α-(3-Methoxy-4-benzyloxybenzylidene)-β-(3′, 4′-dimethoxybenzylidene)-succinic acid was prepared by the Claisen reaction from ethyl succinate, and reduced with Na-amalgam from which two racemates were isolated. One was crystalline and was resolved as strychnine salts to d- and l-dicarboxylic acids. The anhydride (d) of the l-acid was led to a butyrolactone with Al-amalgam and a mixture of l-arctigenin and its isomer, l-α-(3, 4-dimethoxybenzyl)-β-(3′-methoxy-4′-hydroxybenzyl)-butyrolactone, was obtained as an oil. Their separation, however, was not successful. Application of dimethyl sulfate to this oily mixture yielded methyl ether of l-arctigenin as crystals which were found to be identical with the derivative obtained from natural l-arctigenin.
l-α- (3-Methoxy-4-hydroxybenzyl) -β- (3′, 4′-dimethoxybenzyl) -succinic acid (XIV), m.p. 188°, [α]D-16.8°, undergoes transition by acetic anhydride to an oil of d-form (XIV′) that fails to give a strychnine salt, which seems to show that it is a diastereoisomer different from the d-type antipode of (XIV). Treatment of the ethyl ester of (XIV′) with sodium alcoxide results in its reversion to the crystals of (XIV). This has clearly shown that (XIV) is a trans-l-type compound that is formed by similar mechanism as the transition of cis-hexahydrophthalic acid to a trans-type and of cis-acid ester to trans-type reported by Hückel, and transition of trans-1, 2, 3, 4-tetrahydronaphthalene-2, 3-dicarboxylic acid to cis-anhydride and of cis-ester to trans-acid reported by Haworth. In the synthesis of arctigenin, it is assumed that the trans-l-type of (XIV) first forms cis-d-anhydride which is reduced by Al-amalgam to cis-d-butyrolactone which undergoes another transition to a trans-l-type by the action of sodium alcoxide or alcoholic sodium hydroxide.
Several asymmetric cyanines (IX-XIX) were obtained by reacting quinaldine ethiodide or 2-methylbenzothiazole methiodide (ethiodide) in acetic anhydride with orthothio-formic ester and trimethine cyanines (I-VIII) containing quinoline, benzothiazole or benzoxazole nucleus. Several symmetric neocyanines (XX-XXII) were prepared by reacting orthoformic ester and acetic anhydride respectively with 2, 4-dimethylthiazole isoamiodide (allobromide) and 6-bromoquinaldine ethiodide.
Chloroacetylamino compounds were prepared by reacting chloroacetyl chloride on aminoquinolines, condensation of diethylamine to the former compounds furnishing eight derivatives possessing diethylaminoacetylamino group in the 5-, 6-, 7- and 8-positions of quinoline nucleus.
It was clarified that the application of acetyl chloride to 3-methyl- or 3-methoxy-diphenyl ether in the presence of aluminum chloride results in the introduction of the acetyl radical in the ortho position of the methyl or the methoxyl group. In the case of 4-methoxy-4′-methyldiphenyl ether, the reaction. occurs chiefly in the ortho position of the methoxyl radical but a small amount of crystals of m.p. 142-144° and reddish purple crystals of m.p. 209-211° were also obtained structures of which are still unknown.
In order to obtain π-iodo-dl-camphor (II) from π-bromo-dl-camphor (I) by halogen substitution, iodides were applied to (I) in alcohol and acetone solvents but (II) could not be obtained. However, (II) was obtained in a good yield by the same reaction in acetic acid medium. The same reaction was applied on π-chloro-, α-chloro-π-bromo-and α, π-dibromo-d-camphors by which iodine substitution was respectively effected in the π-position. In this case, the halogen in the α-position is not affected at all. These π-iodo-camphors are all new compounds, their physical constants being as follows: m.p. [α]D Oxime, m.p. Oxime, [α]D π-Iodo-dl-camphor 79° [α]D148° Oxime, [α]D π-Iodo-d-camphor 56° +133.5° 110° Oxime, [α]D4° α-Chloro-π-iodo-d-camphor 136° +89.5° 110° Oxime, [α]D4° α-Bromo-π-iodo-d-camphor 159° +101.1° 110° Oxime, [α]D4°
An allied compound of chloramphenicol was prepared in which the nitro group in the para position of the benzene nucleus has been substituted with cyano group. This new compound effectively inhibited the growth of Salmonella typhi (0901 strain) in a dilution of 5×10-4.
An allied compound of chloramphenicol was prepared in which the nitro group in the benzene nucleus has been substituted with a hydroxyl group in the para and meta positions. No effective action was found to be exerted by this compound against Salmonella typhi.
Nagai and Kanao converted dl-N-benzoyl-norephedrine through the oxazoline into the diastereoisomeric dl-N-benzoylnorisoephedrine. This oxazoline inversion can be utilized to convert dl-erythro-1-phenyl-2-acetamido-1, 3-propanediol (V) into the dl-threo compound (IX). The erythro compound forms 2-methyl-4-hydroxymethyl-5-phenyl-Δ2-trans-oxazoline (VII) by treatment with thionyl chloride and sodium carbonate. On treatment with diluted mineral acids, the oxazoline (VII) gives O-acetyl compound (VIII) which can be rearranged to dl-threo-1-phenyl-2-acetamido-1, 3-propanediol (IX) with ammonia.
Some fatty acids have been employed in the anodic synthesis previously described but chaulmoogric acid and similar compounds have not been prepared by this means. The present authors obtained 10-(2-dimethyl-3-methyl-3-cyclopentenyl)-capric acid, which has a structure similar to that of chaulmoogric acid, by the electrolysis of a mixture of α-camphorenic acid and ethyl sebacate in diluted ethanol solution.
α, β-Dihydroxy-α, α-dianisylbutane was obtained by the reaction of p-methoxybenzoyl-ethyl carbinol and 4-methoxyphenylmagnesium bromide. By distillation under reduced pressure or treatment in 30% sulfuric acid with heating, the former gave α, α-dianisyl-β-butanone. Treatment of β-hydroxy-α, β-dianisyl-α-ethylbutane with phosphorylchloride with heating yielded 4, 4′-dimethoxy-α, β-diethylstilbene.
In order to be used for the synthesis of benzesterol, β-anisyl-α-ethylvaleric acid was prepared as follows: Condensation of anisaldehyde and ethyl malonate yielded ethyl anisalmalonate to which was applied ethylmagnesium iodide to effect 1, 4-addition to obtain ethyl α-anisylpropylmalonate, followed by the application of sodium and ethyl iodide to yield ethyl α-anisylpropylethylmalonate. The hydrolysis and decarboxylation of the latter yielded the objective compound.
p-Toluenesulfo-β-anilinopropionic acid and its esters are unstable against alkalis.p-Toluenesulfo-β-anilinopropionic acid and methyl p-toluenesulfo-β-anilinopropionate were decomposed by the respective action of caustic alkali solution and alkali alcoxide to yield p-toluenesulfanilide.
The macro- and microscopic features of the rhizomes and stipes of several ferns containing phloroglucide were studied. Pharmacognostic studies and the important differences, such as the number of sclerenchymatic layers, are also discussed.
Anthelmintic actions of 18 kinds of arylthiourea compounds synthesized were examined using earth worms. 2-Carbethoxyphenylthiourea showed remarkable insecticidal action similar to that of hexylresorcinol used as the control. 4-Carbethoxyphenylthiourea and 2-carbethoxyphenylurea, both possessing similar structure as above, did not show any apparent anthelmintic action. Similar anthelmintic actions were also shown by ethyl anthranilate and ethyl.N-acetylanthranilate as that of 2-carbethoxyphenylthiourea.
The method of Pew [J. Am. Chem. Soc., 70, 303 (1948)] for the reduction of quercetin with sodium carbonate and hydrosulfite was examined and it was found that an improvement could be effected by the addition of 2 moles of boric acid to 1 mole of quercetin in order to retain solubility of quercetin during reduction. By this improvement, betterment of the yield and purity is obtained of the reduction product, distylin (3, 3′, 4′, 5, 7-pentahydroxyflavanone), m.p. 230-232° (acetate, m.p. 154-155°), giving positive zinc-hydrochloric acid reaction. The same reaction was carried out on myricetin by which the improved method was found to give better yield and quality of the reduction product, ampeloptin (3, 3′, 4′, 5, 5′, 7-hexahydroxyflavanone), m.p. 239-241° (acetate, m.p. 170-172°), giving positive zinc-hydrochloric acid reaction.
During the cold extraction of rutin from the Chinese crude drug, Flos Sophorae japonicae, with aqueous solution of borax, it was found that extraction at5-10° yielded rutin while that at 37° yielded quercetin. Pretreatment of the drug by heating at 80-85° for 3 hours resulted in the yield of rutin even by extraction at 37°. The cold extract of Flos Sophorae japonicae was then applied to rutin at 37° by which quercetin was obtained. The same treatment with solution of rutin by the addition of borax gave quercetin from rutin. This decomposition does not occur if the cold extract of the drug is applied at 5-10° or heated at 100° for one hour. Examination of the sugars obtained by the decomposition showed them to be glucose and rhamnose but no rutinose was detected. From these results, it has been clarified that a group of glucosidase is present in Flos Sophorae japonicae which decomposes rutin to quercetin, glucose and rhamnose, the enzymatic reaction of which is not obstructed by the presence of an excessive amount of borax.
As an example of the application of cold extraction using aqueous solution of borax, extraction of myricitrin from the bark of Myrica rubra Sieb. et Zucc. was carried out. The raw material was first heated at 80° for one hour and the extraction yielded crystals of m.p. 193-194° (decomp.). Acid decomposition of the product yielded myricetin and rhamnose which proved the crystals to be those of myricitrin. The yield was 5.5% which was far inferior to that of 7.5% obtained by warm methanol extraction. Warm methanol extraction of the heartwood gave myricitrin in 0.19% yield. Presence of ampeloptin, the flavanone corresponding to myricetin, was not detected either in the bark or in the heartwood.
As a result of the comparison between solubilization tests using aqueous solution of borax and reduction coloration using magnesium and hydrochloric acid in flavones and flavonols, it was found that in order to effect the former reaction it would be necessary for the presence of hydroxyl groups in a certain position of flavones and flavonols while the latter reaction necessitated the presence of a certain number of hydroxyls or methoxyls. In this respect, the mechanism of these two reactions was found to be fundamentally different. Results of the reduction coloration by magnesium or zinc and hydrochloric acid carried out on various flavonoids are shown in Table I. Tables II to VII show individual results on these flavonoids. As shown in Table VIII, there is a distinct difference between flavonols and flavonol-3-glucosides, although coloration by magnesium and hydrochloric acid is the same in both cases. Flavonols do not color with zinc and hydrochloric acid but flavonol-3-glucosides color red by it. The same is true, as shown in Table IX, of those compounds in which methyl group is attached to the hydroxyl in 3-position, instead of the sugar residue. These observations offer useful means for the distinction between flavonol-3-glycosides and flavonols.
It was concluded from the experiments conducted that the by-product obtained in the Pschorr cyclization of 2-aminopiperonoyl-N-benzylaniline and 2-aminobenzoyl-N-benzyl-p-phenetidine is the dimer formed by condensation, with liberation of nitrogen, at the amino group of the original material which undergoes diazotization.
In order to obtain antihistaminics of ethylene diamine type possessing a pyrazolone nucleus, 4-benzylaminoantipyrine and dimethylaminoethyl chloride hydrochloride were reacted in alcohol in the presence of alkali carbonate by which 4-(N-benzyl-N-dimethylaminoethyl)-aminoantipyrine hydrochloride, m.p. 216-217°, was obtained.
Syntheses of 2-benzylaminopyrimidines possessing halogen in the 4-, 5- and 6-position of the pyrimidine portion were carried out, following being obtained: 5-Chloro-2-benzylaminopyrimidine, m.p. 130-132°; 5-bromo-2-benzylaminopyrimidine, m.p. 134-136°; 5-chloro-2-(p-methoxybenzylamino)-pyrimidine, m.p. 128-139°; 5-bromo-2-(p-methoxybenzylamino)-pyrimidine, m.p. 142-145°; 4-chloro-2-benzylaminopyrimidine, m.p. 93-94°; 4, 6-dichloro-2-benzylaminopyrimidine, m.p. 130-132°; 4-chloro-6-methyl-2-benzylaminopyrimidine, m.p. 133-136°.
2-Benzylaminopyrimidine (IV) can be obtained in a good yield by the catalytic reduction of benzylidene-2, 2′-dipyrimidylamine (I), p-methoxybenzylidene-2, 2′-dipyrimidylamine (II) or furfurylidene-2, 2′-dipyrimidylamine (III) in caustic soda alkalinity with benzyl alcohol as the solvent. The same reduction of (I) with anise alcohol as a solvent yields 2-p-methoxybenzylaminopyrimidine (V). Heating of (II) and (III) in benzyl alcohol with caustic soda gives (IV), while heating of (I) in anise alcohol with caustic soda gives (V) in a good yield.
Condensation of 2-ethyl-4-amino-5-aminomethylpyrimidine (VI) with γ-aceto-γ-chloropropyl acetate (IV) or its alcohol (X), in the presence of carbon disulfide and ammonia, respectively yields α-aceto-γ-acetoxypropyl N-[2-ethyl-4-aminopyrimidyl (5)]-methyldithiocarbamate (VII) or α-aceto-γ-hydroxypropyl N-[2-ethyl-4-aminopyrimidyl (5)]-methyldithiocarbamate (XI). Both (VIII) and (XI) give 3-[2′-ethyl-4′-aminopyrimidyl (5′)]-methyl-4-methyl-5-β-hydroxyethylthiothiazolone (2) (VIII) by heating their respective solution in diluted hydrochloric acid. Heating their respcetive caustic alkali solution or heating their crystals to above their decomposition points results in the formation of 2-thio-7-ethyl-1, 2, 3, 4-tetrahydropyrimido-(4·5-d)-pyrimidine (IX). Oxidation of (VIII) with hydrogen peroxide in acid medium, followed by treatment with barium chloride gives, with a good yield, 3-[2′-ethyl-4′-aminopyrimidyl (5′)]-methyl-4-methyl-5-β-hydroxyethylthiazolium chloride hydrochloride (XVIII). Acetylation of (VIII) with acetic anhydride an pyridine yields 3-[2′-ethyl-4′-aminopyrimidyl (5′)]-methyl-4-methyl-5-β-acetoxyethylthiothiazolone (2). Use of 2-benzyl-4-amino-5-aminomethylpyrimidine (XII) in place of 2-ethyl-4-amino-5-aminomethylpyrimidine (VI) allows similar reactions to proceed.
Condensation of 2-methyl-4-hydroxy-5-aminomethylpyrimidine (X) and γ-aceto-γ-chloropropyl acetate (II), in the presence of carbon disulfide and ammonia, results in the formation of α-aceto-γ-acetoxypropyl N-[2-methyl-4-hydroxypyrimidyl (5)]-methyl-dithiocarbamate (XI) which, when dissolved in diluted hydrochloric acid and heated, changes to 3-[2′-methyl-4′-hydroxypyrimidyl (5′)]-methyl-4-methyl-5-β-hydroxyethylthiothiazolone (2) (XII). Heating the crystals of (XI) to around its decomposition point changes it to 3-[2′-methyl-4′-hydroxypyrimidyl (5′)]-methyl-4-methyl-5-β-acetoxyethylthiothiazolone (2) (XIII). Heating alcoholic or methanolic solution of (XI) with caustic alkali yields the O-ethyl (XVI) or O-methyl ester (XVIII) of N-[2-methyl-4-hydroxypyrimidyl (5)]-methylthiocarbamic acid. (X) is obtained by heating caustic alkali solution of (XI). Oxidation of (XII) with hydrogen peroxide in acid medium, followed by treatment with barium chloride, gives 3-[2′-methyl-4′-hydroxypyrimidyl (5′)]-methyl-4-methyl-5-β-hydroxyethylthiazolium chloride hydrochloride (XV).
Heating a solution of α-aceto-γ-hydroxypropyl N-[2-methyl-4-hydroxypyrimidyl (5) ]-methyldithiocarbamate (XI) in hydrochloric acid, or heating of its crystals near its decomposition point changes it to 3-[2′-methyl-4′-hydroxypyrimidyl (5′) ]-methyl-4-methyl-5-β-hydroxyethylthiothiazolone (2) (VI). Application of caustic alkali in alcoholic or methanolic solution of (XI) gives the O-ethyl (XVIII) or O-methyl ester (IX) of N-[2-methyl-4-hydroxypyrimidyl (5) ]-methylthiocarbamic acid, and heating of its aqueous solution with caustic alkali gives 2-methyl-4-hydroxy-5-aminomethyl-pyrimidine (X). Condensation of ammonium N-[2-methyl-4-aminopyrimidyl (5) ]-methyldithiocarbamate (XIII) with methyl iodide yields ethyl N-[2-methyl-4-aminopyrimidyl (5) ]-methyldithiocarbamate (XII) which, when treated with caustic alkali or by heating, decomposes to form 2-thio-7-methyl-1, 2, 3, 4-tetrahydropyrimido-(4, 5-d)-pyrimidine (XIV). Boiling the hydrochloric acid solution of (XII) for a long period of time gives ethyl N-[2-methyl-4-hydroxypyrimidyl (5)]-methyldithiocarbamate (XV) and (X).
Condensation of valeroamidine (II) and ethoxymethylene malondinitrile (III) or of valeroimino ether (V) and aminomethylene malondinitrile (VI) yields 2-butyl-4-amino-5-cyanopyrimidine (IV), electrolytic reduction of which, using palladium-black as the cathode, results in the formation of 2-butyl-4-amino-5-aminomethylpyrimidine (VII). Condensantion of (VII) with γ-aceto-γ-chloropropyl alcohol (VIII), in the presence of carbon disulfide and ammonia, gives α-aceto-γ-hydroxypropyl N-[2-butyl-4-aminopyri-midyl (5)]-methyldithiocarbamate (IX) which, when treated with caustic alkali, changes to 2-thio-7-butyl-1, 2, 3, 4-tetrahydropyrimido- (4.5-d) -pyrimidine (X), but heating the diluted hydrochloric acid solution of (IX) results in the formation of 3-[2′-butyl-4′-aminopyrimidyl (5′)]-methyl-4-methyl-5-β-hydroxyethylthiothiazolone (2) (XI). Oxidation of (XI) with hydrogen peroxide in acid medium, followed by treatment with barium chloride yields 3-[2′-butyl-4′-aminopyrimidyl (5′)]-methyl-4-methyl-5-β-hydroxyethyl-thiazolium chloride hydrochloride (1).
Condensation of 2-methyl-4-amino-5-aminomethylpyrimidine (VII), γ-aceto-γ-chloropropyl acetate (VIII) and carbon oxysulfide in the presence of ammonia, or of ammonium N-[2-methyl-4-aminopyrimidyl(5)]-methyl-thiocarbamate (X) and (VIII), results in the formation of S-(α-aceto-γ-acetoxypropyl) N-[2-methyl-4-aminopyrimidyl(5)]-methylthiocarbamate (IX). The same condensation of (VII), γ-aceto-γ-chloropropyl alcohol (XII) and carbon oxysulfide yields S-(α-aceto-γ-hydroxypropyl) N-[2-methyl-4-aminopyrimidyl-(5)]-methylthiocarbamate (XIII). Solvation of (IX) and (XIII) in diluted hydrochloric acid and its heating give 3-[2′-methyl-4′-aminopyrimidyl-(5′)]-methyl-4-methyl-5-β-hydroxyethyl-thiazolone (2) (III). When (IX) and (XIII) are heated around its decomposition point or treated with caustic alkali, thay yield 2-oxo-7-methyl-1, 2, 3, 4-tetrahydropyrimido-(4, 5-d)-pyrimidine (XI). Compound (III) thus obtained is identical with the substance of m.p. 233-234° obtained from “Aneurindisulfid” (VI) by Zima and the others. (III) does not easily convert to thiochrome (IV).
Ultraviolet absorption spectra of 13 kinds of 2-aminothiodiazole derivatives were examined. A certain amount of determination can be made from these absorption curves as to whether these compounds take aminothiodiazole structure or thiodiazolone imide structure.
Acylation of thiosemicarbazide with acid chloride in acetone in the presence of sodium bicarbonate or an excessive amount of thiosemicarbazide or in pyridine gives acylthio-semicarbazide, the treatment of which with concentrated sulfuric acid yields 2-amino-thiodiazole derivatives possessing a substituent in the 5-position. The acid chloride used were acetyl, propionyl, butyryl, benzoyl, p-nitrobenzoyl and phenylacetyl chlorides.
By the respective condensation of the potassium salts of phenol, nitrophenols and chlorophenols to 2, 3-dichloro-5-nitropyridine in alcohol, eight kinds of phenyl (nitrophenyl or chlorophenyl)-3′-chloro-5′-nitropyridyl-(2′) ethers were obtained, the reduction of which yielded the corresponding phenyl (aminophenyl or chlorophenyl)-3′-chloro-5′-aminopyridyl-(2′) ethers. 2-Hydroxy-3-chloro-5-nitropyridine was obtained by the chlorination of 2-hydroxy-5-nitropyridine, treatment of which with a mixture of phosphorus pentachloride and phosphoryl chloride yielded 2, 3-dichloro-5-nitropyridine. The latter yielded 2-methoxy-3-chloro-and 2-ethoxy-3-chloro-5-nitropyridines. Deëthylation. of the latter yields 2-hydroxy-3-chloro-5-nitropyridine.
1) Oxidation of 2-amino-5-chloro (or bromo) pyridine in sulfuric acid solution with hydrogen peroxide gives 2-nitro-5-chloro (or bromo) pyridine in a good yield. This method applied on 2-amino-5-iodopyridine results in its decomposition with liberation of iodine. 2) Application of sodium phenoxide to 2-nitro-5-chloro (or bromo) pyridine in alcoholic solution does not result in the formation of phenyl pyridyl ethers. On the contrary, application of sodium thiophenoxide under the same conditions results in the formation of phenyl pyridyl-(5) thioethers. Application of sodium alcoxides results in the formation of 2-alcoxy-5-chloro (or bromo) pyridines. 3) Application of sodium ethylmercaptide to 2-nitro-5-bromopyridine in alcohol or benzene solution results in the formation of 2-amino-5-bromopyridine.
Cleavage of 3, 4-methylenedioxy-6-methyldiphenyl ether (V) with metallic sodium in liquid ammonia results in the formation of 4-hydroxy-6-methyldiphenyl ether (VI), the excessive use of metallic sodium being ineffective in the bisection of the ether linkage forming the diphenyl ethers. The same cleavage of o-, m- and P-hydroxydiphenyl ethers is also obstructed in the cleavage of ether linkage by the presence of phenolic hydroxyl group.
Qualitative estimation was made of the direction of the cleavage of ether-linked oxygen in 1-phenoxynaphthalene (I), 2-phenoxynaphthalene (II), 1, 1′-dinaphthyl ether (III), 1, 2′-dinaphthyl ether (IV) and 2, 2′-dinaphthyl ether (V) by the application of metallic sodium in liquid ammonia. As a result, (I) and (II) were both cleaved to phenol and naphthalene, or benzene and naphthol, but such cleavage did not proceed with (III), (IV) and (V), majority of these reaction products forming resinous substances.
Constant gas current for carbon and hydrogen determination was obtained by the use of an improved apparatus, especially by the use of a novel-designed three-way stop cock and gas holder, together with the Mariotte flask. The total volume of the current passed is measured by the passage of time thus simplifying the whole apparatus and eliminating complex series of operations.
(2-Hydroxy-3-ketocyclohexyl)-acetic lactone (IV), needed for the synthesis of nor-(11)-santonin can be prepared by approximately the same method as for α-(2-hydroxy-3-ketocyclohexyl)-propionic lactone described in the IVth Report, i.e. the double bond of [cyclohexene-(2)-yl]-malonic acid (VII), is hydroxylated by potassium permanganate or organic peracid to form a lactone between the hydroxyl group in the C2-position and the carboxyl in the side-chain. The hydroxyl in the 3-position is then oxidized with chromic acid and decarboxylated to the objective compound obtained as crystals of m.p. 50° [semicarbazone, m.p. 201° (decomp.)]. This method can also be used for the preparation of esters and nitriles corresponding to (VII). As was shown in the IVth Report, various isomers of the intermediate compounds are obtained.
A new compound, p-sulfamylbenzyl alcohol, was prepared by the reaction of p-sulfamylbenzylamine and nitrous acid. The same compound was obtained from p-sulfamylbenzaldehyde by the Cannizzaro reaction, thus confirming its structure. The antibacterial tests of this compound was, made against Staphylococcus aureus and Escherichia coli.
1) Two non-pathogenic soil bacteria, strains “KT1” and “KT3, ” were found to have a property of hydrolyzing hippuric acid, benzoyl-DL-α-aminobutyric acid and benzoyl-DL-phenylalanine. 2) A stock laboratory strain of Staphylococcus aureus Terashima and a strain of Staphylococcus isolated from bubo were both able to hydrolyze hippuric acid and benzoyl-DL-α-aminobutyric acid but not benzoyl-DL-phenylalanine. 3) From the experiments with hippuric acid and benzoyl-DL-phenylalanine, it may at least be said that Escherichia coli and Proteus OX 19 are quite inactive. 4) On the other hand, two strains of Penicillium, “NRRL 1978 B2” and “176 Yabuta, ” are also able to liberate benzoic acid from either of the above-mentioned N-benzoylated amino acids.
It was demonstrated that Mycobacterium phlei is capable of hydrolyzing hippuric acid, benzoyl-DL-α-aminobutyric acid, benzoyl-DL-phenylalanine, dibenzoyl-L-cystine, phenaceturic acid, laurylglycine and lauryl-DL-phenylalanine. It should be noted that lauryl-DL-phenylalanine is much more easily hydrolyzed by organisms than benzoyl-DL-phenylalanine.
An aqueous solution of the crude glycoside obtained from the leaves (or roots) of Rhodea japonica Roth. was consecutively extracted with chloroform and a mixture of chloroform and alcohol, and the two extracts were passed through a chromatographic column of active alumina. After developing with hydrous alcohol, different kinds of crystalline glycosides were obtained from respective extracts. Chloroform extract yielded a cardiotonic glycoside, rhodexin B, C29H44O9, m.p. 262° (decomp.) (corr.), [α]D25: -39.5° (ethanol), and the chloroform-alcohol extract, rhodexin A, C29H44O9⋅2H2O, m.p. 265° (decomp.) (corr.), [α]D10: -20° (ethanol). Presence of two other glycosides was assumed from the paper chromatogram of the crude glycosides, whose isolation is being studied.
Rhodexin A resists hydrolysis under mild conditions but submits to hydrolysis with diluted alcohol containing 3.4% of hydrochloric acid to yield β-anhydrorhodexigenin A, identical with α-anhydrosarmentogenin. The sugar obtained by the hydrolysis of rhodexin A was found to be rhamnose from paper partition chromatogram and the phenylosazone. Since rhodexin A yields an iso compound with negative Legal reaction by the action of alkali, it was assumed to possess a tertiary hydroxyl group in C14-position. From these results, rhodexin A is assumed to be a glycoside composed of sarmentogenin as an aglycone and rhamnose as its sugar.
From the results obtained in the previous report (v.s.), the aglycone of rhodexin A is assumed to be sarmentogenin whose isolation from rhodexin A was successfully carried out by the Mannich method. Hydrolysis of rhodexin B with diluted alcohol containing 3.3% of hydrochloric acid yielded dianhydrorhodexigenin B which coincides with dianhydrogitoxigenin. The sugar obtained by the hydrolysis of rhodexin B was found to be rhamnose from its paper partition chromatogram and the phenylosazone. From these results, rhodexin B is assumed to be a new glycoside possessing gitoxigenin as an aglycone and rhamnose as its sugar.
The structure of α- and β- anhydrorhodexigenin A was assumed to be as follows, from its absorption spectrum, coloration reaction and chemical behavior: β-anhydrorhodexigenin A possesses a double bond between C14 and C15, and its α-isomer is one of the following: 1) Unsaturated between C15 and C16; 2) Unsaturated between C14 and C15, with reverse steric configuration of C8 from the β-isomer; 3) Unsaturated in C5-6 or C6-7 in the B ring.
In spite of the report that Nargund and the others succeeded in total synthesis of santonin, Clemo and the others countered that the formation of its intermediate, α-(2-hydroxy-3-ketocyclohexyl)-propionic lactone (V), was not possible, and the present authors also confirmed that such could not be formed by the Paranjape method. In order to find a new synthetic procedure, the authors carried out the following reaction. The double bond of α-(cyclohexen-(2)-yl)-propionic acid (XI) was hydroxylated to allow formation of a lactone ring between the hydroxyl group in C2 and the carboxyl group in the side-chain, and the hydroxyl in the C3-position was oxidized to a carbonyl with chromic acid by which (V) was successfully obtained. Similar hydroxylation of (cyclohexen-(2)-yl)-methylmalonic acid (X) with permanganate or organic peracid results in lactonization and subsequent oxidation of the hydroxyl in 3-position and decarboxylation, or decarboxylation followed by oxidation, also gives (V). This synthetic procedure can also be applied to the esters or amides corresponding to the acids of (X) and (XI). Of the four possible isomers of (V), one kind of racemate was obtained as crystals of m.p. 87°, while the other two were obtained as oily substances. The semicarbazone described by Paranjape, et al., is different from the semicarbazones of any of the above three racemates.
dl-1-(4′-Phenoxybenzyl)-6, 7-methylenedioxy-1, 2, 3, 4-tetrahydroisoquinoline (V) and dl-1-(4′-phenoxybenzyl)-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline (VI) were prepared from 4-phenoxyphenylacetyl chloride with 3, 4-methylenedioxyphenylethylamine and 3, 4-dimethoxyphenylethylamine, respectively.
1) An examination was made on a new synthetic method of obtaining N1-acylsulfanilamides in good yields by the fusion of a mixture of phenyl carboxylate, sulfanilamide and alkali carbonate, or phenyl carboxylate and an alkali salt of sulfanilamide. 2) The reaction mechanism of the double melting point that is sometimes seen in N1-acylsulfanilamides and N1-acylmetanilamides was examined.
1) Nitration of 2-amino-5-chloropyridine at 55° with sulfuric and nitric acids (1 mol. HNO3) gives 2-amino-3-nitro-5-chloropyridine, while the application of 2 moles or more of nitric acid at 55-60° gives 2-hydroxy-3-nitro-5-chloropyrldlne. 2) Treatment of 2-amino-3-nitro-5-chloropyridine with sulfuric and nitric acids at 0° to 5° gives 2-nitramino-3-nitro-5-mchloropyridine which is affected by sulfuric acid at 60-65° to revert to 2-amino-3-nitro-5-chloropyridine. Further application of sulfuric and nitric acids to 2-nitramino-3-nitro-5-chloropyyridine at 55-60° changes it to 2-hydroxy-3-nitro-5-chloropyridine which gives a 2, 5-dichloro-3-nitropyrldine by chlorination with a mixture of phosphoryl chloride and phosphorus pentachloride. 3) Application of sodium methoxide to 2, 5-dichloro-3-nitropyridine gives 2-methoxy-3-nitro-5-chloropyridine, and of potassium phenoxides yields phenyl pyridyl ethers containing a nitro group. Reduction of the ethers gives corresponding amino compounds.
1) By treating 2-amino-6-methylpyridine with sulfuric and nitric acids, 2-amino-3-nitro- and 2-amino-5-nitro-6-methylpyridines were obtained, with a by-product of 2-hydroxy-5-nitro-6-methylpyridine. 2) 2-Amino-5-nitro-6-methylpyridine was diazotized to 2-hydroxy-5-nitro-6-methylpyridine which was chlorinated with phosphoryl chloride and phosphorus pentachloride to 2-chloro-5-nitro-6-methylpyridine. 3) By the application of the potassium salts of phenols to 2-chloro-5-nitro-6-methyl pyridine, phenyl pyridyl ethers containing nitro group were prepared, the reduction of ethers yielding corresponding amino compounds.
In order to examine their efficacy as diuretics, following suberic acid derivatives were prepared: α, α′-dibromo-, α, α′-dichloro-, α, α′-diiodo-, α, α′-dihydroxy-, α, α′-diureido-, α, α′-diphenylureldo-, α, α′-diphenoxy-, α, α′-dialkylmercaptosuberic acids and -suberocolic acids.
Growth inhibitory action in vitro against Mycobacterium tuberculosis (Aviann type A 67 strain) was tested with 24 kinds of arylthiourea synthesized. Of these tested, 2-hydroxy-, 2-amino- and a new compound 2, 6-dihydroxyphenylthiourea showed a remarkable inhibitory power about the same as or a little better than that of tibione used as a control, which seems to show that arylthiourea possessing a hydroxyl or an amino group in the ortho position shows a strong growth inhibition. The minimum concentration at which growth is inhibited with human type tubercie bacilli (H2 strain) is similar to that against avian type bacilli. No noticeable effect was found with in vitro growth inhibition test of these compounds against Staphylococcus aureus (Terashima strain) and Escherichia Coll.