Pantlitschko and others reported that thioxolone (I) is decomposed in alkaline solution to form 2-mercaptoresorcinol (II) and it may be assumed that II thereby formed would easily be oxidized to 2, 2′-dithiodiresorcinol (III). Alkaline decomposition of I was examined by estimation of the intermediate product by iodometry and examination of the polarographic behavior of III to determine the amount of III formed from I. Formation of II is observed when I is left in a solution of over pH 8, the amount increasing with higher pH and becoming maximum at around pH 12. Oxidation of II to III does not occur in a solution of pH 2-3 for 100 minutes but becomes rapid as the solution becomes alkaline from around pH 7, and is the most rapid at around pH 12. Determination of III by polarography revealed that its formation occurs when I is left in a solution of over pH 8 and the amount seems to increase in proportion to the length of time and concentration. III shows a reduction wave and the limiting current is a diffusion current-controlled, n=2.
Reaction between glucuronolactone and glucuronic acid was examined. 1) There is an equilibrium between glucuronolactone and glucuronic acid. 2) This reaction occurs in hydrochloric acid solution by pseudo-first order reaction and is found to be first order with respect to both hydrogen ion and-the lactone or the acid. 3) The thermochemical equation between these lactone and acid can be shown by: C6H8O6+H2O⇔C6H10O7+4.7 kcal.
Hydrolysis of gucuronamide in acid solution was examined. Glucuronamide was hydrolyzed to glucuronic acid, which underwent dehydration and reached equilibrium with glucuronic acid lactone. These reactions have been shown as the consecutive reversible reaction. Hydrolysis reaction of the amide was found to be first-order with respect to both the amide and the hydrogen ion.
Derivatives of 1-phenazinol having a substituent in 9-position, i.e. 1, 9-phenazinediol (II), 9-methyl-1-phenazinol (III), 9-chloro-1-phenazinol (IV), and 9-hydroxy-1-phenazine-carboxylic acid (V), were synthesized and the effect of the 9-substituent on chelate formation was examined by the application of copper and nickel, as the bivalent metals with tendency to take the planar configuration, and of zinc and mercury, which tend to take the tetrahedral configuration. Of the derivatives used, III, IV, and V are new compounds, and III and V were obtained by demethylation of the methylated compounds prepared earlier and further oxidized with chromium trioxide. IV was obtained by demethylation of the methylated compound prepared by Yoshioka′s method. Formation of a chelate compound was judged by the measurement of absorption spectrum in the visible range and its composition was deduced from the molar ratio method. It was thereby found that chlorine and methyl in the 9-position distinctly affected chelate formation with copper and nickel which take the planar configuration and chelate formation was not observed except in the case of copper with the chlorine-substituted derivative. The carboxyl group takes part in chelate formation as the functional group and forms a stable chelate with each of the metals in 1:1 composition. Structure of this chelate compound was examined from its infrared absorption spectrum.
Determination of dulcin was attempted by the application of the diacetyl monoxime method used for the determination of urea. To 1ml. of the aqueous solution of dulcin (20-120γ/ml.), 1ml. of 1% aqueous acetic acid solution of diacetyl monoxide and 1.4ml. of conc. hydrochloric acid are added, heated at 100° for 40 minutes, protected from light, and measurement of ultraviolet absorption of the solution at 500mμ makes it possible to determine the quantity of dulcin. The compound is extremely labile to light and the method is not practicable. Therefore, decomposition of urea with sodium nitrite was attempted. To 1ml. of the dulcin solution in water, 0.6ml. of N hydrochloric acid was added, chilled in ice water, 1ml. of 2 % sodium nitrite solution was added, and allowed to stand for about 5 minutes. Dropwise addition of 1ml. of N sodium hydroxide solution containing 2% β-naphthol produces a reddish orange precipitate which dissolved on addition of 3ml. of ethanol. This clear solution has an absorption maximum at 500mμ and the absorption was found to follow the Beer's rule within the range of 1-150γ/ml. of dulcin concentration, making it possible to use this for its determination.
Ethyl 6, 7-dimethoxy-3, 4-dihydro-1-isoquinolinecarboxylate (I) and its reduction product, tetrahydroisoquinoline (III), from (±)-calycotomine (IV) by reduction of their ethoxy-carbonyl group by treatment with sodium borohydride. N-Methylation of IV gives (±)-N-methylcalycotomine (V), which is also obtained by the reduction of the methiodide of I with sodium borohydride and then with lithium aluminum hydride. Of the acyl derivatives (VI) of V, o-methoxybenzoyl compound (VIc) has twice the antitussive action of narcotise. The amide compounds (VIIa-c) were obtained by the condensation of I and various amines.
In order to examine their pharmacological action, acyl derivatives of 1-methyl-6, 7-methylenedioxy- and -6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline-3-methanol (Va and b) and 1, 2-dimethyl-6, 7-methylenedioxy-1, 2, 3, 4-tetrahydroisoquinoline-3-methanol (XI) were synthesized, Various methods were examined for the preparation of V and X, and good results were obtained by the route of I→II→III→IV→V and I→II→III→IV→IX→X.
An extract of Korean corydalis was processed as shown in Chart 1, and protopine, α-allocryptopine, berberine (chloride and iodide), palmitic acid, and stigmasterol were isolated and identified. Two kinds of phenolic bases (picrate, m. p. 172-173°(decomp.), C26H28O11N4, and of m. p. 275-277°(decomp.) (in vacuo)), yellow needles, m. p. 290-290.5°, C20H14O6, and colorless microneedles, m. p. above 300°, assumed to be a glycoside (acetate, m. p. 156-158°), were isolated. A liquid fatty acid was derived to its methyl ester, and the presence of oleic, linoleic, and linolenic acids was confirmed by gas chromatography.
Effect of several monoguanidino derivatives was tested on the electrically elicited contraction of frog sciatic nerve-sartorius muscle preparation and following results were obtained: β-Guanidinoethyl phosphate (II) is guanidine-like compound and promoted the muscle contraction at 10-2-10-3M and depressed it at 10-1M. Creatine (III) and arginine (IV) did not affect the contraction. Benzyl-(VI), phenethyl-(VII), [2-(N-methyl-N-phenylamino)-ethyl]-(VIII), [2-N, N-diphenylamino)ethyl]-(IX), [2-(hexahydro-1-azepinyl)ethyl]-(X), and [2-(octahydro-1-azocinyl)ethyl]-guanidine (guanethidine) (XI) showed neuromuscular block as reported on 1, 1′-decamethylenediguanidine (V) previously. Antagonism between these neuromuscular-blocking monoguanidines and potassium chloride, neostigmine, and edrophonium was tested and it was found that the neuromuscular blocking action of these monoguanidines were antagonized by potassium ion but not by anticholinesterases. From these results, it is concluded that these monoguanidines are neither competitive- nor depolarizing-type muscle relaxants. Guanidine and II antagonized against all these neuromuscular blocking monoguanidines, d-tubocurarine chloride, and succinylcholine chloride. The mode of action of II would differ from that of guanidine, since prior to its antagonistic action, II showed a transient potentiation of neuromuscular blocking action of compounds mentioned above, while guanidine showed only an antagonistic action.
Activity of copper-chromium oxide catalyst was compared by the measurement of the rate of hydrogenation of whale oil at 180° and atmospheric pressure. When the catalyst is reduced at 160° for 1.5 hours and further at 180° for 0.5 hours, the activity of the catalyst for dry method is inferior to the wet method in Tsubaki oil. The latter catalyst has activity comparable to unreduced catalyst activated during hydrogenation at 180°. The fact that this hydrogenation reaction is of zero order with respect to the initial concentration of whale oil under this experimental condition was re-examined with reduced copper-chromium oxide catalyst. Tsubaki oil, whose chief component is oleic acid and which is inactive to this catalyst, was used for dilution of whale oil.
It had been found that ordinary-pressure hydrogenation of whale oil with copperchromium oxide catalyst is of zero order with respect to the initial concentration of the substrate. However, hydrogen absorption frequently followed an apparent first-order reaction formula with respect to the concentration of the substrate. This fact suggests the formation of a catalyst poison in proportion to the degree of hydrogenation. The present series of experiments has shown that there is no formation of a catalyst poison even when the oil and the catalyst are heated for a fairly long time at 180° in vacuum or in carbon dioxide atmosphere prior to hydrogenation. This fact supports the above assumption that there is a close relationship between the formation of a catalyst poison and hydrogenation. A detailed examination was then made on the poisoning of the catalyst during hydrogenation of whale oil with copper-chromium oxide catalyst at 180° in ordinary-pressure of hydrogen. The rate decreasing curve followed an apparent first-order reaction formula but seemed to be composed of many straight lines. In fact, the reaction rate maintains a constant value for a certain range of hydrogenation but drops suddenly, and these phenomena are repeated successively. These experimental facts indicate that there is a discontinuous adsorption of the poison on the active site of the catalyst, or that there is a hysteresis in the adsorption of catalyst poison or desorption of the substrate. A similar phenomenon had been observed in the ordinary-pressure hydrogenation of ethylene with the same catalyst and a hysteresis in desorption of ethylene and hydrogen was described earlier.
Methods were examined for the syntheses of 1-acetylpiperazine (IV) and 1-[(2-methoxy-4-propylphenoxy)acetyl]piperazine hydrobromide (X), the intermediate for obataining asymmetric 1, 4-disubstituted piperazine derivatives which are interesting as antipyreticanalgesic. Compounds XI to XIII were obtained. Over 20 kinds of 1, 4-bis(aryloxyacetyl)piperazine derivatives were obtained by the reaction of 1, 4-bis(haloacetyl)piperazine and phenols, as shown in Table II.
The neutral fraction of the ether extract of the dried root of Panax ginseng C. A. MEYER was submitted to low-pressure distillation and separated into low- and high-boiling fractions. The low-boiling fraction was purified through gas and alumina-column chromatographies and the presence of β-elemene was proved. The high-boiling fraction was submitted to the silica-column chromatography and a new component, panaxynol, was isolated. Its infrared absorption spectrum revealed the presence of a double and triple bonds, and a hydroxyl group. The saturated alcohol obtained by the catalytic reduction of panaxynol was oxidized with chromic acid and the saturated ketone thereby obtained was submitted to the Schmidt decomposition, from which this ketone compound was assumed to be 3-heptadecanone and that the saturated alcohol would be 3-heptadecanol. 3-Heptadecanone was synthesized by the route shown in Chart 2. It was thereby revealed that the basic structure of panaxynol would be a straight-chain unsaturated alcohol with 17 carbon atoms and that the hydroxyl is located at 3-position.
Partial and other reduction of panaxynol, obtained from the ether extract of the dried root of Panax ginseng, revealed the presence of one triple bond and three double bonds in this alcohol. Ozone oxidation of panaxynol afforded octanal and formaldehyde, and permanganate oxidation panaxynol afforded octanoic acid. Consequently, it was assumed that partial structure of CH3-(CH2)6-CH=CH- and -CH=CH2 would be present in panaxynol. Oxidation with active manganese dioxide gave a conjugated unsaturated ketone, thought to have the partial structure of CH2=CH-CO-C≡C-, from comparative examination fo its infrared absorption spectrum with that of panaxynol. From these evidences and from the examination of nuclear magnetic resonance and ultraviolet spectra of panaxynol, the structure of 1, 7, 9-heptadecatrien-4-yn-3-ol is proposed for panaxynol.
Separatory detection of thioctic acid and its related compounds by gas chromatography was examined. The mixtures of thioctic acid and thioctamide, and of thioctic acid and dihydrothioctic acid were completely separated by direct injection without no thermal changes, using the column packing of 15% poly (diethylene glycol succinate) on Chromosorb W at 220-230° and a hydrogen flame ionization detector. The simplicity and high specificity of the method will make it applicable to the quantitative determination of these compounds.
Examinations were made on the nonphenolic tertiary bases in the rhizome of Corydalis ambigua CHAM. et SCHLECHT. var. amurensis MAXIM. (Japanese name, Ezoengosaku) and base (VI), C20H21O4N, m.p. 171-172°, (possibly sinactine), and dl-tetrahydropalmatine were isolated. Presence of canadine was suggested from the result of thin-layer chromatography. Base (I), isolated earlier, was identified by mixed fusion with d-corybulbin, kindly supplied by Dr. Manske. Examinations were also made on quaternary bases in this rhizome and dehydrocorybulbine, dehydrobase (II), dehydrocorydaline, and palmatine were isolated as the protoberberine-type bases. All the alkaloids found in the rhizome of Corydalis ambigua CHAM. et SCHLECHT. var. amurensis MAXIM, are listed in Table I.
Fifteen kinds of o-aminophenol derivatives, including 2-(2, 4-dihydroxy-6-methyl- and-5-ethyl-benzylideneamino) phenol and sodium (o-hydroxyanilino) methanesulfonate, were synthesized. Of the compounds synthesized, sodium (o-hydroxyanilino) methanesulfonate is easily soluble in water and showed antibacterial action, at 6.25γ/ml., against human-type sensitive H37Rv-S strain tubercle bacilli and on H37Rv-S strain resistant to isonicotinoyl hydrazide, streptomycin, and PAS, while o-aminophenol is effective at 1.25γ/ml. concentration. However, the toxicity of this sodium salt is 1/10 that of o-aminophenol and a fairly good clinical result was observed in combined use with kanamycin and cycloserine.
Various kinds of O-acylthiamine chloride hydrochloride (I) can be obtained by the reaction of thiamine monochloride (III) and various aliphatic or aromatic acid chloride, directly or in pyridine, or of thiamine chloride hydrochloride (II) and lower aliphatic acid, directly or in the presence of acid anhydride.
1, 3, 5-Trinitrobenzene was easy to use and sensitive enough to detect cardiac glycosides on paper or thinlayer chromatograms. Trinitrobenzene solution (0.1% in a mixture of dimethylformamide and water) and sodium carbonate solution (5% in water) are successively sprayed on the developed chromatogram and this is heated at 90-100° for 4-5 minutes. When cooled sodium dihydrogenphosphate solution (5% in water) is sprayed by which cardiac glycoside is revealed as an orange-red spot on an almost colorless background. The limit of detection of some cardiac glycosides is tabulated in Tables I and II.