In the presence of ammonia or amine some azomethines were catalytically hydrogenated under high hydrogen pressure to give two kinds of amines according to the equation : [chemical formula] In the pathway of this hydrogenation reaction, the first stage preceding hydrogenation was proposed to be the replacement reaction of amine residue of azomethine by that of ammonia of amine. This was demonstrated using N-benzylidene-4-sulfonamidobenzylamine as azomethine.

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The condensation of 3'-iodo-5-benzoyloxy-4', 7-dimethoxyflavone and 5-benzoyloxy-8-iodo-4', 7-dibenzyloxyflavone was carried out at 225∼230°for 40 minutes, with activated copper powder. The chloroform extract of the reaction mixture was heated with 10% H₂SO₄ in AcOH at 110° for 10 minutes to hydrolyze benzoyl and benzyl groups. The hydrolysate was dissolved in a mixture of dioxane and ether, and shaken with 10% K₂CO₃ solution to obtain yellow, sandy crystalline precipitate of potassium salt of ginkgetin. This salt was purified by recrystallization from 10% K₂CO₃ solution, decomposed with dilute H₂SO₄, and the free ginkgetin obtained was recrystallized from methyl ethyl ketone to pale yellow, small plates, m.p. 336°. Its acetate formed colorless needles, m.p. 259°. Ginkgetin and its acetate synthesized above were respectively identified with the corresponding materials of natural origin.

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trans-9-Methyl-(XIa) and -9-aminomethyl-2-decalones (VIII) were prepared from the parent trans-2-oxo-9-decalincarbonitrile (I) by a series of reductions and were characterized.

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Our previous method of prepraring azapyrimidine nucleosides is suitable for the preparation of 2-β-D-ribofuranosyl-5-amino-as-triazine-3 (2H)-one (6-azacytidine) (V). For the preparation of 2-β-D-ribofuranosyl-as-triazine-3, 5 (2H, 4H)-dione (6-azauridine) (VI), however, an alternative route by way of 2-(2', 3', 5'-tri-O-benzoyl-β-D-ribofuranosyl)-5-methylmercapto-as-triazine-3 (2H)-one (III) was found to be more convenient than the previous one. The procedure was also improved.

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Solid nickel peroxide has been shown to be capable of oxidizing aromatic primary amines to the corresponding azo-compounds in benzene solution. Benzylamine and its derivatives bearing a substituent in the benzene ring could be easily oxidized by the same oxidant to give the corresponding nitriles in good yields regardless of the position and the variety of a substituent. Alkyl amines also underwent similar oxidation. In addition, the mechanisms of these oxidations were discussed.

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A sensitive spot test for active methylene compounds was established by adding sodium dihydrogen phosphate in the alkaline reaction mixture of either trinitrobenzene or picric acid. A blank color faded or diminished in this method, and the developed coloration increased wtih a few exceptions. The color and a limit of detection of many active methylene compounds were tabulated.

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As exploratory experiments for the synthesis of 3-hydroxymethyl-4, 5, 7-trimethoxy-2-naphthoic acid γ-lactone in the course of synthethic studies on α-sorigenin, the synthesis of 3-hydroxymethyl-4-methoxy-2-naphthoic acid γ-lactone (VI) was accomplished by the two routes shown in Chart 1 and 2.

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4-Oxo-5, 7-dimethoxy-1, 2, 3, 4-tetrahydro-2-naphthoic acid (VII) is expected to serve as a key intermediate in the synthesis of the proposed structure for α-sorigenin dimethyl ether (3-hydroxymethyl-1, 6, 8-trimethoxy-2-naphthoic acid γ-lactone (I)). The reported method for VII was improved and the synthesis of 3-hydroxymethyl-4, 5, 7-trimethoxy-2-naphthoic acid γ-lactone (II) started with VII was carried out. The reaction scheme is shown in chart.

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The lithium aluminum hydride reduction of the half ester VIII, obtained by alcoholysis of 1, 6, 8-trimethoxy-2, 3-naphthalenedicarboxylic anhydride (VII), afforded two kinds of lactones of m. p. 185°and m. p. 202°, among which the former lactone of m. p. 185°was shown to be identical with natural α-sorigenin dimethyl ether, and the latter lactone of m. p. 202°with 3-hydroxymethyl-4, 5, 7-trimethoxy-2-naphthoic acid γ-lactone (X) prepared in the previous paper. Thus, the structure of α-sorigenin dimethyl ether was proved to be 3-hydroxymethyl-1, 6, 8-trimethoxy-2-naphthoic acid γ-lactone by synthetic means.

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The synthesis of α-sorigenin dimethyl ether, 3-hydroxymethyl-1, 6, 8-trimethoxy-2-naphthoic acid γ-lactone (I), by an unequivocal route as shown in chart is described. The reactions employed for preparing the 1-oxo-3-hydroxymethyl-1, 2, 3, 4-tetrahydro-2-naphthonitrile (VII) from the ethyl 1-oxo-1, 2, 3, 4-tetrahydro-2-naphthoate II via the intermediates, III, IV, and VI, would provide a new method for protecting the keto-group towards lithium aluminum hydride reduction.

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The physiological disposition and the metabolic fate of hypnotic, 2-methyl-3-o-tolyl-4 (3H)-quinazolinone (MTQ), were studied in man, rat and rabbit. MTQ is rapidly absorbed from the gastrointestinal tract in man and rat. The concentraton of the drug in depot fat is remarkably high compared with that in other tissues in rat. The drug is almost completely metabolized in the body and the rate of biotransformation of the drug is relatively slow. Glucuronides excretion after oral administration of 200 mg./kg. of MTQ was about 20% in a rabbit.

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D-Threonine and D-lysine were clearly proved to inhibit the growth of Ehrlich solid tumor in the inguinal region of mouse hindleg but its mechanism has not been clarified as yet. These amino acids showed no effect in the prolongation of life of mice bearing Ehrlich ascites tumor.

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It is shown from the nuclear magnetic resonance data of 23 kinds of androst-4-ene and pregn-4-ene derivatives that nuclear magnetic resonance can be applied to determination of the position and the configuration of unknown hydroxyl groups in steroidal molecules.

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Cyclohexanone derivatives, having one or no carboxylic group at α-position of the keto group, were allowed to react by Mannich reaction to give azabicyclononanone compounds. Of these compounds 5-(m-or p-methoxyphenyl)-1, 3-dimethyl-3-azabicyclo-[3. 3. 1] nonan-9-one is a valuable starting material for the synthesis of a diterpenoid alkaloid nucleus.

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N-Oxidation of 4-chloro-3, 6-dimethylpyridazine (II) with monoperphthalic acid gave 4-chloro-3, 6-dimethylpyridazine 1-oxide (III) and 5-chloro-3, 6-dimethylpyridazine 1-oxide (IV). The order of reactivity of these chloro-compounds in nucleophilic substitution are IV>II>III.

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Nitration of pyridazine 1-oxide (I) with acyl nitrate afforded two kinds of β-nitropyridazine 1-oxide, i. e., 3-nitropyridazine 1-oxide (III) as a main product and 5-nitropyridazine 1-oxide (IV) as a poorly yielded by-product. Structural correlations of those nitro compounds to known pyridazine derivatives were achieved by catalytic hydrogenations or nucleophilic displacement reactions of the active nitro group. Furthermore, some nucleophilic substitution reactions of III and 3-chloropyridazine 1-oxide were described.

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Treatment of 3, 6-dichloropyridazine (III) with sodium azide resulted in the formation of a mixed azido-tetrazolo compound (IV). 3-Azidopyridazine 1-oxide (X) and 6-azidopyridazine 1-oxide (XIX) were synthesized from the corresponding hydrazino compounds (XII, XVII) with nitrous acid, and also from chloro compound IX with sodium azide. Then several reactions, such as ionic reaction, catalytic hydrogenetion, thermal decomposition, reactions with phosphorus trichloride and with phosphorus oxychloride, and reaction with DPPH of these azides were examined.

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Es wird die Reduktionsreaktion des C₆-Carbonyls von Morphinalkaloid mittels T. sanguinea beschrieben. Die Umsetzung des Dihydrocodeinons ergibt die entsprechenden epimeren 6-Ole. Bei der Umsetzung des Dihydrothebainon-methylathers bzw. des 4-Desoxydihydrothebainons verlauft aber diese Reduktion nicht glatt. Sinomenin und seine Derivate lassen sich auch durch diese Mikroorganismen nicht angreifen.

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The biosyntheses of monascorubrin and monascoflavin by a strain of Monascus genus have been studied and the two pigments have shown to be derived from the linear condensation of acetic acid units. The results confirm the proposed structure of both pigments.

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The biogenesis of thymol in Orthodon japonicum BENTH. et OLIV. was studied by radioisotope tracer technique. It has been established that thymol is biosynthesized from acetate via mevalonate by the general pathway of isoprenoid biosynthesis.

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From the mycelium of Penicillium hirayamae UDAGAWA two hitherto undescribed metabolites have been isolated. The major product is a levorotatory isomer of the known sclerotiorin. The minor component, rubrotiorin, C₂₁H_21∼23O₄Cl, m. p. 172°, is given as red needles and appears to be a new azaphilone compound.

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Penicillum brunneum UDAGAWA was fed with malonate [2-¹⁴C], and rugulosin-¹⁴C isolated from the mycelia was degraded to prove that the terminal C-CH₃ group was not labelled with ¹⁴C. Using acetate [1-¹⁴C] with or without competition of inactive malonic acid, a predominant incorporation of acetate unit into the terminal C-CH₃ unit was revealed. It has been established that the fungal anthraquinone series compounds are biosynthesized by the malonate-acetate condensation.

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An amorphous glucoside, named paeoniflorin, which was isolated from the roots of Paeonia albiflora PALLAS yielded crystalline tetraacetate, C₃₁H₃₆O₁₅, and pentaacetate, C₃₃H₃₈O₁₆. Alkaline hydrolysis showed that paeoniflorin possesses a benzoyl group. On treatment with lithium aluminium hydride, the acetates afforded product A, C₁₆H₂₄O₁₀. Methylation of paeoniflorin tetraacetate yielded a methyl ether, C₃₂H₃₈O₁₅ (product E acetate). By the action of lithium aluminium hydride, the product E acetate was converted into product F, C₁₇H₂₆O₁₀. On treatment with sulfuric acid, the product F was hydrolyzed to yield an amorphous aglycone (aglycone F) liberating D-glucose. Oxidation of the aglycone F with cromium trioxide afforded a yellow crystalline quinonic compound (aglycone H), C₁₀H₁₀O₄. The nuclear magnetic resonance spectral analysis of aglycone H leucodimethyl ether showed that it should be represented as 2-(4-methyl-2, 5-dimethoxyphenyl) or 2-(3-methyl-2, 5-dimethoxyphenyl) propionic acid. Paeoniflorin was shown to be D-glucoside of benzoylated C₁₀-compound (C₁₀H₁₄O₅).

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2-(2, 5-Dimethoxy-4-methylphenyl) propionic acid (XII) was synthesized and proved to be identical with aglycone H leucodimethyl ether which was derived from paeoniflorin, a glucoside of Chinese Paeony root.

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A new glucoside, C₂₃H₂₄O₁₀·H₂O, m. p. 209∼210°, [α]¹²_D -67.15° (c=1.43, acetic acid) was isolated from Wistaria floribunda DC. and some allied plants, and named wistin. The aglycone of wistin was proved to be identical with afromosin (=7-hydroxy-6, 4'-dimethoxyisoflavone (II)), which had been isolated by McMurry et al. from Afromosia elata HARMS. Wistin was formulated as in I.

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By means of paper chromatography, it was fonud that DHA was very reactive with ammonia, ammonium chloride, methylamine, ethanolamine or aniline in aqueous solutions even under a mild condition such as keeping in an incubator (37°), and pyridone derivatives were easily formed via Schiff's base type compounds (the first reaction product). It was also observed that DHA had lost its activity against some bacteria and fungi when it reacted with ammonia or primary amines.

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The reaction process of DHA, when it reacted with an excess of methyl-, ethyl-benzyl- or phenethylamine under a mild condition, was clarified as follows : The primary reaction product is Schiff's base, the secondly product 2, 6-bis (alkylamino)-2, 5-heptadien-4-one, and the final product lutidone derivative. In the case of the reaction of DHA with an excess of ammonia, two compounds, lutidone and lutidonecarboxylic acid, were obtained as final products. But lutidonecarboxylic acid seems not to be the intermediate to lutidone under these mild conditions.

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1. While the isotonic phosphate buffer (pH 6.0∼6.4) was recirculatingly perfused through the rat small intestine for 3 hours, volume of the solution was constant. 2. When the isotonic phosphate buffered solution (pH 6.0∼6.4) containing sulfonamide was recirculatingly perfused through the rat small intestine in vivo, the logarithm of residual ratio of the drug vs. time curve was a straight line. 3. From the slope of the straight line, apparent permeability coefficient, p_a, was obtained. The constants were : Sulfaguanidine (0.0×10^-3 cm./min.) ; Sulfathiazole (0.9×10^-3) ; Sulfanilamide (1.0×10^-3) ; Sulfamethoxypyridazine (1.7×10^-3) ; Sulfisomezole 3.2×10^-3). 4. It may be suggested that the permeability coefficient of sulfisomezole from intestinal lumen (isotonic phosphate buffered solution at pH 6.0∼6.4) into plasma is much larger than that from plasma into intestinal lumen. 5. The P_a-pH diagrams of four sulfonamides were obtained.

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Penicillium brunneum UDAGAWA was shown to produce rugulosin in good yield accompanying skyrin and emodin.

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