was calculated. The rank correlation between the R₀ values and anti-inflammatory activity were found to be significant, and the activity of various nonsteroidal anti-inflammatory drugs were illustrated uniformly at a molecular level. Finally, a possibility of formation of electronic excited state of aromatic amino acid residues in living cell was discussed.

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Hansch-Fujita's equation has been applied to an analysis of the natriuretic activity of sulfonamide carbonic anhydrase inhibitors using π and π_e as hydrophobic parameters, and σ, △pK_a, △ppm and △f_r as electronic parameters. Sixteen benzenesulfonamide derivatives were satisfactorily applied to the structure-activity analysis of heterocyclic sulfonamides. It was concluded that a strong natriuretic activity was observed for sulfonamides which had an optimal hydrophobicity and low electronegativity at the sulfamoyl group or a strong inhibitory activity against carbonic anhydrase.

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