The major metabolite in urine of mice, treated orally with 2-(5H- benzopyrano [2, 3-b] pyridin-7-yl) propionic acid (Y-8004), a new anti-inflammatory agent, was isolated by preparative thin-layer chromatography after acetylation with pyridine-acetic anhydride. The results of mass, infrared, and nuclear magnetic resonance spectra were compared with those of an authentic sample, and the major metabolite was identified as Y-8004 acylglucoside. Unchanged Y-8004, and methyl and acetyl derivatives of Y-8004 acylglucuronide, minor components in mouse urine, were also isolated and identified by similar methods.
Total synthesis of yokonoside, 2'-carboxy-4', 5-dihydroxy-2-β-D-glucopyranosyloxybenzanilide (1b), isolated from Aconitum japonicum THUNB., was carried out by two different routes. The 4'-deoxy analog (1a) was also synthesized. The Koenigs-Knorr reaction of 5-benzyloxy-2-hydroxy-2'-methoxycarbonylbenzanilide (5a) with silver carbonate gave a dimer, 2, 3'-bis (2-methoxycarbonylphenylcarbamoyl)-4, 5'-dibenzyloxy-2'-hydroxydiphenyl ether (7a), as a by-product.
In order to examine anticholinergic activity of pyrrolidines analogous to 1, 1-diethyl-3-diphenylmethylene-2-methylpyrrolidinium bromide (Prifinium Bromide), cis- and trans-1, 1, 5-trimethyl-2-ethyl-, and cis- and trans-1, 1, 2, 4, 5-pentamethyl-3-diphenylmethylenepyrrolidinium iodides were synthesized. Results of their pharmacological activity were also reported.
Aliphatic compounds of Erythronium japonicum DECNE were fractionated by anion exchange resin column chromatography, using nonaqueous media, and qualitatively and quantitatively determined by gas-liquid chromatography and mass spectrometry. On this method, fatty acid methyl esters were found in the leaves and fruits. Fruits and flowers contained 10-heptacosanol, leaves contained 10-nonacosanol, and stems contained both 10-heptacosanol and 10-nonacosanol.
Acid azides (IV) have been prepared by the reaction of (E)- and (Z)-alkenoic acids (IIa-d) with diphenyl phosphorazidate. The isocyanates (V) formed by the rearrangement of IV were converted to (E)- and (Z)-alkenylureas (Ia-b) by the addition of ammonia. It was found that (Z)-acid chloride ((Z)-III) isomerized to (E)-III by heat, (Z)-IVa, c, d isomerized to (E)-IVa, c, d in the presence of triethylamine, and (E)-Va was polymerized to a trimer (VI) by the catalysis of triethylamine, triethylphosphine, and pyridine.
Reaction of quinoline 1-oxides, possessing alkyl or phenyl group in 2 or 2 and 3 positions, with benzoyl chloride and potassium cyanide was carried out. Substituents in the quinoline 1-oxides used were the following 13 ; 2, 4-tetramethylene (Ia), 2, 3-trimethylene (Ib), 2, 3-dimethyl (Ic), 2-ethyl-3-methyl (Id), 2-methyl (Ie), 2-propyl (If), 2-isobutyl (Ig), 2-isopropyl (Ih), 2-phenyl (Ii), 3-methyl-2-phenyl (Ij), 2-phenyl-3-propyl (Ik), 2, 3-diphenyl (II), and 3-bromo-2-phenyl (Im), and the results may be summarized as follows : 1) When the reaction is carried out in aqueous solution, tetrahydroquinoline derivatives with introduction of -OH (-OCH3 when reacted in methanol) into 2-position, [chemical formula]into 3-position, and -CN into 4-position are formed, accompanied by deoxygenation of N→O group. Such derivatives are not formed from Ie, Ii, and Im. 2) When there is an alkyl group in 2-position, derivatives with [chemical formula] introduced into the carbon atom α to the alkyl group are also formed, accompanied by deoxygenation of N→O group. 3) When the original compound contains a phenyl group in 2-position, derivatives with [chemical formula] introduced into 6- or 8-position are also formed, accompanied with deoxygenation of N→O group. When the reaction is carried out in methanol, -OCH3 group is introduced into 6-position in the case of Ib and Ii. This reaction was attempted with 2-furoyl chloride, p-anisoyl chloride, nicotinoyl chloride, and p-nitrobenzoyl chloride as the acid chloride. There was no especially notable effect of the electronic effect of electron-donating or -attracting group in these acid chlorides on the reaction results.
In addition to β-sitosterol, a new tannin was separated and named "lagertannin" from the leaves of Lagerstroemia speciosa (L.) PERS. It's chemical structure was clarified as 3, 4-di-O-methyl-4'-O-β-D-glucosylellagic acid. Stigmasterol, campesterol, and five kinds of olefins were identified by gas chromatography.
Reactions of trialkylborane with amides were examined and the action of trialkylborane as Lewis acid was observed in these reactions. Reaction of trialkylboranes (I and II) with aromatic primary amides (III to V), without a solvent and at a high temperature, gave the corresponding nitriles (VII to IX). In the reaction with benzamide (III), 2, 4, 6-triphenyl-1, 3, 5-triazine (VI) was obtained with benzonitrile (VII). The same reaction with aromatic secondary amides (X to XV) afforded the corresponding amidine derivatives (XVI to XXI).
Six capsaicinoids were synthesized ; homocapsaicin, norcapsaicin (IV), N-(4-hydroxy-3-methoxybenzyl)-6-methyl-hept-trans-4-enamide (V), homodihydrocapsaicin, nordihydrocapsaicin, and N-(4-hydroxy-3-methoxybenzyl)-6-methylheptamide (VI), among which IV, V, and VI are new compounds. Their acid parts were synthesized in a good yield by the one-step method, i.e., anodic synthesis introduced by Linstead, et al. Infrared, nuclear magnetic resonance, and mass spectra of six capsaicinoids were examined.
Dehydrogenocyclization of trimethylenediamine and aldehyde to 2-alkylpyrimidine was studied on platinum group metal-Al2O3 catalysts in the streams of water vapor and hydrogen gas. In a flow system, the reaction was carried out between 290° and 410°, at atmospheric pressure. The optimum temperature range was 340-380° for 9 kinds of alkehydes used. On a Pt-Rh-Al2O3 catalyst and in a molar ratio aldehyde/trimethylenediamine of 1.2, 2-alkylpyrimidine was obtained in a good yield (30-50%) without the decay of catalyst activity. From kinetic studies, the reaction mechanism was considered as follows : Homogeneous rapid reaction of trimethylenediamine and aldehyde yielded 2-alkylhexahydropyrimidine, which, on a catalyst, was immediately dehydrogenated to 2-alkyl-1, 4, 5, 6-tetrahydropyrimidine. Dehydrogenation of 2-alkyl-1, 4, 5, 6-tetrahydropyrimidine to 2-alkylpyrimidine was the rate-determining step and followed the first-order kinetics. As the alkyl group became bulkier, the rate of formation and the final yield of 2-alkylpyrimidine decreased.
In carrageenin-induced peritonitis in rats, 2-(5Hbenzopyrano[2, 3-b]pyridin-7-yl)-propionic acid (Y-8004) given orally inhibited significantly both protein exudation and leucocyte accumulation. This agent also accelerated the absorption of peritoneal fluids in prophylactic experiments, as well as the decrease of peritioneal fluids, exudative protein, and leucocyte counts in therapeutic experiments. The free activity and its ratio of lysosomal enzymes such as aryl sulfatase were found to increase markedly in the peritoneal fluids of rats with carrageenin plus zymosan-induced peritonitis. The increment may be due to the release from emigrated leucocytes during phagocytosis of zymosan. Y-8004 not only inhibited the increment but also showed the same effect on the above indexes in therapeutic experiments. These effects were also observed in the oral treatment with indomethacin, phenylbutazone, or ibuprofen. These results suggest that Y-8004 and anti-inflammatory agents used have an inhibitory activity on the release of lysosomal contents in vivo.
Catalytic effect of metal ions on the reaction of p-toluenediazonium sulfate and thiocyanate ion was examined with p-tolyl thiocyanate produced using gas-liquid chromatography. The catalytic actiono f bivalent and trivalent iron ions was apparently more effective than that of univalent copper. From these reactions, double complexes of p-toluenediazonium ion with metal thiocyanate of general formula [chemical formula] were isolated. These substances rapidly decomposed when heated above their mp, yielding p-tolyl thiocyanate, which is the same compound obtained by the reaction of the solution of diazonium salts with metal thiocyanates. This is a strong evidence that these double complexes were actually formed in the Sandmeyer reaction.
A fluorometric method for titration of chloride based on Schales and Schales's mercurimetry is described. Anisidine Blue (tetrasodium o-dianisidine-N, N, N', N'-tetraacetate) is used as a fluorescent indicator. The blue fluorescence of the indicator is developed in the region above pH 2.5, and quenched with Hg2+ completely in the pH range of 3 to 4. Titration mixture is composed of 100μl of serum, 1000μl of Macllvaine buffer solution (pH 4), and 500μl of methanol solution of Anisidine Blue (1mg/ml). Titration is carried out under ultraviolet ray, with 0.02N Hg(NO3)2 easily until blue fluorescence is quenched. This method makes possible the direct titration of chloride in clinical materials such as icteric, hemolytic, and lipemic serum.
Phenolic cyclization of 3-hydroxyphenethylamine (XII), 1-(3-hydroxyphenyl)-2-aminoethanol (XIII), 2-(3-hydroxyphenyl) cyclohexylamine (XIV), and 2-(3-hydroxyphenyl) cyclohexanol (XV) with several ketocarboxylic acids gave 1-carboxy-1, 2, 3, 4-tetrahydroisoquinoline derivatives (I-IV), 6-carboxy-1, 2, 3, 4, 4a, 5, 6, 10b-octahydrophenanthridine derivatives (V-VIII), and 6-carboxydibenzo[b, d]pyran derivatives (IX-XI), respectively, which were expected to show an anti-inflammatory activity. In these compounds 1-benzyl-1-carboxy-1, 2, 3, 4-tetrahydro-6-hydroxyisoquinoline (III) and 1-carboxy-1, 2, 3, 4-tetrahydro-6-hydroxy-1-methylisoquinoline (I) were found to have almost the same potent anti-inflammatory activity as phenylbutazone in the initial screening of carrageenin-induced paw edema.
A method for the determination of glycyrrhizin in liquorice roots and its preparation was devised by the use of a high-speed liquid chromatography. Separation can be achieved within 12 min employing a 1-m column packed with Permaphase AAX pellicular anion exchanger, using gradient from H2O to 0.05M NaClO4 solution as an eluant in a Du Pont LC 830 liquid chromatograph. Accuracy in this method was found to be less than ±1.5%, with the relation Y=0.856X-0.538, and a relative coefficient of 0.999.
A series of N-decanoyl methyl esters of α- and γ-glutamyl oligopeptides including the isomer pairs of ten dipeptides, three tripeptides, and one tetrapeptide, in most of which glutamic acid was at the N-terminal, were prepared for use in a study of the mass spectrometric differentiation of the flutamyl peptide isomers. Z-Glutamyl γ- and α-methyl esters were condensed with amino acid or peptide methyl esters by the mixed anhydride, active ester, or dicyclohexylcarbodiimide method to give Z-α- and γ-glutamyl di-to tetrapeptides (1a-1 and 2a-1), respectively, in reasonable yields. These intermediate peptides were then decarbobenzoxylated by catalytic hydrogenation, followed by coupling with decanoic acid by the mixed anhydrode or active ester method to yield the corresponding N-decanoyl-α- or -γ-glutamyl peptide methyl esters (3a-1 or 4a-1). With essentially the same procedure as above, the isomer pairs of glutaminyl dipeptide and glutamyl tripeptide derivatives (3m-1 and 4m-1) were also prepared.
Several aliphatic alcohold such as methanol (Ia), ethanol (Ib), propanol (Ic), butanol (Id), amyl alcohol (Ie), benzyl alcohol (If), isopropyl alcohol (Ig), cyclohexanol (Ih), t-butanol (Ii), and t-amyl alcohol (Ij) were allowed to react with bis(chloromethyl) ether using sodium hydroxide as a base in dimethyl sulfoxide as a solvent, in a noncatalytic heterogeneous reaction, while the concentrations of the alcohols (Ia-j) were maintained low by using an apparatus and procedure devised by the present authors. The corresponding bis(alkoxymethyl) ethers were obtained in a comparatively good yeild with high purity in a short period.
The methanol extract of the leaves of Cerbera manghas L. was treated and from the ethyl acetate fraction, succinic acid, nicotiflorin, and rutin, and from the aqueous layer L-(+)-bornesitol were isolated and identified respectively with authentic samples.