Absorption, excretion, distribution, and metabolism of 2-(5H- benzopyrano [2, 3-b] pyridin-7-yl) propionic acid (Y-8004), a new anti-inflammatory agent, were investigated in rats and mice by the use of 14C-labeled compound (14C-Y-8004). When the radioactive compound was given to rats orally or intraperitoneally, about 50% of the given radio-activity (14C) was excreted in urine and 40% in feces during 72 hr, while about 80% in urine and 20% in feces after oral administration to mice. Approximately 55-60% was recovered in rat bile during 24 hr after oral administration. The highest blood level of 14C was obtained at 0.5-1 hr after oral administration to rats and mice. A good correlation was observed between blood level and dose level. However, apparent species difference in the blood 14C concentration and its disappearance rate were observed between rats and mice. When 14C-Y-8004 was orally administered to bileduct-cannulated rat, the blood 14C concentration and its disappearance rate came close to those of normal mice. The highest concentration of 14C was observed in the serum and relatively high levels in the liver and kidney of rats and mice after oral administration of 14C-Y-8004. In both animals, most of 14C in the serum existed as unchanged material bound to serum protein. Thin-layer chromatography after enzymic, acid, and alkaline hydrolysis experiments showed that the major metabolite in urine and bile of rats was Y-8004 acylglucuronide and in urine of mice Y-8004 acylglucoside. The present investigation provides the first evidence for the formation of an acylglucoside of a drug in mammals.
A new choleretic substance, capillarisin (I), was isolated from the herb of Artemisia capillaris Thunb. (Japanese name, "Inchinko" ?? 〓 ?? ) by tracing the activity in rats. By heating with 1% NaOH or H2SO4 in methanol, I was cleaved to p-hydroquinone and a compound (XI) or p-hydroquinone and the compound (XII). Infrared and ultraviolet spectra suggested that I and XI are chromone derivatives and XII is a coumarin derivative. Positions of the functional groups in XI and XII were determined by direct comparison with the synthetic samples, and the structure of I was established as 2-(p-hydroxy-phenoxy)-6-methoxy-5, 7-dihydroxychromone.
Four new 2-phenoxychromone derivatives were isolated from Artemisiae Capillaris Herba (Japanese name, "Inchinko" ?? 〓 ?? ). Their structures were established on the basis of chemical and spectroscopic evidences as 2-(p-methoxyphenoxy)-6-methoxy-5, 7-dihydroxychromone (4'-methylcapillarisin), 6, 7-dimethoxy-2-(p-hydroxyphenoxy)-5-hydroxychromone (7-methylcapillarisin) 2-(p-methoxyphenoxy)-5, 7-dihydroxychromone (6-demethoxy-4'-methylcapillarisin), and 2-(p-hydroxyphenoxy)-5, 7-dihydroxychromone (6-demethoxycapillarisin), respectively. Four flavonoids, cirsilineol, cirsimaritin, genkwanin, and rhamnocitrin, were also isolated from this herb.
In the oxidation reactions of 3-oxo-steroids with oxygen in a basic solution, the effect of various substituents in B and C rings was examined by product analyses and by ESR measurements. 3-Oxo-5α-steroids themselves produced only 2, 3-diketones although Δ3-semidiones were observed along with Δ2-semidiones in the ESR spectra. Introduction of 11-oxo, 11-methylene, 11β-methyl, Δ7 (8), or Δ9 (11) group into 3-oxo-5α-steroids gave 3, 4-diketones together with 2, 3-diketones, but the substituent effect of 11α-hydroxyl 11α-methyl-11β-hydroxyl, Δ9 (11)-11-methyl, Δ6 (7), Δ11 (12), Δ11 (12)-12-methyl, or 12-meth-ylene group was not observed significantly. 25D.5β-Spirostan-3-one (XLVIII) afforded only the 3, 4-diketone and no substituent effect was observed by introducing an oxo group into the C-11 position of (XLVIII). In the ESR measurements the concentrations of Δ2-semidiones and Δ3-semidiones changed with time and the ratios of the maximum concentration corresponded to the product ratios. The long range effect of these substituents can be interpreted in terms of"conformational transmission"based on the direction of enolation in the A rings.
Some aromatic hydrocarbons, such as benzene, toluene, ethylbenzene, p-xylene, and styrene, were polymerized by subjecting them to a radio-frequency glow discharge at a reduced pressure (plasma polymerization), resulting in any of three types of products : powder, oil, and solid film, under varied plasma conditions. The oily products soluble in chloroform and carbon tetrachloride exhibited an average molecular weight of 400-600. The infrared spectra of these materials showed similar characteristics and also similar to normal polystyrene having a linear backbone chain, whereas their nuclear magnetic resonance (NMR) spectra did not show resemblance to the latter. NMR spectra of these products showed the presence of aromatic protons, widely shifted aliphatic protons, and olefinic protons, and the comparison of signal intensities of the polymer products with that of monomers suggested the formation of aliphatic chains derived from the cleavage of the aromatic rings. Based on these spectral data, structure of the oily products is postulated to be a polystyrene type but to have longer and branched backbone chains involving some double bonds. By assuming 1.5 hydrogen atoms to be bonded to a chain carbon, as in the normal polystyrene, the number of backbone chain carbons per benzene ring should be about four. Values of H/C ratio calculated from this assumption agreed well with that obtained from elemental analysis.
Nitroanthranilic acids were reacted with picolinic acid, in the presence of phosphoryl chloride, to form 3-, 4-, and 5-nitro-2-picolinamidobenzoic acids which were used as the starting material for the application of anilines, with phosphorus trichloride as the condensation agent, to effect cyclization to 4 (3H)-quinazolinones. The yield of the cyclization product was very poor when the reaction was carried out with ortho-substituted anilines but the yield was raised 3-fold when polyphosphoric acid was used as the condensation agent. Examination of the nitration of 2-(2-pyridyl)-3-phenyl-4 (3H)-quinazolinone showed that the reaction progressed only with nitric acid in sulfuric acid to yield 2-(2-pyridyl)-3-(m-nitrophenyl)-6-nitro-4-(3H)-quinazolinone.
Studies were made on the intermolecular interaction of the oxazine dye Nile Blue A and calf-thymus deoxyribonucleic acid (DNA). It was concluded from these experimental results that two modes of interaction, ionic binding of the basic dye and the phosphate group of DNA, which leads to metachromasis of the dye, and intercalation of the dye between adjacent base-pairs of the macromolecule, are taking part in the binding of Nile Blue A and DNA : (1) When this dye was mixed with DNA at pH 7.0, intensity of its characteristic absorption bands (α and β bands) decreased, and new absorption bands appeared in the vicinity of 550 nm (γ band) and 668 nm (δ band). (2) The γ-band was produced when the molar ratio of [Dye]/[DNA-P] was greater than 1, while the δ-band was produced when this molar ratio was smaller than 1. (3) Flow dichroism spectrum of the δ-band indicated that the Nile Blue A molecule was oriented perpendicularly to the longer axis of the double helix of DNA ; dichroism was not observed with a mixture of this dye and heat-denatured DNA. (4) The γ absorption band was also produced by the mixed system of Nile Blue A and potassium poly (vinylsulfonate) : no spectral change was observed with a monomeric vinyl sulfonate. (5) Mixed systems of Nile Blue A and a high concentration of purine nucleosides or mononucleotides exhibited a larger δ band than the systems in which corresponding pyrimidine derivatives were involved. (6) Larger spectral changes were produced by the interaction systems of Nile Blue A and purine homopolynucleotides than by the systems in which pyrimidine homopolynucleotides were involved. (7) Viscosity and melting temperature of DNA increased with increasing concentration of this dye added.
Compaction of a powder has been simulated on two-dimensional model by employing a digital computer. In the process of formation of the initial bed, 400 discs of equal size were dropped one by one into a container, introducing the probability P to make each two discs cohere in contact. Compaction of the beds by tapping was also simulated by shifting each disc into the hole present in the lower layer. In this process the coordination number of a disc and the cohesion probability P'were taken into consideration. Another probability P"was introduced in the step of insertion of a disc into the hole created by the transfer of the former disc. The relation between porosity and tapping number was fitted in Kawakita's equation when P'was relatively large and P"small. On the other hand, Kuno's equation was applicable when P'was small and P"large. It was also indicated that the cohesion probability P'is closely related to the rate constant in these equations.
Methyl 2, 3-dideoxy-2, 3-dithio-α-D-altropyranoside derivatives were synthesized by the thermal rearrangement of xanthate derivative of methyl 4, 6-O-benzylidene-3-S-benzyl-3-deoxy-3-thio-α-D-altropyranoside (III) or methyl 4, 6-O-benzylidene-2-S-benzyl-2-deoxy-2-thio-α-D-altropyranoside (IV).
Photochemical reaction of 2-(1-cyclohexenyl) cyclohexanone (II) with formamide in tert-butanol afforded two cyclization products ; 1, 2, 3, 4, 4a, 7, 8, 9, 10, 10b-decahydro-6 (5H)-phenanthridinone (III) and 1, 2, 3, 4, 7, 8, 9, 10-octahydro-6 (5H)-phenanthridinone (IV). These two products (III and IV) were further dehydrogenated with sulfur to give the known compounds V and VI, respectively. On irradiation of 1, 2-cyclohexanedione (VIII) in acidic solution under various conditions, several dimerization products were obtained ; 4, 4', 5, 5', 6, 6'-hexahydro-2, 2'-dihydroxybiphenyl-3, 3'-dione (IX), perhydro-4a, -9a-epoxydibenzo-p-dioxin-5a, 10a-diol (X), perhydro-2, 3'; 2', 3-diepoxybiphenyl-2, 3, 3'-triol (XI), and an unknown compound (XII).
The base-catalysed reaction of 3-acetyltetramanilide (II) with benzaldehyde in refluxing ethanol gave two isomeric condensation products. This indicates that both the ring methylene group (5-position) and the methyl group in α-phenylaminoethylidene group of II have the possibility of being attacked by the benzaldehyde molecule. Ratio of their yield varied with the nature of the base, the basicity and the steric requirement. Differences in the selective catalytic action between pyridine and piperidine are discussed on the basis of the results on the catalytic H-D exchange rate of the CH bonds of II susceptible to the condensation reaction.
The four pigments of isatin derivatives were separated from the browinng reaction of L-ascorbic acid (AAH2) with p-toluidine. These colors were identified as 2, 3-di-(p-tolylimino)-5-methylindoline (I) (reddish brown), 2-deoxy-2-(p-tolylimino)-5, 5'-dimethyl-isoindigo (II) (reddish orange), 5, 5'-dimethylindirubin (III) (violet), and 3-deoxy-3-(p-tolylimino)-5, 5'-dimethylindirubin (IV) (violet), which were found to be formed by the reaction of glucose and p-toluidine. The formation pathway of these pigments is different from those produced by the glucose-p-toluidine reaction, that is, the reaction of 14C1-AAH2, 5, 6-isopropylidene-AAH2, 5-phenyl-2, 3, 4 (5) furantrione, glycolaldehyde, and triose reductone with p-toluidine suggested that they are not formed from C1-C2 fragment of AAH2, but formed from its C5-C6 fragment.
5α-Bromo-6, 19-epoxy-cholestan-3β-ol acetate was prepared in a good yield only by heating 5α-Bromo-cholestane-3β, 6β-diol 3-acetate in cyclohexane with I2-Pb (OAc)4 in the presence of calcium carbonate without ultraviolet ray irradiation.
Comparison between two-dimensional porosity εa and three-dimensional porosity εv was made by a computer simulation study. In the formation of beds based on a random packing model, circles and spheres of equal size were used for the two- and three-dimen-sional systems, respectively. The porosity parameter P was introduced to decide whether the circles or spheres cohere or not when they came into contact with each other. εa and εv for the same P values were then compared. Porosities from the two-and threedimensional regular packing model were also examined. Results obtained by the random packing model were in good agreement with those by the regular packing model, as well as the two-dimensional"open-beam"packing model.