A new eremophilane derivative, 8β-hydroxy-4β (H) 10β (H) 5α-eremophil-11-en-2-one (Tsuwabukinonol) was isolated from the rhizome of Ligularia tussilaginea MAKINO and its chemical structure was determined. Although the A/B ring junction of eremophilane derivatives from this plant has been reported as being only a cis-decaline type, it is very interesting that the A/B ring junction of this new compound was found to be a trans-decaline type.
The pharmacological effect of a methanolic extract of Swertia japonica, swertiamarin being the main secoiridoid glucoside of this herb and gentianine obtained from swertiamarin in aqueous ammonia, were investigated in mice and rats. Gentianine was found to exert depression of the central nervous system and anti-ulcerogenic action, as well as inhibitory action against gastric secretion, whereas the others had no appreciable action.
The effect of five nonsteroidal anti-inflammatory agents and seven sulfonamides on the binding of salicylic acid to bovine serum albumin (BSA, fraction V) was examined by the equilibrium dialysis method at pH 7.4 and 37°. Most of anti-inflammatory agents, which have a high affinity for BSA, strongly displaced salicylic acid. Sulfonamide derivatives also reduced the binding of salicylic acid though their effect of displacement was less than that of anti-inflammatory agents. When the percentage of displacement for salicylic acid was plotted against log (Σnk) which represents a binding ability of the displacing agent itself, a sigmoid curve was obtained. It was suggested that the amount of displacement tends to correspond to the binding ability of the displacing agent and becomes progressively greater as log (Σnk) becomes larger than that of salicylic acid. Furthermore, in the wide range of salicylic acid concentration (0.1-2.5×10-3M) naproxen and flurbiprofen showed patterns of displacement for salicylic acid different from that of other displacing agents. It was assumed that they have binding mechanisms different from the others including salicylic acid.
The polymeric forms of silicic acid in various aluminosilicate gels was investigated by the trimethylsilylation method. Aluminum silicate consists mainly of insoluble polysilicic acids. It also contains some anions, such as SiO44-, oligosilicic acids, and soluble polysilicic acids. On the other hand the aluminosilicate contains mainly anions, such as SiO44-, Si2O76-, Si3O108-, Si4O128-, and soluble polysilicic acids. It also contains some insoluble polysilicic acids. The molecular distribution of silicic acids in the aluminosilicate was the same as that of the original sodium silicate used in the synthesis. Soluble polysilicic acids were estimated to have a network molecular structure having a molecular formula of Si2nO5n+22 (n+2)-. The average degree of polymerization, 2n, was estimated to be 8.62-15.67.
Cannabis samples, more than 10 pieces each from nine administrative districts in Japan, were collected with soil for cultivation. The leaves of cannabis were picked and prepared in the usual way for irradiation and analyzed by the instrumental neutron activation method at Research Reactor Institute of Kyoto University. Concentration was determined for the following 35 elements : as Al, As, Au, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs, Cu, Dy, Eu, Fe, Gd, Hg, I, In, K, La, Lu, Mg, Mn, Na, Rb, Sb, Sc, Sm, Sr, Tb, Th, V, Yb, Zn. From this result, comparison of cannabis from various geographical origins in Japan from only the difference in element concentration and ratio of these elements was discussed qualitatively, and also the correlation of element concentration between cannabis leaves and the soil in which the plant is cultivated.
In order to find an efficient analgesic-antiinflammatory agent for chronic inflammatory diseases, synthesis of 3 (2H) pyridazinone derivatives (A, B, and C) with an acetic acid residue was carried out. In these compounds, the 4-position of 2-substituted 5-morpholino-3 (2H)-pyridazinones (4a, b, 5a, b, and 26) underwent electrophilic deuteration and also the 4-position of 5a and 26 was easily nitrated with nitric acid (d 1.50) at room temperature.
In order to develop an artificial kidney using encapsulated activated charcoal as the adsorbent, physicochemical properties of various kinds of charcoals prepared from different origins were examined. A spherical granule charcoal (mean diameter of 0.53±0.06 mm) from petroleum pitch, which has recently been developed by Kureha Chemical Co., Tokyo, was the most efficient in removing many kinds of solute, whose molecular weight is from 100 to 5000 daltons. Furthermore, the ash content and release of free particles by vibration were notably little compared to other charcoals of different origin, such as coconut, coal, coconut-coal and petroleum coke. By physicochemical tests on the petroleum pitch charcoal, it was proved to be satisfactorily safe for use as an adsorbent for an artificial kidney.
An acyloxycarboxylic acid (V), a new phenylpropanoid ester, anthriscusin (VI), and a phenylpropanoid ester (VII) were isolated from the roots of Anthriscus sylvestris HOFFM. (Umbelliferae), together with three kinds of known lignans, anthricin (I), isoanthricin (II) and 2-(3", 4", 5"-trimethoxybenzyl)-3-(3', 4'-methylenedioxybenzyl) butyrolactone (III), and a known phenylpropanoid, crocatone (IV). The structures of V and VI were elucidated respectively as (Z)-2-angeloyloxymethyl-2-butenoic acid and O-[(Z)-2-angeloyloxymethyl-2-butenoyl]-3-methoxy-4, 5-methylenedioxycinnamyl alcohol, and the structure of VII was presumed as 1-(3-methoxy-4, 5-methylenedioxyphenyl)-2-angeloyloxypropan-1-one on the basis of its spectral data.
Vapor-phase ammoxidation of 2-picoline, 3-picoline, 4-picoline, methylpyrazine, 2-methylpyrimidine, and 5-methylpyrimidine was studied over 1% Cr2O3-10% V2O5-pumice stone catalyst. Experiments were carried out in a flow reactor system at atmospheric pressure. By these reactions, nitriles were formed selectively and by-product formation was negligible. From kinetic analysis, experimental rate data were found to be well interpreted by the Langmuir-Hinshelwood mechanism, where the rate-determining step was the surface reaction between adsorbed picoline or methyldiazine and dissociatively adsorbed oxygen. The rate constants and apparent activation energies of these compounds were compared with π-electron density on ring carbon atoms bonded to the methyl groups, and with carbon-13 chemical shifts of methyl carbons. From these results, it was found that the reactivity of these compounds under ammoxidation conditions decreased with increasing electron density on the methyl carbon atoms.
Ammonolysis of 3, 4-dihydroisocoumarins to obtain 3, 4-dihydroisocarbostyrils was investigated. Heating of a solution of 8-deoxyphyllodulcin (3) or phyllodulcin (8), a 3, 4-dihydroisocoumarins having a phenyl group substituted at 3-position, in ethanolic ammonia gave the corresponding 3, 4-dihydroisocarbostyrils (1 or 2) and stilbenes (4 and 5 or 9). By the same reaction, agrimonolide (10) an 3-alkyl-3, 4-dihydroisocoumarins, gave only 3-alkyl-3, 4-dihydroisocarbostyril (11). Aminolysis of 3 with methylamine or N, N-dimethylaminoethylamine gave the corresponding 2-(2-N-alkylcarbamoylphenyl)-1-(3-hydroxy-4-methoxyphenyl) ethanols in a high yield, which gave the corresponding 2-alkyl-3, 4-dihydroisocarbostirils (14 or 15) by heating with 50% acetic acid containing 4% sulfuric acid.
Reaction of 2-methylquinoline 1-oxide (I1), 2, 4-dimethylquinoline 1-oxide (I2), 2-ethyl-3-methylquinoline 1-oxide (I3), and 6-methylphenanthridine 5-oxide (I4) with methanesulfonyl chloride, p-toluenesulfonyl chloride, p-toluenesulfonyl cyanide, or benzoyl chloride, in the presence of sodium p-toluenesulfinate, was carried out in acetonewater solution at room temperature. This reaction was found to progress in the four following types : 1) Introduction of a p-tolylsulfonyl group into the ring-carbon, accompanied by liberation of oxygen from the N→O group. 2) Introduction of a p-tolylsulfonyl group into the side-chain carbon in the position α to the ring-nitrogen, accompanied by liberation of oxygen from the N→O group. 3) Solely the liberation of oxygen from the N→O group. 4) When benzoyl chloride was used, benzoyloxyl group is introduced into the carbon atom in the methyl group in position α to the ring-nitrogen, accompanied by liberation of oxygen from the N→O group. However, present experimental data were insufficient to give conclusive evidence for conditions favoring the reaction noted in (2) above.
As one of studies on isolation of naturally occurring biologically active principles, antifungal constituents in the bark of Hibiscus syriacus L. were examined. Two active principles, oil (A), and (B), mp 156-157°, C14H8N2O, were isolated by a suitable combination of counter-current distribution and column chromatography. It was found that A was a mixture of lauric, myristic, and palmitic acid, and B was canthin-6-one (6H-indolo [3, 2, 1-d, e] [1, 5] naphthyridin-6-one).
Correlation between radioprotection by phenethylamine compounds and anoxia was examined from their action on the blood flow volume of femoral artery in a dog, blood pressure of common carotid artery in a rat, and isolated dorsal artery of a rat. It was found that radioprotection mechanism by vasoconstriction-anoxia was present in the phenethylamine-type and ephedrine-type compounds, while possible participation of anoxia was suggested in some of S-ephedrine-type and isothiourea-type compounds. In disulfide-type and thiosulfate-type compounds, mechanisms other than anoxia were considered to be present.
Examinations were made on the vapor-phase synthesis of 2-aminopyrimidine from trimethylenediamine and urethan, using the flow type reactor and with four types of a catalyst. This reaction afforded 2-aminopyrimidine, 2-methylpyrimidine, 2-ethylpyrimidine, and tetrahydro-2 (1H)-pyrimidinone. Effect of several reaction conditions on the yield of 2-aminopyrimidine was also examined. The maximum yield of 16% of 2-aminopyrimidine was obtained by reacting urethan and trimethylenediamine in a molar ratio of 5.3, using platinum catalyst on silica, at 400°, with W/F=22.4 g-cat. hr/mol. Some considerations were also made on this reaction mechanism.
Ac2-proteinase, one of proteinases of the venom of Agkistrodon acutus was purified by gel filtration on Sephadex G-75, followed by chromatographies on diethylaminoethyl (DEAE)-Sephadex A-50 and DE52 cellulose. By these procedures, 12.8 mg of purified preparation was obtained from 1g of crude venom. The purified preparation was homogeneous as judged by disc electrophoresis over polyacrylamide gel at pH 8.3 and isoelectric focusing. Ac2-proteinase also possessed both lethal and hemorrhagic activities. These and proteolytic activities were inhibited by ethylenediaminetetraacetic acid (EDTA), cysteine, or antiserum but not by soybean trypsin inhibitor or diisopropyl fluorophosphate. The molecular weight of Ac2-proteinase was estimated to be about 25000 by SDS-polyacrylamide gel electrophoresis, and the isoelectric point was found to be pH 4.9 by isoelectric focusing with carrier ampholyte. The minimum hemorrhagic dose, LD50, and proteolytic activities of the purified preparation were 0.431μg, 110μg/mouse, and 0.173 unit/mg, respectively. This protein did not contain any carbohydrates or nucleic acids.
In order to examine hemostatic activity, 5-alkoxy-4-hydroxy-2-methyl-3 (2H)-pyridazinones (V, VIa-d) and 4-substituted 2-methyl- or 2-phenyl-5-methylsulfonyl-3 (2H)-pyridazinones (XIa-f) were prepared. Among the compounds prepared, sodium 5-ethoxy-2-methyl-3-oxo-4-pyridazinolate (V), 4-hydroxy-2-methyl-5-methylsulfonyl-3 (2H)-pyridazinone (XIa), 4-(3-dimethylaminopropylamino)-2-methyl-5-methylsulfonyl-3 (2H)-pyridazinone (XIh), and 4-hydrazino-2-methyl-5-methylsulfonyl-3 (2H)-pyridazinone (XIj) showed activity for shortening the bleeding time comparable to carbazochrom sodium sulfonate (I).
Gas chromatographic retention indices of 67 kinds of purine and pyrimidine derivatives on nonpolar column (OV-1) and weakly polar column (OV-17) were collected. These results were applied to the hydrolysate of DNA and RNA, and their base components were analysed qualitatively. Some relationship between the retention index and chemical structure of purines and pyrimidines was considered.
Nine compounds were isolated from the leaves of Lespedeza cuneata G. DON (Leguminosae). β-Sitosterol, succinic acid, triacontan-1-ol, quercetin, kaempferol, pinitol, avicuralin, juglanin and trifolin were identified by comparison with the respective authentic samples. Additionally, assignment of the three flavonol-glycosides was confirmed by measurement of their 13C-NMR spectra.
Simultaneous determination of glycyrrhizin (G) and glycyrrhetic acid (GA) in plasma was established by high-speed liquid chromatography. G and GA were extracted from plasma with 0.25 N NH4OH·85% EtOH. The extracted sample containing indomethacin as an internal standard was analysed on a reverse-phase column (SC-02-250) with gradient elution from water to 0.5% acetic acid-90% acetonitrile.
Based on the previous observation that various rat ascites hepatoma cell lines showed different sensitivity to the new antitumor agent, bis (chloroalkyl) piperidine, and the possibility that this difference reflected the repair ability of the cells for damaged DNA, which might also be considered in the case of human cancer cells, the lethal action of 1-(β-chloroethyl)-2-chloromethylpiperidine hydrobromide (CAP-1) on colony-forming ability of the cells was examined using various human tissue cultured cell lines derived from tumor and normal tissues. The results of these experiments showed different effective concentrations for CAP-1 sensitivity of the cell lines at 37% (e-1) viability. The level of CAP-1 sensitivity of the cell lines agreed with their sensitivity to ultraviolet ray (UV) and nitrogen mustard N-oxide. It is well known that the level of UV-sensitivity reflects repair-ability of the cells, and DNA damage produced by alkylating agents may be repaired by the UV-repair (excision repair) mechanism, or at least by a mechanism sharing some of the same steps. Therefore, from these results and evidences, it may be concluded that the sensitivity of human cultured cell lines to chemicals is closely related to their repair ability.
Synthesis of 3-(tetrahydro-2-furanyl)-5-fluorouracil (3-Thf-FU) (III), which has been found to be a metabolic intermediate of 1, 3-bis (tetrahydro-2-furanyl)-5-fluorouracil (Thf2-FU) and an effective antitumor agent, is reported. 1-Alkane- or 1-arene-sulfonyl-5-fluorouracil (I) was trimethylsilylated by treatment with N, O-bis (trimethylsilyl) acetamide and treated with 2-acetoxytetrahydrofuran in the presence of stannic chloride to give 1-alkane- or 1-arene-sulfonyl-3-(tetrahydro-2-furanyl)-5-fluorouracil (II). III was obtained by deblocking of II with methanolic ammonia.
The novel fungal pigment, neocercosporin (I), C29H26O10, mp 237°, was isolated together with cercosporin (II) from Cercosporina Kikuchii nov. var. (MITTS-1 strain) as reddish violet orthorhombic crystals. The structure of I was elucidated as 5, 8-dihydroxy-2, 11-dimethoxy-1, 12-(2-hydroxypropyl)-6, 7-methylenedioxyperylene-3, 10-quinone. II was photosensitive and isomerized to isocercosporin (III) but I was stable and was not photosensitive.
Fluorophotometric method for the determination of dehydroepiandrosterone sulfate in urine has been established. The method involves the formation of an ion-pair complex between the sulfate and acridine orange, and extraction of the complex into 1, 2-dichloroethane, followed by the measurement of the fluorescence intensity at λex 495 nm and λem 520 nm. The limit of detection was about 80 ng/ml of dehydroepiandrosterone sulfate and the recovery from urine was between 92.3 and 103.3%. The present method has been applied to the determination of dehydroepiandrosterone sulfate present in normal human urine.
Compounds possessing a cyclic hydrazide structure in their molecule, 2-amino-3-phenyl-1 (2H)-isoquinolinone (I1), 3-amino-2-(4-methoxyphenyl)-4 (3H)-quinazolinone (II1), 5-amino-1, 5-dihydro-1-phenyl-4H-pyrazolo [3, 4-d] pyrimidin-4-one (III1), 5-amino-1, 5-dihydro-1-(2-pyridyl)-4H-pyrazolo [3, 4-d] pyrimidin-4-one (IV1), and 30 kinds of their derivatives were synthesized for antitumor screening. It was found that 5-(benzoylamino)-1, 5-dihydro-1-phenyl-4H-pyrazolo [3, 4-d] pyrimidin-4-one (III5) possessed an anti-tumor activity against Sarcoma-180A.
Effect of degassing on the nuclear magnetic relaxation time T1 of water in D2O-H2O mixture was examined. The degassing effect appears as the remarkable enhancement of T1 with an increase in the molar ratio (α), but appearance of a uniform degassing effect is found in the plots of 1/T1 to α, being independent of the values of α.
3-Aminonaphthostyril derivatives were synthesized from mercurinaphthalic anhydride, an acenaphthene derivative, by utilizing the reactivity of its carbon-mercury bond. Although an ergot-like physiological activity was anticipated in 3-aminonaphthostyril derivatives, there was no such activity. However, antibacterial tests revealed that the derivative having p-aminobenzenesulfonyl group substituted in the 3-amino group had an inhibitory action on tubercle bacilli.