Pure chloroform is known to be decomposed readily in the presence of air, even in the dark, although then very slowly, but in the absence of oxygen. In the first stage of the decomposition, chloroform produces an intermediate peroxide, Cl3COOH, which disapears in the second stage to yield chlorine, phosgene, and hydrochloric acid through two courses (a) and (b) as illustrated in chart 1.-1 The mechanism of phosgene formation was evidenced by the fact that decomposed chloroform produced diphenylurea by reaction with aniline and the reaction of the decomposed trichloroethylene or tetrachloroethane with aniline produced the same dichloroacetanilide, as shown in chart 1.-2 and 3 Ethanol added to the decomposed chloroform showed apparently a catalytic effect decomposing the peroxide to Cl2 or COCl2 through the courses shown by chart 1.-1-a and b Alcohols except methanol, ethers except dioxane, phenols, and hydrocarbons were useful as a stabilizer for chloroform, while acetone, acetic acid, ethyl acetate, and benzene were useless. In alcohols, the stabilizing effect became stronger with increasing number of carbon atoms in the molecule. It is interesting that hydrocarbons such as hexane and decane possess a marked effect as a stabi1izer. It is difficult to understand how the presence of so small an amount of stabilizer could prevent the decomposition of chloroform but it may not be unreasonable to assume the following : 1) It is considered that the stabilizers prevent the decomposition of chloroform in its primary stage, by the fact that a small amount or the stabilizer prevents the formation of even a trace of Cl- under conditions most favorable to decomposition : 2) The stabilizers containing hydrocarbons act as an anticatalyst in unchanged form, because they are so resistant to chemical change : and 3) The fact that various substances of different types such as alcohols, ethers, phenols, and hydrocarbons are useful as a stabilizer shows that the mechanism of this stabilization is not simple.
A thin-layer and gas-liquid chromatographic study has been carried out on the chemical constitutents of Bupleurum spp. Presence of three main saponins, named saikosides Ia, IB (Ib'), and II, was found in the methanolic extracts of Bupleurum spp. The chemotaxonomical differentiation of Bupleurum falcatum, B. longeradiatum, B. nipponicum var. yesoense, and B. triradiatum var. alpinum was discussed.
Protoporphyrin (IX) and its dimethyl ester were obtained in homogeneous polycrystals of high purity, in a good yield, from hemin by the modification of Ramsey's method. Purity and physicochemical properties of these crystals were confirmed by ultraviolet, infrared, and NMR spectra, differential thermal analysis, and X-ray power diffraction analysis. The dimethyl ester had hitherto been reported as melting at 223∼230°but differential thermal analysis showed that a part of the molecular structure and crystal form underwent change accompanied by heat evolution and, therefore, this temperature was found to be the decomposition point. There was also an endothermic phenomenon at 180°, with transition of the crystal phase.
Following isolation and structural determination of thalicarpine (I) and hernovine (II) from the formosan Hernandia ovigera L. (Japanese name "Hasunoha-girl"), *3, 1) a new aporphine-type base, hernangerine, was isolated from the phenolic portion of the same plant and its structure was found to be represented by formula III. Presence of L-reticuline (XIII) in this plant was also clarified.
L-Ascorbic acid and sodium L-ascorbate in vitamin C preparations were determined as trimethylsilyl derivative by gas chromatography. The stationary phase was 5% SE-52 (on silanized Celite 545, 60∼80 mesh) and column temperature was 210°. Determination was carried out by the peak area ratio method, using dibutyl sebacate as the internal standard. Results obtained by gas chromatography were in good agreement with those of iodometry.
Condensation of oxindoles (II) with carbon disulfide in tetrahydrofuran, using sodium hydride, and methylation of its products with dimethyl sulfate afforded 3-[bismethylthio)-methylene]oxindoles (IIIa-c)(Table I). The methylthio group in III underwent facile substitution with various amines and gave the corresponding monosubstituted derivatives (IVa-i)(Table II). Reaction of III with hydrazine hydrate or aniline resulted in facile substitution of two methylthio groups and afforded 1-methyl-3(dihydrazinomethylene) oxindole (V) and 3-(dianilinomethylene)oxindole (VII). Reaction of IVe and hydrazine hydrate gave 1-methyl-3-(hydrazinomorpholinomethylene) oxindole (VI). Reaction of III and ethanolamine gave 3-(oxazolidinylidene)oxindoles (VIII), and that of III and ethylenediamine gave 3-(imidazolidinylidene)-oxindoles (IX).
2'-Benzoyl-spiro(2-oxoindoline-3, 3'-oxyrans) (III)(Table I) were prepared by the application of hydrogen peroxide to 3-phenacylideneoxindoles (I). Reaction of III with hydrazine hydrate afforded 3'-pheny1-4'-hydroxy-spiro[2-oxoindoline-3, 4'-(2'-pyrazolines)](IV) (Table II). Dehydration of IV with saturated methanolic hydrochloric acid gave 3'-phenylspiro-[2-oxoindoline-3', 5'-pyrazoles](V) (Table III).
From the herbs of Youngia denticulata (Japanese name "Yakushi-so")(Compositae), germanicyl acetate (I), taraxasteryl acetate (II), germanicol (III), taraxasterol (IV), β-sitosterol (V), and 1-hexacosanol (VI) were isolated.
There have been found two types of ground ivy (Glechoma hederacea) (Labiatae), the fragrant and the non-fragrant one. The former has been found to contain a relatively large amount of monoterpenic ketones whose main component is l-pinocamphone. l-Menthone and l-pulegone have been isolated and presence of α-pinene, β-pinene, limonene, p-cymene, isomenthone, isopinocamphone, linalool, menthol, and α-terpineol has been detected. Composition of the essential oil has been found to vary according to the locality, season, and some other delicate factors. Besides the volatile constituents, ursolic acid, β-sitosterol, palmitic acid, and succinic acid have been identified. As the water-soluble components, proline, valine, tyrosine, aspartic acid, glutamic acid, threonine, serine, glycine, alanine, cystine, methionine, isoleucine, leucine, and phenylalanine have been detected and the former five amino acids have been isolated.
On heating with triethylammonium formate (5HCO2H·2NEt3) in the presence of Raney nickel catalyst, quinoline, isoquinoline, and acridine were smoothly reduced respectively to 3, 4-dihydro-1(2H)-quinolinecarboxaldehyde, 3, 4-dihydro-2(1H)-isoquinolinecarboxaldehyde ; and 9, 10-dihydroacridine in excellent yield.
2-Methyl(or cyclohexyl)-6-hydroxy-4(or 5)-chloro-3(2H)-pyridazinons (Vb, c and V'b, c) were synthesized by the condensation of chloromaleic anhydride and the corresponding hydrazine derivatives, and their structures were elucidated by chemical and physicochemical method. In order to examine their analgesic activity, 2-methyl(or cyclohexyl)-6-ethoxy-5(or 4)-dimethylamino-3(2H)-pyridazinone (Ib, c and I'b, c) were prepared from Vb, c and V'b, c. Among the compounds tested, Ib and I'b revealed about twice activity of that of aminopyrine.
The structure of anhydrotaxininol, C20H28O4, obtained by treatment of taxinine, a constituent of Taxus cuspidata SIEB. et ZUCC., with alcoholic sodium hydroxide, has been briefly reported in a preliminary communication.8) In this paper, details of experimental results and the discussion which led to the assignment of structure III to anhydrotaxininol are presented.
From the petroleum ether extracts of rhizomate of Alpinia speciosa K. SCHUMANN and A. kumatake MAKINO (A. formosana K. SCHUMANN), dihydro-5, 6-dehydrokawain (I) and 5, 6-dehydrokawain (II) were isolated. The latter was isolated for the first time from Zingiberaceae plants and the former, from a natural source.
Diethyl 3-(5-nitro-2-furyl)acryloylmalonate (I) was condensed with hydroxylamine hydrochloride and phenylhydrazine hydrochloride in ethanol to give ethyl 3-[2-(5-nitro-2-furyl)-vinyl)-5-oxo-2-isoxazoline-4-carboxylate (IIa) and ethyl 3-[2-(5-nitro-2-furyl)vinyl]-5-oxo-l-phenyl-2-pyrazoline-4-carboxylate (IIb). On the other hand, treatment of I with hydroxylamine hydrochloride-sodium acetate, hydrazine, hydrate, guanidine carbonate-acetic acid, and phenylhydrazine hydrochloride-sodium acetate in ethanol gave unexpected hydroxamate (IVa), hydrazide (IVb), and ethyl ester (IVc) of 3-(5-nitro-2-furyl)acrylic acid, and bis-phenylhydrazide (VI) of I, respectively. Antimicrobial activities of these compounds are listed.
In order to know whether carbamate N-glucuronides were metabolic end-products or not, the present experiment was carried out, using sodium meprobamate N-glucopyranosiduronate and urethan N-glucopyranosiduronic acid. It was found that β-glucuronidase prepared from rabbit liver did not act on these N-glucuronides in 0.1M acetate buffer at pH 4.4 to 5.6, and that most of the glucuronides administered intravenously into rabbits was recovered unchanged in the urine excreted within 24 hours.
Binding of Methyl Orange with α- and β-crystallins, the main proteins of lens cortex, was examined spectrophotometrically, in the range of pH 1.7∼8.0. Further, this binding at pH 3.6 was studied by the use of dialysis equilibrium method. As a result, the following points were clarified. 1) The binding of Methyl Orange with α- and β-crystallins in the range of pH 1.7∼8.0 occurs between the sulfone group in Methyl Orange and positively charged amino acid residue in the proteins. No difference was observed in the binding mechanism between the two proteins. 2) The number of binding sites of with Methyl Orange with the two proteins at pH 3.6 is smaller than that in the higher pH range. This fact is considered to be due to changes in the structure of the proteins at pH 3.6. 3) The binding of Methyl Orange with α-crystallin becomes the maximum at around pH 3.6, and that with β-crystalline is at around pH 3.2. This fact is considered to be due to the acid-type structure of Methyl Orange in the acid region, resulting in static repulsion of the positively charged molecule, and decoiling of the protein structure in the acid region.
The detailed investigation on the bases of Swertia japonica MAKINO was carried out. Extraction of the plant with chloroform using ammonia as usual gave, gentianine and a base of m.p. 129.5∼130°. The structure of the latter was now elucidated. On the other hand, however, the extraction with methanol in the absence of ammonia as well as the treatment with methylamine gave none of these compounds. Thus, an evidence that both substances must be the artifacts produced during the extraction process was presented.
The structure and configuration of litsericine, C17H21O3N, an alkaloid of the hexahydro-proaporphine type, was established as shown by formula (Ia) by direct comparison of the hexahydro derivative of mecambrine obtained by reduction. Litsericine has a methylenedioxy group in 1∼2 position, the absolute configuration of the asymmetric center takes the D(R) configuration, and the secondary alcoholic hydroxyl in the molecule takes an axial conformation. The fact that (-)-roemerine is a base belonging to the D(R) system was established by deriving this base to natural D(-)-nuciferine by the cleavage of the methylenedioxy group, followed by O-methylation. Some considerations were also made on the properties of the stereoisomers, V, XVI, and X VII, of N-methyllitsericine (II).
A glucuronic acid conjugate was isolated from the urine of rabbits receiving p-(methyl-amino)phenol by the lead acetate method and recrystallized from hydrous ethanol to colorless needles (I), m.p. 219°(decomp.), [α]<15>D-70°(H2O). The fact that hydrolysis of I with β-glucuronidase gave p-methylaminophenol and glucuronic acid, together with the results of elementary analysis, indicated that I was p-methylaminophenyl β-D-glucopyranosiduronic acid containing one-half molecule of water (C13H17O7N·1/2H2O). Synthetic evidence for the structure of I was provided by the fact that methylacetyl derivative obtained by methylation and acetylation of I was found to be identical with authentic methyl [p-(N-methylacetamido)phenyl 2, 3, 4-tri-O-acetyl-β-D-glucopyranosid]uronate prepared from p-(N-methylacetamido)phenol and methyl (2, 3, 4-tri-O-acetyl-α-D-gluco-pyranosylbromid)uronate by mixed m.p. and infrared spectra.
5-Benzyl-2-pyrrolidinone, which has a fundamental skeleton of both Amphetamine, a central nervous system stimulant, and γ-aminobutyric acid, a central nervous system depressant, was synthesized in order to examine its pharmacological action.
By using ultraviolet and infrared spectral determination of n- hexane infusions, the presence of polyacetylenic compounds was clarified in Acanthopanax sciadophylloides, Kalopanax septemlobus (Araliaceae), Torilis japonica, Osmorhiza aristata var. montana, Pimpinella koreana, Bupleurm longiradiatum. Oenanthe javanica, Seseli ugoensis, Pleurospermum austricum, Glehnia littoralis, Conioselinum chinense. Angelica deculsiva, A. miqueliana, A. polymorpha, and A. edulis (Umbelliferae).
In relation to the study on the metabolic fate of carbamate N-glucuronides, pharmacological actions of meprobamate and urethan N-glucuronides were examined comparing with those of carbamates themselves. Neither competition to convulsant action of strychnine nor prolongation of hypnotic action of pentobarbital was observed in both N-glucuronides, but was found in carbamates themselves. It was demonstrated, however, that both N-glucuronides were distributed considerably well into the brain.