In order to examine the effect of bulky substituents on the reductive cleavage of aminoxazoles, benzyl 4-R1-5-R2-2-oxazolecarbamate (I) and 2-amino-4-R1-5-R2-oxazole (II) were synthesized by the route shown in Chart 1 and 2. The nuclear magnetic resonance (NMR) spectra of the benzene protons in oxazole derivatives were examined. In 4, 5-alkyl and 4, 5-phenyl compounds proton peaks appeared as a singlet for the phenyl group at the 5-position and as a multiplet for the phenyl group at the 4-position. The latter was considered to be due to the strong effect of the lone pair electrons on the ring nitrogen.
In order to examine the reductive cleavage of aminoxazoles, benzyl 4- and 5-oxazole-carbamates (I and II) were synthesized, and then submitted to catalytic reduction. When using palladium-carbon catalyst in ethanol, I was converted to a brown resin, but II afforded acylaminonitriles (IV) by the conversion of 5-aminoxazoles (III) formed. I and II were converted to acetamidoxazoles (V and VI) when using palladium-carbon catalyst in acetic anhydride. V and VI were easily converted to the corresponding ethylidenebisamides (VII) and ethylenebisamides (VIII) by ring fission when using platinum oxide in acetic acid. V was recovered but, with the exception of 2, 4-dimethylated VI (VIa), VI gave VIII when using palladium-carbon catalyst in ethanol.
Anaerobic decomposition of L-ascorbic acid in the presence of D-araboascorbic acid in aqueous solution was studied. Separation and determination of L-ascorbic acid and D-araboascorbic acid in their mixed aqueous solution were carried out by gas-liquid chromato-graphy. Anaerobic decomposition of L-ascorbic acid alone and D-araboascorbic acid alone was examined at various temperatures (40°, 50°, 65°) and pH values (pH 1.0-6.0). The pH-rate profile of the two compounds clearly showed a maximum at pH=pK1 and the optimum pH for the stability was found to be pH 6.0. The shape of the pH-rate profile of L-ascorbic acid varied with temperature, but that of D-araboascorbic acid varied little with temperature. The present experimental data on anaerobic decomposition of L-ascorbic acid at 40°, 50°, and 65° were in good agreement with the theoretical values calculated from the equation proposed by Higuchi. From kinetics, it seemed reasonable to assume, also in the case of D-araboascorbic acid, the formation of a complex between undissociated araboascorbic acid and monohydrogen araboascorbate. The decomposition of L-ascorbic acid in the presence of D-araboascorbic acid was faster than that of L-ascorbic acid alone. The stabilizing effect of D-araboascorbic acid for the decomposition of L-ascorbic acid was not observed in the anaerobic aqueous solution.
Application of ethyl chlorocarbonate to the dilithium derivative of furylethynylcarbinol (4) afforded o-ethoxycarbonyl (7), rather than γ-hydroxy-α, β-acetylenic ester (9b). The latter esters (9a and b) were obtained easily by the application of the Grignard derivatives (11a and b) of acetylenic esters (8a and b) to furfural, Treatment of γ-hydroxy-α, β-acetylenic esters (9a and b) so obtained with activated manganese dioxide gave α, β-acetylenic-γ-keto esters (10a and b).
Multiplicity and properties of proteinases from the latex of Ficus carica var. HORAISHI, which grows in Japan, were examined. Four proteinases were found in the latex by polyacrylamide gel electrophoresis. They were purified to homogeniety from the latex and Ficins A and B were crystallized. The molecular weight of each of these enzymes was 24000 to 26000. They showed similarity in optimum pH, pH stability, and hydrolysis ratio on casein substrate, but differed in affinity to carboxy methyl cellulose, mobility in polyacrylamide gel, optimum temperature, heat stability, and specific activity on various substrates. These results suggest that four or more proteinases exist independently in the latex of Ficus carica var. HORAISHI.
Twenty-five 5-nitro-2-furyl thioethers and two 5-nitro-2-furyl sulfones were prepared for the purpose of screening their antibacterial activities. Mass spectra of these compounds were measured and several characteristic fragmentations were observed. Ultraviolet spectra of 5-nitro-2-furyl thioethers were measured and relationship between the absorption maxima and antibacterial activity was examined. Some members of the series displayed high antibacterial activity in vitro against gram-positive and gram-negative organisms.
Reaction of deoxynupharidine (I) with acetylchloride, nitric acid, and p-nitro benzene-diazonium chloride gave 5'-acetyl-(II), 5'-nitro- and 5'-(4-nitrophenyl)-derivatives, respectively, but not 2'-substituted products. Heating of II in aqueous ammonia containing ammonium chloride afforded 1, 7-dimethyl-4-(3-hydroxy-2-methyl-5-pyridyl)-octahydro-quinolizine (IX).
5-Chloro-2-(N-methyl)phthalimidoacetamidobenzophenone was obtained in a good yield by the condensation of 5-chloro-N-methyl-N-phthalimido acetylanthranilic acid with benzene using the Friedel-Crafts reaction. A similar condensation of N-aminoacetyl-5-chloro-N-methylanthranilic acid with benzene gave Diazepam. Diazepam was also prepared by the condensation of 2, 4'-dichloro-N-methylacetanilide with benzonitrile, in the presence of titanium tetrachloride.
In order to examine the effect of bulky substituents on ring fission, benzyl 4-R1-5-R2-2-oxazolecarbamate (I) and 2-amino-4-R1-5-R2-oxazole (II) were submitted to catalytic reduction. I was converted to II when using palladium-carbon-B in ethanol. Excepting 5-alkyl-I and 4-tert-butyl-5-phenyl-I (In), I afforded 1-R1-2-R2-ethylurea (III) when using palladium-carbon-A catalyst in ethanol. When using platinum oxide in acetic acid, 5-methyl (Id) and aralkyl-I were converted to 1-benzyloxycarbonyl-3-(1-R1-2-R2-ethyl) urea (IV), 5-ethyl (Ie) and 5-isopropyl (If) afforded a mixture of III and IV, and 5-tert-butyl (Ig) and alkyl, aryl disubstituted I, excepting In, gave III. The bulky substituents present in the oxazole ring was found to give some marked effect on ring fission.
Hen egg white lysozyme was acetylated with acetic anhydride, the acetylated lysozyme was fractionated by carboxy methyl cellulose column chromatography, and three main peaks, termed F-I, F-II, and F-III, were obtained. The number of free amino groups in the acetylated lysozyme was determined by spectrophotometry using 2, 4, 6-trinitrobenzene-1-sulfonic acid. F-II and F-III possessed 4.6-4.8 unmodified amino groups per molecule and retained 7.5% of relative activity to Micrococcus lysodeikticus as compared to native lysozyme. Lysozyme moved faster than acetylated lysozyme to cathode in electrophoresis. In immunodiffusion, acetylated lysozyme (F-II and F-III) and lysozyme made a spur to antilysozyme serum. Quantitative precipitin reaction revealed that the antigenic determinants decreased by chemical modification. From these results, it may be concluded that acetylation of the amino groups alters the antigenic structure of lysozyme.
Conditions for nitration of 8-acetyl-7-hydroxy-4-methylcoumarin (I) was examined and a method for obtaining the 3-nitre (II) and 6-nitro (III) compounds together in a good yield was established. II and III were respectively converted to the 3-amino (IV) and 6-amino (V) compounds by catalytic reduction, and V was derived to the 6-acetamido compound (VII) by acetylation under a mild condition. VII underwent dehydrative cyclization on being heated with phosphorus pentoxide or polyphosphoric acid to 9-acetyl-2, 5-dimethyl-7-oxo-7H-pyrano[3, 2-f]benzoxazole (VIII), which forms a phenyl-hydrazone with its acetyl group was applied in 9-position. Nitration reaction of I to 6-acetyl-7-hydroxy-4-methylcoumarin (IX) and a method was established for obtaining the mononitro (X) and dinitro (XI) compounds at the same time in a good yield. Catalytic reduction of X and XI respectively afforded the monoamino (XII) and diamino (XIII) compounds. The above acetylation and oxazole cyclization of V were applied to XII and a similar reaction took place, forming 9-acetyl-2, 7-dimethyl-5-oxo-5H-pyrano-[2, 3-e]benzoxazole (XV) via its acetamido compound (XIV). XV also forms a phenyl-hydrazone like VIII. These facts suggest that the mononitro compound (X) obtained by nitration of IX is 6-acetyl-7-hydroxy-4-methyl-8-nitrocoumarin and the dinitro compound (XIII) is a 3, 8-dinitro derivative.
Two anthraquinone pigments, physcion and erythroglaucin, were isolated from the colored fraction of silica gel column chromatography for camelliagenin purification from the methanol extract of camellia oil cakes. However, infection of the oil cakes with Aspergillus ruber was demonstrated and the two pigments were proved to be present in the oil cake as the metabolic products of the fungus. It was pointed out that care must be taken in the treatment of such materials, especially when containing a rich amount of carbohydrates, for the infection with fungi.