Arylnickel and arylpalladium complexes which were easily prepared from aryl halide having internal double bond and the low valent metal complexes gave indole, oxindole, quinoline, isoquinoline and benzazepine derivatives. These reactions were highly regiospecific because the reaction occurred at the position of the halogen atom of the aromatic ring and the exo-position of the double bond. Since the insertion of carbon monoxide to this aryl or vinylmetal complex gave acylmetal complex, aryl and vinyl halide having functional group such as amine, alcohol and amide were treated with a catalytic amount of Pd^II and PPh₃ under carbon monoxide to give benzolactam, benzolactone, cyclic imide and α-methylene lactam and lactone. By using this method, α-methylene-β-lactams and α-alkylidene-β-lactams were synthesized from 2-bromo-allylamine derivatives. Moreover, natural compounds, sendaverine, anthramycin skeletone and 3-aminonocardicinic acid were synthesized by this method.

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An interaction between Ni²⁺ and purine derivatives, such as adenine, 6-chloropurine, 6-hydroxypurine, 6-methylpurine, 6-mercaptopurine and purine, at a mercury electrode-electrolyte interface was investigated. In the presence of purine derivatives, a catalytic prewave of Ni²⁺ prior to their reduction waves was observed on a direct current (DC) polarogram. The prewave was affected by the concentrations of Ni²⁺ and purine derivatives. Addition of gelatin caused the disappearance of the prewave, suggesting that the electrode process of the prewave involves the adsorption of purine derivatives and/or their complexes with Ni²⁺ on the electrode surface. Effects of concentration and nature of cation of supporting electrolyte (nitrates were used) were also examined : The prewave height (i_pre) was markedly lowered with increasing concentration and i_pre was given in the order of Li⁺>Na⁺>Cs⁺. On the basis of the experimental results, a possible reaction mechanism was proposed taking the following facts into consideration : Ni (H₂O)₆²⁺ is transported to the electrode surface through diffusion, then the complex formation takes place immediately between Ni²⁺ and preadsorbed purine derivatives, and the resulting complexes are more easily reduced than Ni (H₂O)₆²⁺.

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In order to develop the most excellent stabilizer for ascorbic acid, various phosphoric acids and phosphates were examined and the effects of concentrations, temperatures and metal ions on the stability of ascorbic acid were also investigated. 1) Among various phosphoric acids and phosphates, sodium trimetaphosphate (P_3m) was found to be most effective for the stability of ascorbic acid. A considerable effect was also observed in sodium dihydrogen pyrophosphate (P₂) and metaphosphoric acid (P_m). 2) The rate of the oxidation of ascorbic acid increased with a decrease in concentration of phosphoric acids or phosphates used. 3) Ascorbic acid tended to be oxidized with increasing temperature and at 70°no difference in the kinds of phosphates could be detected for the stability of ascorbic acid. At a temperature as low as 10°, ascorbic acid was highly stable irrespective of the kinds of phosphates. 4) In the presence of various metal ions, P_3m, P₂ and P_m were also effective for the stability of ascorbic acid.

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The ¹³C-NMR spectra of 6-and 6'-O-tritylcellobiose peracetates and methyl 6-and 6'-O-tritylcellobioside peracetates in chloroform-d were determined. ¹³C signals were assigned by chemical shift comparisons with α- and β-D-glucopyranose pentaacetates, methyl β-D-glucopyranoside tetraacetate, methyl 6-O-trityl-β-D-glucopyranoside triacetate, methyl 4-O-methyl-β-D-glucopyranoside triacetate, methyl 4-O-methyl-6-O-trityl-β-D-glucopyranoside diacetate, and α-and β-cellobiose octaacetates. It was found that ¹³C-NMR spectroscopy is a useful tool for determining which position of 6-or 6'-primary alcohol group is substituted with a trityl group. The effects of 6-and 6'-O-trityl substitutions upon the conformation around the interglycosidic linkage of the cellobiose are discussed by using the trityl substitution shifts in ¹³C-NMR and by comparing the conformation of 6-O-trityl-α-cellobiose heptaacetate in the crystalline state obtained by an X-ray analysis.

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The rates of nitrosation of cyclohexanecarboxylic acid (CCA) with nitrosyl hydrogensulfate (NHS) in 7.29-14.28% oleum forming ε-caprolactam have been followed by the volumetric determination of evolved carbon dioxide. The reaction dose never occur without sulfur trioxide. The rate of the reaction is expressed by Rate={k_2cs-k_3cnsC_NHS}C_CCAC_SO3-{k_2cc-k_3ccnC_NHS}C²_CCA A probable mechanism which involves pentamethyleneketene (PMK) formed by the elimination of sulfuric acid and proton from the protonated hexahydrobenzoyl hydrogensulfate (2) and proton, and the cyclohexanecarboxylic anhydride (CCAN) formed by the elimination of proton, sulfur trioxide and water from on adduct of 2 and CCA, was discussed.

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Stereoselective reduction of 2-amino-1-propanones having heterocycles as substituent was examined under several conditions. Sodium borohydride reduction of their hydrochlorides afforded stereoselectively the corresponding erythro-alcohols, and the same results are obtained by the reduction with diborane. This paper also describes the effect of reaction temperature, solvent and molar ratio of reducing agent on the stereoselectivity on reduction.

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Additional thirteen minor alkaloids (including an N-acetyl compound) were isolated from Stephania sasakii HAYATA. Among them, N-acetylstepharine, 7-oxocrebanine and dehydrophanostenine were new naturally occurring products, and the formulas 3, 14 and 12, determined from various spectral data and their chemical reactions, respectively. The others were five known compounds, such as N-methyl-6, 7-dimethoxy-1-isoquinolone (1), dehydroroemerine (9), cepharadione-A (15), lysicamine (13), cepharamine (16) and five unidentified alkaloids (Tentatively named E, F, G, H and I).

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Tow stable secondary products derived from the autoxidation of methyl linolenate were separated by column and high performance liquid chromatographies. Each secondary product showed ultraviolet absorption spectrum at 230 nm and 250-260 nm, and reacted with 2, 4-dinitrophenylhydrazine. However, secondary products treated with sodium borohydride resulted in the disappearance of ultraviolet absorption spectrum at 250-260 nm and reactivity with 2, 4-dinitrophenylhydrazine. Each secondary product formed six fluorescent substances with stearylamine, and all these fluorescent substances showed excitation maxima at 350-360 nm and emission maxima at 420-430 nm. However, characterization of these fluorescent substances differed from those which formed from stearylamine or other amino compounds with malondialdehyde. These results suggest that secondary products had conjugated diene structure with aldehyde group and that several lipofuscin-like fluorescent substances would be formed by the reaction of various amino compounds with secondary product with aldehyde group.

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The method for the analysis of binding parameter fitting for drug-protein interaction by use of a pocket programmable calculator from curvilinear Scatchard plot in the case of two independent sets of the binding sites is described. The comparison of this analysis with a non-linear regression analysis by least square method by using a digital computer showed that the calculator solution is as rigorous as and/or more flexible than the computer solution especially for the fitness of the scattered binding data and also much more accessible. The method is applied to estimate the binding parameters for the practical binding data of caprylic acid and tolbutamide with serum albumin obtained from the radiostereo assay.

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The pharmacological actions of sodium alginate on the mucosa of the upper gastrointestinal tract were studied by in vivo and in vitro experiments. To induce the experimental gastric erosion, rats were administered orally with 500 mg/kg of aspirin, and subsequently treated with oral administration of 5% (w/v) solution of sodium alginate. Histopathological observation of the stomach of these rats showed that sodium alginate formed a thick layer and covered the foci of aspirin-induced erosion. It was suggested that the layer of sodium alginate restrained the destruction of tissues and hemorrhage at the foci of erosion. The digestion of the mucosa of the excised rat stomach or rabbit esophagus in artificial gastric juice was highly inhibited when the mucosa was previously treated with 5% solution of sodium alginate. This was evidenced by the fact that significantly fewer amount of tyrosine was separated into the incubation medium from the alginate-treated stomach or esophagus as compared with untreated controls. Sodium alginate showed only weak antacid or no anti-pepsin actions. Accordingly, it was suggested that the layer of sodium alginate covering the lesion may inhibit the lytic action of pepsin and hydrochloric acid, and may protect the mucosal surface of the stomach and esophagus mainly by its mechanical action.

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The hemostatic activity of sodium alginate was studied by in vitro and in situ experiments and by a clinical application. 1. 5% solution of sodium alginate did not gelatinize when mixed with rat plasma in vitro, but easily gelatinized in the coexistence of rat plasma and rat gastric juice or artificial gastric juice. 2. 5% solution of sodium alginate did not gelatinize in the presence of calcium ion equivalent to the concentration of Ca²⁺ in plasma (10 mg/dl), and more than 70 mg/dl of calcium was required to cause an intense gel formation. 3. The sedimentation and diffusion velocities of the peripheral blood of rabbits in the sodium alginate solution were delayed as the concentration of sodium alginate increased. 4. Bleeding from the injury of rat gastric mucosa caused by a biopsy was significantly interrupted earlier than controls when 5% solution of sodium alginate was applied to the injury. 5. In a clinical application, 5% solution of sodium alginate also suppressed the bleeding from the injury of human gastric mucosa caused by a biopsy.

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The solubility of fibrinogen, fibrin clotting time from fibrinogen and polymerisation of fibrin monomer in the presence of sodium alginate were examined. Sodium alginate precipitated fibrinogen, shortened fibrin clotting time and increased fibrin polymerisation rates. These effects increased with an increase in the molecular weight and concentration of sodium alginate.

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Aminopyrine and its molecular compounds with barbiturates were commonly used in humans as analgesics and antipyretics. These compounds showed potent teratogenicity. Pregnant ICR/Jcl mice received 3 s.c. injections of pyrabital (2 molecules of aminopyrine and 1 molecule of barbital) daily on days 9, 10 and 11 of gestation. Significant yields of late deaths and malformations were induced at doses more than 0.2 mg/g body weight, and clear dose-relationship was observed. Most malformations were ruptured omphaloceles (eventration of the abdominal viscera), which are extremely rare in mice. Equivalent doses of aminopyrine contained in pyrabital also induced late deaths and malformations. However, in each case, the incidence of malformations was significantly lower than that by pyrabital. When aminopyrine (0.21 mg/g) and barbital (0.09 mg/g) were given separately to pregnant mice on days 9, 10 and 11 of gestation, teratogenicity was approximately equal to that by the equivalent dose of molecular compound (0.3 mg/g). Consequently, potent teratogenicity of pyrabital is independant of the molecular compound, but depends only on the presence of baibital with aminopyrine.

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Aminopyrine and its molecular compound with barbital (Pyrabital) showed potent teratogenicity, whereas an equivalent dose of its molecular compound with cyclobarbital (Cyclopyrabital) showed very weak teratogenicity. Even if aminopyrine was given subcutaneously to the right flank of pregnant mice and barbital given to the left flank at the same time on days 9, 10 and 11 of gestation, teratogenicity was approximately equal to that by the equivalent dose of molecular compound, but significantly higher than that of aminopyrine alone. When barbital was given as a suspension in 1% gelatin solution, it strongly enhanced aminopyrine-initiated teratogenesis, while cyclobarbital did not. Barbital might induce an enzyme responsible for transforming aminopyrine to teratogenic forms, since pre-treatment of aminopyrine with barbital on days 5, 6, and 7 significantly enhanced teratogenicity initiated by aminopyrine. Pre-treatment with phenobarbital also enhanced aminopyrine-initiated teratogenesis, while it did not enhance X-ray-initiated one.

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From Ipomoea biloba FORSK, isoquercitrin monoacetate (I), isoquercitrin (II), hyperin (III) and quercetin 3-sodium salt (IV) were isolated.

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Two kinds of reactions were carried out on the components of the seeds of Hernandia ovigera L. The reaction of lead tetraacetate on desoxypodophyllotoxin (I) and its analogous compounds caused the cleavage of methylenedioxyl group, affording the corresponding diphenols. In the case of 3, 4-methylenedioxypropylbenzene (XII), an intermediate acetoxyl compound (XIII) was isolated. The reactions of 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) on I and its analogous compounds afforded smoothly aromatized compounds. By the same reaction on bursehernin (III), cyclization and aromatization occurred simultaneously affording chinensin (XVIII) which was confirmed by direct comparison with authentic speciemen. The results of the cleavage reaction on I and XII by use of borontrichloride were also described.

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As a part of the investigations on the stability of furosemide (4-chloro-N-furfuryl-5-sulfamoylanthranilic acid) (1), acid hydrolysis of 1 was kinetically examined in alcoholwater mixtures. 1 was hydrolyzed with hydrochloric acid in the mixtures to yield 4-chloro-5-sulfamoylanthranilic acid (2) as a main decomposition product, and this degradation of 1 proceeded in pseudo first-order reaction. The hydrolysis rate constant (k_obs), when determined at various values of ionic strength (μ), dielectric constant (D) and temperature (T), became greater as these parameters were raised. The activation energies at μ=0.5 and D=55, calculated by Arrhenius equation, were 34.0 kcal/mol in a methanol-water mixture and 39.7 kcal/mol in an ethanol-water mixture. The half-lives (t_1/2) at 20°were 19 days and 79 days in methanol-and ethanol-water mixtures, respectively.

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