To study the compression characteristics of powders, 0.15-3.0 g of potassium chloride powder (42-65 mesh) was poured into the cylindrical die of 8.02 am inside diameter, and compressed from one side by the upper punch under a constant upper punch pressure (about 1000 kg/cm2 in the maximum). After compressing for 10 min, the thickness of powder bed and the lower punch force were measured. . By Janssen's theory, where the ratio K of the horizontal to the vertical pressure and the coefficient μ of friction on the die wall are regarded as constant, the ratio PL/PU of the lower to the upper punch pressure should increase monotonously with the decrease of the thickness of powder bed at the constant diameter of powder bed. When a constant weight if potassium chloride powder was compressed, the ratio PL/PU varied complicatedly with the increase of upper punch pressure. These functions were determined from the assumption of K and μ as the functions of pressure, and from the comparison of the pressure-porosity relationship in hydrostatic compaction with that in die compaction. Using these functions, partial revision of Janssen's equation Was made.
The lysate of the amebocytes (the pre-gel), which reacts specifically with endotoxin to form gelation reaction, was extracted from Japanese horseshoe crab (Tachypleus tridetatus). The pre-gels, which were prepared by extracting the amobocytes of Japanese horseshoe crab in aqueous solution with N-ethylmaleinimide as anti-aggregating agent showed the sensitivity of 1/100 of the pre-gels prepared from American horseshoe crab (Limulus polyphmus) in gelation reaction to endotoxin, and the active pre-gels were obtained from 30% of an individual of Japanese horseshoe crab. The specific reactivity of the pre-gels to endotoxin was observed, but the pre-gels did not show reaction with any substance from a living body such as amino acids ; peptides, proteins, saccharides, lipids, nucleic acids and related substances, and amines, and therefore, high specificity was recognized. The gelation reaction showed a parallel correlation with the pyrogenic activity of endotoxin and detoxification of endotoxin with alkaline treatment.
An examination was made on anti-aggregating agents of amebocytes for preparing further sensitive pre-gels from Japanese horseshoe crab (Tachypleus tridentatus). Twelve kinds of known anti-aggregating agents for blood platelets and/or amebocytes were selected, and their anti-aggregating activities at the time of taking blood from Japanese horseshoe crab and sensitivities of the pre-gels prepared with them were examined. It was recognized that methylxanthine derivatives such as theophylline, caffeine, and theobromine, were better than the known anti-aggregating agents. The sensitivity of the pre-gels prepared by using theophylline as an anti-aggregating agent was similar to those of the pre-gels prepared from American horseshoe crab (Limulus polyphemus), and there was a possibility for practical use of the pre-gel for the detection of endotoxin. Whenever the pre-gels were prepared by using the new anti-aggregating agent, the pre-gets having higher sensitivity was obtained from the individual of Japanese horseshoe crab in a yield higher than 70%. The gelation reaction of the new pre-gets was correlated with the pyrogenic activity of each of several endotoxins, but some points remained in doubt The occurrence of gelation reaction was recognized in a pH range of 5.50 to 7.75, but the optimum pH of the reaction was within a range 6.50 to 6.75. The gelation reaction was affected by the concentration of a salt. The activity of the pre-gel was stable even under lyophilized condition, and activity of the lyophilized powder was durable for a long period at different temperatures.
1-Arylbutadiene was obtained when 1-aryl-1-acetoxy-3-butene was flashed through a quartz tube at 500-900°; at a higher temperature range, the Cope reaction occurred to give a cyclized compound (III) and its dehydrogenated product (IV). Pyrolysis of 4-pyridyl derivative (Id) at 830° gave quinoline (20%) besides isoquinoline. Similarly, 2-quinolyl derivative (Ie, 670°) afforded benzo [f] quinoline (10%) along with the normal products (IIe and IIIe). Formation of quinoline and benzo [f] quinoline must presumably involve 10- and 14-membered ring intermediates, respectively. Thus the total energies of 10 isomers expected to arise from 10- and 14-membered ring intermediates were calculated by the ω-method.
Fifteen compounds (Table I) were isolated from the xylem of root of Xanthoxylum arnottianum MAXIM. (Japanese name "Iwa-zansho"). Base I (9), mp 210°, was assumed to be des-N-methylchelerythrine. Four were known coumarins ; marmesin (19), suberosin (8), osthenol (21), and 7-demethylsuberosin (23). Two new coumarins were confirmed to be rutaretin methyl ether (25), which was already known as a methylated product of a natural phenolic coumarin, rutaretin (24), and (R)-(-)-columbianetin (28), the antipode of the known (S)-(+)-columbianetin. Isolation of both products from a natural source is for the first time. Three other new coumarins, arnottinin (26), C14H14O4, mp 191-193°; arnottianol (12), C15H16O4, mp 119-121°; and xanthoarnol (27), C14H14O5, mp 208-209°, were characterized. Two lignans, l-asarinin (7) and syringaresinol (31), β-sitosterol (2), and palmitic acid (1) were recognized. A new sesquiterpene, sesquiterpene-I (4), C15H26O, mp 80°, was assumed to have a cadinane or a guaiane skeleton from its nuclear magnetic resonance spectral data.
Four alkaloids, 11 coumarins ; and 2 neutral components were isolated from the xylem of the stem of Xanthoxylum arnottianum MAXIM. (Japanese name "Iwa-zansho"). Three of the alkaloids were confirmed with the known furoquinoline alkaloids, dictamnine (11), robustine (15), and haplopine (19). A new water-soluble quaternary base, Base II, was isolated as its picrate, C11H16O2N+·C6H2O7N3-, mp 256-260°, which was assumed to be a simple N, N-dimethyltetrahydroisoquinolinium derivative from its molecular formula. In order to compare the physical constants, 6, 7-dihydroxy-(23), mp 242-244°, and 7, 8-dihydroxy-2, 2-dimethyl-1, 2, 3, 4-tetrahydroisoquinolinium picrate (24), mp 181 -184°, were synthesized. Five coumarins, (R)-(-)-columbianetin (4), marmesin (5), rutaretin methyl ether (9), osthenol (8) and arnottinin (10), and β-sitosterol (1) and l-asarinin (2) were obtained as common consituents in the root of the same plant together with two other known coumarins, xanthyletin (3) and psoralen (18), as sole components of the stem. Peucedanol methyl ether (14), a methylated product of naturally occurring peucedanol, was isolated for the first time from a natural source. Three other new coumarins, arnottianin (12), C15H16O5, mp 197 -198°; coumarin I (6), C14H10O3, mp 180-183°, and coumarin II (7), C15H12O4, mp 140-145°, were characterized.
Metabolism of 6-methyl-2-thiouracil was studied in rats by using 14C-labeled compound. Following the oral administration of 6-methyl-2-thiouracil [2-14C] (490 mg/kg), the about 68% of the administered radioactivity was excreted in urine, 27% in feces, and 1.2% in respiratory CO2 within 72 hr. After oral ingestion of the radioactive compound, radioactive substances excreted in urine after 48 hr were 6-methyl-2-thiouracil, 6-methyl-uracil, 6-methyl-2-methylthiouracil, 6-methyl-4-oxo-pyrimidine, 2-amino-6-methyl-4-oxopyrimidine, and urea which were present in about 46.2, 9.1, 1.6, 1.8, 0.2, and 0.8% of total radioactivity in the urine, respectively. In in vitro tests using rat liver slices, radioactivity was also detected in 5, 6-dihydro-6-methyluracil along with the above metabolites.
Taraxasteryl palmitate (I), taraxasteryl acetate (II), and taraxasterol (III) were isolated and identified from the ether extract of the flowers and the methanol extract of the leaves of Eupatorium fortunei TURCZ. (Compositae). I, II, and III were also isolated from the methanol extract of the leaves of E. chinense L. var. simplicifolium (MAKINO) KITAM., E. chinense L. subsp. sachadinense (FR. SCHM.) KITAM., and E. lindleyanum DC. Fumaric acid, succinic acid, and mannitol were isolated and identified from the leaves and stems of E. fortunei. Euparin was detected from the methanol extract of the roots of E. fortunei and E. lindleyanum, but not from the roots of E. chinense var. simplicifolium and H. chinense subsp. sachalinense.
3-Monosubstituted oxindole (4) was converted to 3, 3-disubstituted 1-acetyl-oxindole (1') by acetylation with boiling acetic anhydride followed by alkylation with sodium hydride and alkyl halide in refluxing tetrahydrofuran. The product was saponified in ethanolic potassium hydroxide to 3, 3-disubstituted oxindole (1). 1 was reduced with lithium aluminum hydride or sodium dihydro-bis (2-methoxyethoxy) aluminate to 3, 3-disubstituted indoline (2). To convert the indolines (2) thus obtained to the 3H-indoles (3) ; various oxidizing agents were examined. As a result, dehydrogenation by refluxing with activated manganese dioxide in anhydrous toluene was found to be generally useful for this purpose.
Some 1, 3-disubstituted 1, 2, 3, 4-tetrahydro-β-carboline derivatives were synthesized by the Pictet-Spengler reaction with DL-tryptophan methyl ester and aldehydes. They were separated into their stereoisomers by alumina column chromatography, and their configuration (cis and trans) was examined from their nuclear magnetic resonance spectra and those of their acetates. By the application of the above result, azoninoindole derivatives (11 and 12) were synthesized.
On the basis of the previous findings, relationship between the structure and appearance of sweet taste was examined by synthesis of 3-hydroxy-4-methoxybenzylaniline (III), which is the structural conversion product of β-(3-hydroxy-4-methoxyphenyl)ethylbenzene (I), by application of the theory of bioisosterism, III had a fairly sweet taste while N-ethyl-3-hydroxy-4-methoxybenzylaniline tasted bitter. modification of III molecule with a propyl group, which is considered to be equivalent with phenyl group, was then carried out based on the theory of lipophilic equivalent, and the synthesized 3- hydroxy-4-methoxybenzylpropylamine was found to be tasteless. An attempt was made to clarify the relationship between the chemical structure and sweet taste of these series of compounds on the basis of these facts.
The chemical components of pollen grains of Ambrosic elatior L. examined and the following compounds were identified ; hydrocarbons, α-and β-amyrin, α-amyrin acetate, seven fatty acids, β-sitosterol, and campesterol. Among these, some of such fatty acids, β-sitosterol, and campesterol were found as form of glyceride. Ambrosic acid, eighteen amino acids, citric acid, and fructose were identified as water-soluble components.
Pollen grains of Alnus japonica STEUD. were treated with supersonic waves in an organic solvent, their chemical components were examined, and the following compounds, hydrocarbons, lupenone, and β-sitosterol were identified. As water-soluble components, seventeen amino acids, malonic acid, glucose, and mannose were identified. From the acetone extracts, a new flavone glucoside ; quercetin 3-β-D-glucopyranosyl-4-O-α-D-glucopyranoside (1), was isolated and its structure was elucidated from chemical evidences and spectroscopic data.
pH dependence of binding properties of mitomycin derivatives to bovine serum albumin and some transport behaviors of mitonmycin derivatives aqueous solution through cellophane tube, were investigated in order to clarify the relationship between the chemical structure of mitomycin derivatives and their binding sites. As previous paper, investigated mitomycin derivatives were demethoxymitomycin-A, 7-amino-N-methylisomitomycin-B, mitomycin-C, decarbamoylmitomycin-C, and 10-acetoxydecarbamoylmitomycin-C. 1) Mitomycin derivatives are more labilized in acidic condition than in alkaline, and are relatively stable in the pH region of 6.0 to 10.0. Among these compounds, mitomycin-C is the most stable in the above pH range. 2) Diffusion coefficients of mitomycin derivatives at 25° in 0.05 M aqueous phosphate and borate buffer range from 0.3×10 to 0.4×10-5(cm2/sea), and it is found that transport processes of mitomycin derivatives through a cellophane tube are rate-determined by diffusion processes. 3) The Scatchard plot showed that mitomycin derivatives bind to bovine serum albumin at homogenous binding sites with 9 saturated binding sites at pH 8.0 as well as at pH 7.0. Association constants at pH 8.0 decrease to 1/1.6 to 1/3.3 times compared with these at pH 7.0, and especially marked decrease in association constants was observed for decarbamoylmitomycin-C and 10-acetoxydecarbamoylmitomycin-C.
Crystalline inorganic components important for identifying plants, such as oxalates, cystoliths, and silicon bodies, have not been isolated from plants in pure state and detailed examination of their composition has not been made as yet. It has now become possible, through the development of the "low-temperature plasma ashing method for plant tissues, " to separate crystalline inorganic components from plants, easily and entirely without change in their chemical composition from the evidence of perfect coincidence of X-ray powder diffraction patterns between the crystals in original and ashed specimens. In the present series of work, the separated crystalline inorganic components were submitted to X-ray powder diffraction, thermal analysis, measurement of infrared absorption spectra, and elemental analysis. As a result of concerted examination of these analytical data, it was found that when the crystals in the plant consist of calcium oxalate, they always have the composition of calcium oxalate monohydrate Ca (COO)2·H2O, irrespective of isolated, aggregate, or needle crystals. The cystolith was found to have the composition of calcium carbonate CaCO3 by X-ray powder diffraction diagram, with reference to standard CaCO3 and elemental analysis showed that cystolith is a pure CaCO3. The silicon body has the composition of silicon dioxide SiO2 its crystal structure being amorphous in the majority, as in fused quartz, mixed with a minute amount of crystalline α-quartz.
A number of compounds related to ethyl 2-(4'-chlorophenoxy) isobutyrate (clofibrate) were synthesized for the purpose of preparing hypolipidemic agents. These included 3-tert-butyl-4-hydroxyanisole and other miscellaneous derivatives in addition to 2-(4'-chlorophenoxy) isobutyryloxybenzoates. The preparations, hypolipidemic activity, and toxicity of these compounds are discussed. Ethyl 2-[2'-(4"-chlorophenoxy) isobutyryloxy] benzoate (7), butyl 2-[2'-(4"-chlorophenoxy) isobutyryloxy] benzoate (9), and ethyl 4-[2'-(4"-chlorophenoxy) isobutyryloxy] benzoate (23) possessed good combiation or hypolipidemic activity and toxicity.
Mono-, bis-, and tris-O-(substituted phenoxyacetyl) inosines were prepared and assayed for hypolipidemic activities in rats. Analyses of their proton magnetic resonance spectra led to the assignment of C-proton on the ribose ring. In particular, the structure of 3', 5'-O-bis [α-(p-chlorophenoxy) isobutyryl] inosine was confirmed by the shift of C3'-and C5'-proton to a lower magnetic field.
The following four species of Liliaceae were examined for long-chain aldehyde, alcohol, and ketone composition by gas chromatography and mass spectrometry : Smilax china L. (leaves, stems, and roots), Polygonatum odoratum D. (leaves), Tulipa gesneriana L. (bulbs), and Scilla japonica B. (seeds). The first two species were found to contain C25-C32 aldehydes, mainly octacosanal. All except Scilla japonica B. (seeds) contained C24, C26, C28, and C30 primary alcohol, and Smilax china L. contained 16-hentriacontanone in leaves and stems.
Improvement in amidation of lysergic acid was examined. Amidation with triphenyl-phosphite-imidazole-hexamethylphosphorylamide and with hexamethylphosphorylamide-tosylchloride gave a marked high total yield with little epimerization. Especially, the latter method has an advantage for preparation of monoalkylamides with maintainance of the configuration at C8-position of the starting material.
Three kinds of amino acids, L-valine, L-alanine, and L-isoleucine and three kinds of alcohol, 1-eicosanol, 1-docosanol, and 1-tetracosanol were isolated from the terestrial parts if Oenanthe javanica (BLUME) DC. Besides these components β-sitosterol and C15-C29 normal saturated hydrocarbons were confirmed by gas chromatography-mass spectrum spectrometry.