In order to determine the amount of sodium anilino-N-glucopyranosiduronate in aqueous solution and in urine, separatory procedure by anion exchange resin was carried out. By the determination of amino-nitrogen in the part eluted by N hydrochloric acid by the modified Van Slyke method, various conditions necessary for determination of sodium anilino-N-glucopyranosiduronate were examined.
Urine from diseased and normal children was treated with anion exchange resin, as described in Part II of this series, and the part eluted by N hydrochloric acid was submitted to paper chromatography and determination of amino-nitrogen to follow quantitative relationship with glucuronic acid. From the urine of diseased children, paper chromatographic spot positive to Tsuda, Ehrlich, and ninhydrin reagents was detected and molar ratio of amino-nitrogen to glucuronic acid was greater than that in normal urine, the values being 35.7-108.4 in the diseased urine and 9.6-12.3 in normal urine. The value tended to approach the normal value as the disease improved.
It was assumed that the fluidity of a semisolid coming out of a rotary wet granulator was dependent on the flocculation of particles, surface tension of a binder solution, and ease of wetting, and rheological properties of a semisolid were measured by a strain gauge. State of flocculation was estimated by measurement of sedimentation volume and ease of wetting was measured by Washburn's formula (1). It was thereby revealed that the two following factors were chiefly responsible for the fluidity of a semisolid. a) When limited to the diameter of particles, fluidity is generally better in particles with larger diameter than those of smaller diameter, both in binder solutions which flocculate and which do not flocculate the particles. b) When limited to binder solutions, fluidity increases with increasing adhesion tension of a binder which flocculates the particles. In a binder solution which does not flocculate the particles, fluidity is affected by the velocity of wetting and fluidity increases with slower velocity of wetting.
Application of cationoid reagents to p-trimethylsilyl-N, N-dimethylaniline (III), same as that on p-trimethylsilylphenol (I) and p-trimethylsilylaniline (II), was examined. Application of bromine to (III) afforded p-bromo-N, N-dimethylaniline, that of nitrous acid gave p-nitrouo-N, N-dimethylaniline, and nitration of (III) with acetyl nitrate gave p-nitro-N, N-dlmethylanlllne. Application of p-nitrobenzenediazonium chloride or benzenediazonium chloride to (III) was found to produce 4-dimethylarnino-4′-nitro-azobenzene in the case of the former, but (III) was recovered with the latter reagent. These experiments proved that application of cationoid reagents to (III) tended to cause substitution of ring-carbon bonded to the trimethylsilyl group, same as in (I) and (II).
Catalytic reduction of a mixture of 3- and 4-trimethylsilyl-1-nitrobenzene over palladium-carbon catalyst, hydrolysis with dil. hydrochloric acid, and fractional distillation of the hydrolysate afford 3-trimethylsilylaniline in a good yield. Bromination of 3-trimethylsilylacetanilide (II) gives the 4-bromo compound (III), whose further bromination affords 3, 4-dibromoacetanilide. Nitration of (II) affords 2-nitro-5-trimethylsilylacetanilide (IV), whose catalytic reduction over palladium-carbon gives 2-amino-5-trimethylsilylacetanilide (V). (V) is easily hydrolyzed by dil. hydrochloric acid to form 2-methylbenzimidazole. Bromination of 4-trimethylsilyl-1, 2-phenylenediamine diacetate gives 4-bromo compound. These experiments have revealed that the introduction of o, p-orienting groups in the position ortho or para to the acetamide group in (II) weakens the bond between silicon and aromatic ring due to over-lapping of the +T effect of the group introduced and +I effect of the trimethylsilyl group, and that the second substitution occurs at the ring-carbon to which the trimethylsilyl group is bonded.
In order to examine the direct resolution of dl-threo-1-p-nitrophenyl-2-amino-1, 3-propanediol reported by Amiard and others, its racemic structure was examined by thermal analysis and infrared absorption spectrum, and it was revealed that the racemic compound is a racemic conglomerate. Solubility of this compound in various solvents was measured and, from its solubility in water, heat of differential solubility was calculated. From the theory of Meyerhoffer, the racemic compound of this substance was proved to be a racemic conglomerate.
Zone electrophoresis of cobra venom was carried out with starch as a carrier and under conditions of pH 7.5 (acetate buffer, μ=0.15), 470V, 24mA, and at 2° (length of starch block, 55cm.). Formosan cobra venom was separated into three protein fractions. The two portions closest to the anode were found to contain lecithinase-A, glycerophosphatase, phosphodiesterase, strongly toxic component (neurotoxin), two kinds of phosphomonoesterase, and at least two kinds of 5′-nucleotidase. The peak of neurotoxin did not agree with that of lecithinase-A and other enzyme-active peaks, and therefore there is no connection between these enzymatic activity and toxicity. It may be concluded that lethal action of Formosan cobra venom is solely due to this neurotoxin because recovery rate of toxicity of this fraction reached ca. 92%. The other one portion which transits most rapidly to the cathode side did not show the enzyme activity described above.
Formosan Habu venom was fractionated by zone electrophoresis using starch as a carrier and examinations were made on enzyme activity and biological activity of each fraction. Hemorrhagic activity was not in proportion to the protease activity as measured with casein as the substrate and their peaks were not in agreement. It follows, therefore, that the component with strong hemorrhagic activity obtained from Formosan Habu venom has no protease activity or even if this activity is present, it must be extremely weak. The venom was also found to contain at least two kinds each of lecithinase and proteolytic enzyme.
A new substance of m.p. 197-197.5°, C15H16O5(I), considered to be 2-methylchrornone derivative, was obtained from the root of Angelica japonica A. GRAY. Besides this substance, the root afforded, as a coumarin compound, isobyak-angelicolic acid (II), m.p. 210-211°, C17H18O7, byak-angelicin (IV), m.p. 125.5-126°, C17H18O7, psoralen (V), m.p. 163-163.5°, C11H6O3, isopimpinellin (VI), m.p. 148-149°, C13H10O5, and osthol (VII), m.p. 83-83.5°, C15H16O3. Further, a carboxylic acid (III), m.p. 77-77.5°, considered to be lignoceric acid, and a steroid of m.p. 163.5-164° were also obtained. Scopoletin and umbelliferone were detected by paper chromatography and paper electrophoresis.
Some time ago, Kariyone and Sawada found a flavonoid from the leaves of Chamaecyparis obtusa ENDLICHER and named it hinokiflavone, giving a formula of C30H12O4(OH)6. In spite of the fact that this composition agrees with that of demethylated compound of bis-flavonoid, ginkgetin and sciadopitysin, it was found to be not identical and these workers assumed that this substance must be a bis-flavonoid with linkage positions different from that of known bis-flavonoids. It was established by the present series of work that the formula of hinokiflavone is C30H15O5(OH)5. Decomposition of hinokiflavone with 25% potassium hydroxide solution afforded p-hydroxyacetophenone, a flavonoid of C23H13O4(OH)3, phloroglucinol, and a phenolic ketone of C14H12O5.
The phenolic ketone (Substance X), C14H12O5, obtained by decomposition of hinoki-flavone with 25% potassium hydroxide, was established as 2, 4, 6-trihydroxy-4′-acetyl-diphenyl ether. The same decomposition of ketoflavone was found to produce Substance X and p-hydroxyacetophenone, and from this fact and from its composition, ketoflavone was revealed to be 8- or 6-(p-acetylphenoxy)-5, 7, 4′-trihydroxyflavone.
Decomposition of hinokiflavone pentamethyl ether with ethanolic potassium hydroxide produces anisic acid, p-methoxyacetophenone, 2-hydroxy-4, 6-dimethoxyacetophenone, a phenolic acid (Substance Y) of formula C17H16O7, and a phenolic diketone (Substance Z) of formula C18H18O6. Substances Y and Z were determined to have the respective structure of 2-hydroxy-3-acetyl-4, 6-dimethoxy-4′-carboxydiphenyl ether and 2-hydroxy-3, 4′-diacetyl-4, 6-dimethoxydiphenyl ether. All these substances, except 2-hydroxy-4, 6-dimethoxyacetophenone, originate from the ketoflavone structure, so that hinokiflavone should have one phloroglucinol system besides a ketoflavone. From these facts, it was concluded that hinokiflavone has a diphenyl ether-type bisflavonoid structure in which two moles of aplgenin are bonded in ether linkage at their 4′- and 8-position.
Decomposition of hinokiflavone pentamethyl ether, C30H13O5(OCH3)5, with methanolic barium hydroxide solution is not a complicated reaction, unlike the case of ethanolic potassium hydroxide, and three substances, anisic acid, Substance Y (C17H16O7), and 2-hydroxy-4, 6-dimethoxyacetophenone, are obtained in good yield. Such a fact proves that the structure of hinokiflavone proposed in the preceding report is reliable. A mild decomposition of hinokiflavone with ethanolic potassium hydroxide afforded a β-diketone corresponding to ketoflavone and its cycllzation gave a carboxy-flavone.
Pale yellowish white microneedles, m. p. 238-239°, were obtained in 0.1% yield from the leaves of Thalictrum Thunbergii DC. This substance colors blood red to ferric chloride, orange-red to magnesium and hydrochloric acid, and has optical rotation of [α]D19-116.19°. Its hydrolysis with 10% sulfuric acid afforded one mole each of apigenin and galactose. This was named thalictiin. Complete methylation of thalictiin followed by hydrolysis gave 5, 4′-dimethoxy-7-hydroxyflavone and the position of sugar bonding was determined as 7 and thalictiin is therefore shown to be apigenin 7-galactoside.
Velocity of acylation and deacylation reactions in 2, 2-dimethyl-5-amino-6-(p-nitrophenyl)-1, 3-dioxane, related to chloramphenicol, was compared in threo and erythro systems. It was thereby found that the reaction is more facile in the threo compound in which the amino group is in axial position, than in the erythro compound in which the amino is equatorial. However, a reverse result had been obtained in cyclohexane derivatives. This is probably due to the fact that, in cyclohexane derivatives, the axial amino group remains somewhat inert to the reaction by the 1, 3-diaxial interaction, while such interaction cannot be considered in 1, 3-dioxane derivatives where the two hetero-atoms, oxygen, occupy the 1, 3-position, and the reaction is more inhibited in the erythro compound in which NH2-H interaction is greater.
Application of benzaldehyde to 1-(p-nitrophenyl)-2-benzylideneamino-1, 3-propanediol (III) results in cyclization to form 2, 8-diphenyl-6-(p-nitrophenyl)-1-aza-3, 7-dioxabicyclo[3.3.0]octane (I). Comparison of the velocity of cyclization of (III) between the threo and erythro systems showed that the threo compound was more easily cyclized than the erythro compound. Analysis of this fact from the conformation of these two isomers suggested that in the transition state of this reaction, two large groups in the erythro compound are in eclipse, producing a large steric repulsion, and the reaction velocity becomes slower. Application of methyl dichloroacetate to (III) afforded chloramphenicol and (I), and this reaction was found to occur almost without difference in the threo and erythro systems of (III). This may be affected by an acylation factor but another reason may be the difficulty of separation the products completely after the reaction.
Majority of coumarins exhibit fluorescence. Fluorescence spectra of about 25 kinds of coumarins were measured, the fluorescent color was represented by their maximum wave length, and examinations were made on the relationship between fluorescence spectrum and chemical structure. It was thereby found that the fluorescence of coumarins originated in the benzene ring and α, β-unsaturated ketone group and that the fluorescence spectra showed great variation when a side chain was present, especially that with a polar group. The fluorescence was also affected to a certain extent by the number and position of the side chain.
Fluorescence spectra of furo-coumarins were measured and relationship between fluorescence and chemical structure was examined. Fluorescence of furocoumarins is generally in a longer wave-length region than that of coumarins, is yellowish green in color, and the fluorescence was found to change according to the number, position, and kind of a side chain present. In general, the fluorescence of furocoumarins is stable and the amount of total fluorescence was measured in consideration of application to fluorescence analysis. It was found that the fluorescence is generally weaker than that of coumarins but there seemed to be such a possibility.
Since majority of coumarin derivatives exhibit fluorescence, a series of fluorescence analysis of these compounds was planned. Fluorescence ability and stability of fluorescence were examined in 21 kinds of coumarins and 9 kinds of furocoumarins, and it was found that fluorescence analysis is possible with most of them. Selective fluorescence filter suitable for each of these compounds was determined and the concentration range at which linear relationship was established between the sample concentration and relative fluorescence intensity, i.e. concentration range in which fluorescence determination was possible, was established.
3, 4-Dihydroxyacetophenone was obtained from the leaves of Picea pungens ENGLM. var. glauca BEISS and its distribution in the leaves of plants of Picea genus was established. A new glycoside formed by bonding of β-D-glucoside to this substance was confirmed and the bonding position was established as the hydroxyl at 3-position. The structure of 3, 4-dihydroxyacetophenone 3-β-D-glucoside was given for this substance which was named pungenoside.
2, 3-Disubstituted 4-picolines (III) were prepared from 1, 1, 3-triethoxybutane (I), ammonia, and ketones (II) by catalytic vapor-phase reaction with cadmium phosphate-acid clay catalyst. By this reaction, the use of acetone afforded 2, 4-lutidine (IV) (yield, 42%), use of methyl ethyl ketone gave 2, 3, 4-collidine (V) (yield, 35%), that of acetophenone gave 2-phenyl-4-picoline (VI) (yield, 31%), that of propiophenone gave 2-phenyl-3, 4-lutidine (VII) (yield, 26%), and that of phenylacetone afforded 3-phenyl-2, 4-lutidine (VIII) (yield, 33%) and a by-product, 2-benzyl-4-picoline (yield, 7%). 4-Methyl-5, 6, 7, 8-tetrahydroquinoline (X) was obtained in 34% yield from (I), ammonia, and cyclohexanone. When (I) and ammonia alone are passed over cadmium phosphate catalyst at 400°, the base obtained was 4-methyl-5-ethylpyridine (XI) as the main product, with a small amount of 2-methyl-5-ethylpyridine (XII) as a by-product. Of the bases obtained, (VII) and (VIII) are new compounds and their structures were determined by permanganate oxidation, thermal decomposition, and ultraviolet spectral measurement.
In continuation of the preceding work, thiocyanation was carried out by the Kaufmann method on 2-formamido-, 2-formamido-4-methyl-, 2-ethoxycarbonylamino-, and 2-ethoxycarbonylamino-4-methyl-thiazoles, and four kinds of corresponding 5-thiocyano derivatives were prepared. Of these derivatives, 2-formamido-5-thiocyanothiazole had the best solubility in solvents and seemed hopeful as the antifungal agent.
Two kinds of biscoclaurine-type bases were prepared by the Ullmann reaction of two benzyl-tetrahydroisoquinoline type bases. One of the starting materials, dl-1-(3-bromobenzyl)-2-methyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline (VII), was prepared by the route illustrated in Chart 1 and the Ullmann condensation of (VII) with dl-1-(3-hydroxybenzyl)-2-methyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline (IX) gave dl-3, 3′-bis (2-methyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydro-1-isoquinolylmethyl) diphefyl ether (XI). The same Ullmann condensation of (IX) and dl-1-(2-bromobenzyl)-2-methyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline (XII) afforded dl-2, 3′-bis (2-methyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydro-1-isoquinolylmethyl) diphenyl ether (XIII).
Sulfonation of dibenzo-p-dioxin (I) with conc. sulfuric acid or with chlorosulfonic acid in carbon tetrachloride affords a dlsulfonic acid in either case. The acid was derived to 2, 7-dibromodibenzo-p-dioxin (VII) by the route shown in Chart 1 and the position at which ring-substitution occurs by sulfonation was proved to be 2 and 7. Further, sulfonation of 2, 7-dimethyldibenzo-p-dioxin (VIII) also gives a disulfonic acid which was derived to 2, 7-dimethyl-3, 8-dibromodibenzo-p-dioxin (XV) by the route shown in Chart 1, and ring substitution by this sulfonation was proved to occur at 3- and 8-positions.
1) Yield of crop of the second-year growth of Artemisia kurramensis QAZ., sown in the autumn, was comparable to that sown in the spring (Table I). This is in agreement with the result reported in Part III of this series and shows the possibility of cultivation of this plant by autumn sowing. 2) The season at which the santonin content reaches the maximum was in the early part of August, both in the first- and second-year growths (Tables I and III). It has been proved by tests during the past three years that there is no essential difference between the first- and second-year growths as to the period at which the santonin content reaches the maximum in the same year. 3) It was found that the rate of dead stocks after harvest was smaller when shoots are harvested in parts rather than as a whole. In some cases, partial harvesting raised the yield of crop to 70-99% of that from total harvesting of shoots (Table IV). This fact suggests the possibility of such a process for actual harvesting. 4) It is possible to carry out transplantation in the autumn for harvesting the second-year growth. This is to sow seeds in the spring, as early as possible, transplanting the seedlings during May in a provisional bed, and to plant them in the field during the autumn. By this means, a larger yield of crop was obtained although there was no significant difference in the santonin content from the plants sown in the autumn and transplanted in the field during the spring (Tables V to VIII).
1) F1 plants, obtained by crossing two plants of Artemisia kurramensis QAZ. with high santonin-content, showed higher content of santonin both in the first- and second-year growths than the control (Tables I, II, and IV). This fact has confirmed the effect of breeding by line separation 2) Santonin content was determined in F1 plants during the first year (1956) and second year (1957) by comparing individual plants and a significant positive correlation was found between the first- and second-year growths. Considering the results reported in Part VII of this series, it is concluded that the santonin content in Artemisia kurramensis QAZ. is hereditary. 3) Family selection of this plant from two individuals with high santonin content and good growths failed to afford F2 seeds. This was considered to be due to the harm of sib cross. 4) In tests during 1956, two individuals with β-santonin were found from 33 individuals of the fourth-year growth. This indicates the presence of a strain containing β-santonin and removal of such individual is the most essentials point in the cultivation of this plant. 5) When the seeds which are usually collected in January are left to stand at normal temperature and humidity, the seeds lose the power of germination by autumn of the same year. When kept in a desiccator with ad rying agent, life of the seeds remains for about two years (Table V).
1) In cultivation of the second-year growth of Artemisia kurramensis QAZ. by transplanting in the spring, those sown in the autumn should be planted more closely (around 80×15cm.) than those sown in the spring. By this means, yield of crop from autumn sowing becomes comparable to those sown in the spring (Table I). It has been confirmed by past studies that there is no essential difference between the spring and autumn sowing in the period at which the santonin content reaches the maximum (Tables I and TV, and IV in Part IX. 2) It seems more advantageous to transplant the first-year growth in the field with the distance of 60-66cm. between rows and 15cm. between stocks, and to harvest the plants during the middle of August to early part of September, i.e. 0.5 to 1 month after the santonin content reaches the maximum (Table II). 3) It is possible to cultivate the first-year growth of Artemisia kurramensis between rows of barley, before or after its harvest, and this was found to give medium yield of crop (Table IX). 4) In the cultivation of second-year growth by transplantation in the autumn, higher rate of living after the winter is obtained the earlier the transplantation in the field, and yield of crop was larger (Tables III and IV). The period of transplantation does not affect santonin content but significantly affects the yield of crop. This indicates that the transplantation should be made during November at the latest (Tables V to VIII). 5) Following conclusions were drawn as a result of cultivation tests carried out during the nine years from 1050 to 1958: (a) In general, santonin content of Artemisia kurramensis reaches the maximum at the same period (during July, especially from middle to the end of July) in the same year, irrespectively of the age of plants, although a slight retardation (ca 1.5 weeks) may sometimes occur due to the presence or absence of, or period of, transplantation in the field during the spring. (b) The period at which the yield of crop (especially the air-dried useful crop) reaches the maximum generally differs according to age of plants and the manner of cultivation. In first-year growth, this reaches the maximum 1 to 1.5 months after the santonin-content reaches the maximum, i.e. during the early to middle part of September. On the other hand, that of the second-year growth reaches the maximum 0.5 to 1 month after the santonin-content reaches the maximum, i.e. during the early to middle part of August in the plants transplanted in the field during the autumn, and during the middle to late part of August in those transplanted in the field during the spring. (c) In general, the period at which the yield of santonin per unit area reaches the maximum does not necessarily agree with the period at which santonin content of the individual reaches the maximum, and the period also differs according to age of plants. In the first-year growth, this is affected by the amount of air-dried useful crop and reaches the maximum 1 to 1.5 months after the santonin content reaches the maximum, during the early to middle part of September. In the second-year growth, this is related to the santonin content of individual plants, irrespective of the manner of cultivation. This period either agrees entirely with that of the highest content of santonin or is only about 1.5 weeks later, reaching the maximum during the middle of July to the early part of August.
Hydnocarpic and chaulmoogric acids present as the main effective principles in various kinds of hydnocarpus oil were prepared. Hydnocarpic acid, d-11-(2-cyclopentenyl) undecanoic acid, was obtained as hydrocarpohydroxamic acid, m. p. 76-77.5°, [α]D22+75°, and chaulmoogric acid, d-13-(2-cyclopentenyl) tridecanoic acid, as chaulmoogrohydroxamic acid, m. p. 83-84.5°, [α]D22+64°. The complex salts formed from these hydroxamic acids by reaction with ferric chloride are the most stable in dehyd. alcohols and the ultraviolet absorption spectra shown in Fig. 1 indicated the formation of four types of complex salts in dehyd. ethanol.
Composition of the complex salt, formed from hydnocarpo- and chaulmoogrohydroxamic acids by reaction with ferric chloride in dehyd. ethanol was obtained from experimental results by application of the Vosburgh-Cooper method, one of the continuous variation methods (Figs. 1 and 2) and those by the molar-ratio method (Figs. 3 and 4, and Tables I and II), and from the ultraviolet absorption spectral data. The salts were found to be present in several kinds of composition (four types were recognized from absorption spectra), as indicated by the molar ratio of the hydroxamic acid to FeCl3⋅6 H2O: 1.0:1.5 and 1.0:1.0 ratios with absorption maximum at 525mμ; 1.5:1.0 ratio with absorption maximum at 505mμ; 2.0:1.0 ratio with absorption maximum at 495mμ; 3.0:1.0 to 6.0:1.0 ratios with absorption maximum at 485mμ. It was found that the Beer's law was established for these complex salts in dehyd. ethanol (Fig. 5).
Rats were given 65ZnCl2 and their internal organs were examined by autoradiography. It was thereby found that 65Zn is deposited in high concentration in the prostate gland. The prostate was taken out, homogenized, and the homogenate was centrifuged by which majority of the radioactive zinc (70%) transited to the water-soluble portion. The water-soluble peptide was submitted to paper chromatography, using butanol-acetic acid-water (4:1:3) as the solvent and a spot appeared at around Rf 0.25 which colored bright red to ninhydrin and pinkish violet to dithizon. By scanning for the radioactive zinc on this chromatogram, the presence of radioactive zinc was detected at Rf 0.25, and the ultraviolet spectrum of this portion indicated absorption maximum at 262mμ. The same result was obtained on administration of 65Zn-histidine to the rat. Paper chromatography of the homogenate of the prostate from ordinary rat hardly gives any spot at around Rf 0.25 which colors red to ninhydrin but the spot colors slightly with dithizon. Ultraviolet spectrum of this portion shows a slight absorption at 260-262mμ. The hydrolyzate of the water-soluble peptide with hydrochloric acid gave one spot on paper chromatogram at Rf 0.27 for zinc-bound amino acid and this spot is that of Zn-histidine with absorption maximum at 262mμ.
Sodium glutamate and histamine hydrochloride were each administered to man and rabbit and the urine, after lyophilization, was submitted to circular paper chromatography, comparing the results with in vitro experiments. It was thereby found that a ring spot coloring both to ninhydrin and anisidine hydrochloride appeared in both cases and indicated that these amines form N-glucuronide in vivo.
Phenanthridine 5-oxide (I) is reduced to phenanthridine (II) by catalytic reduction over Raney nickel or by reaction with phosphorus tribromide. (I) is oxidized with hydrogen peroxide in alkaline medium into 6-hydroxyphenanthridine 5-oxide (IV). (I) produces (V) on reaction with acetic anhydride or with tosyl chloride followed by reaction with potassium carbonate. Reissert reaction of (I) affords, besides (V), 6-cyanophenanthridine (VI) which is also obtained in a good yield by application of dimethyl sulfate to (I) to form the quaternary salt and its reaction with potassium cyanide. (I) can be prepared in a good yield by heating (II) in acetic acid with hydrogen peroxide at 80-85° for 5 hours.
Phenanthridine-6-carboxaldehyde (I) is inert to benzoin condensation using potassium cyanide but the use of 1, 3-dimethylbenzimidazolium hydroxide (IV) results in formation of phenanthridoin (II). By a similar process, quinoline-2-carboxaldehyde (V) forms quinaldoin (VI).
Catalytic reduction at ordinary temperature and pressure, using Urushibara nickel-B in methanol, was carried out on quinoline 1-oxide (I), 4-chloropyridine 1-oxide (II), 4-methoxypyridine 1-oxide (III), and 4-benzyloxypyridine 1-oxide (IV), and they were respectively deoxygenated. In the case of 4-nitropyridine 1-oxide (IX), reduction in methanol chiefly afforded 4, 4′-azopyridine (XI), with a small amount of 4, 4′-azoxypyridine 1, 1′-dioxide (XII) and 4, 4′-hydrazopyridine (XIII). When this reduction is carried out in methanol containing a small amount of acetic acid, 4-aminopyridine (XI) was chiefly produced, besides a small amount of (XI) and (XIII). This is approximately the same as in the use of Raney nickel, except in the case of (IX), but the velocity of the reaction is somewhat slower with Urushibara nickel.
Nitration of benzyl acetate (V) with acetyl nitrate was found to produce o-nitrobenzyl acetate (I) and p-nitrobenzyl acetate (II) in 63:37 ratio, with a total yield of 90%. Hydrolysis of (I) and (II) with hydrochloric acid respectively afforded o-nitrobenzyl alcohol (III) and p-nitrobenzyl alcohol (IV).
In order to examine the chemical properties of quinazoline-4-carbonitrile (I), its Radziszewski reaction and alcoholysis were carried out. (I) was derived to quinazoline-4-carboxamide in a good yield. The hygroscopic crystalline product obtained by introduction of dry hydrogen chloride gas into a solution of (I) in a mixed solvent of dehyd. methanol and chloroform was submitted to treatment with acid and alkali. Acid treatment afforded the corresponding acid amide (II) alone while alkali treatment afforded methyl quinazoline-4-carboxylate (III) as well as (II). (III) was easily derived to quinazoline-4-carbohydrazide by application of 80% hydrazine hydrate. These observations are entirely identical with the result of Radziszewski reaction and alcoholysis of 4-alkoxyquinazoline-2-carbonitrile (A).
Examinations were made on the dialyzable portion of a venom from Formosan Habu (Trimeresurus mucrosquamatus CANTOR). Paper chromatography and paper electrophoresis revealed the presence of 11 kinds of amino acid, spermine, and histamine. Histamine was also detected by development of crude venom by paper electrophoresis and coloration with the diazo reagent.
Systematic fractional treatment was carried out on the alkaloids of Berberis Thunbergii DC. (Japanese name ‘Megi’) and the presence of isotetrandrine was proved as the tertiary, non-phenolic, biscoclaurine-type base, besides the alkaloids found to date. Further, presence of a new water-soluble, quaternary base in extremely minute quantity was proved as a picrate of m. p. 217-223°. This is the first example of a presence of non-phenolic, biscoclaurine-type base in the Berberis genus plants.
Examinations were made on the alkaloids present in Formosan Berberis Kawakamii HAYATA (Japanese name ‘Kuromino-hebinoborazu’) and the presence of berbamine and isotetrandrine was proved as the biscoclaurine-type bases. Water-soluble quaternary bases found in this plant were the protoberberine-type berberine, palmatine, and jatrorrhizine, and the aporphine-type magnoflorine.
Examinations were made on the alkaloids present in Formosan Berberis mingetsensis HAYATA (Japanese name ‘Usuba-hebinoborazu’) and the presence of berbemine and isotetrandrine as the tertiary biscoclaurine-type bases, and oxyberberine as the berberine-type base was proved. Water-soluble, quaternary bases present were the berberine-type berberine, palmatine, and jatrorrhizine, and the aporphine-type magnoflorine.
1) Artemisia caerulescens L. sensu primario (=A. caerulescens L. var. latifolia DC.), obtained from Yugoslavia, was cultivated at Kasukabe during 1957 and 1958. 2) Seasonal variation in the santonin content and yield of crop of the second-year growth of this plant, sown in March, 1957, were followed from June 2, 1958, to September 22, 1958 (Table I). It was thereby found that the yield of crop (on air-dried basis) per 10 ares was the greatest in the one collected on July 11, being 660.0kg., comparable to that of “Mibuyomogi” (A. maritima L.) and Kurram Santonica (A. kurramensis QAZ.). The santonin content was the highest (1.20%) in the plant collected on July 1, being better than that of “Mibuyomogi” (A. maritima L.). The plant, therefore, seemed to be of promise as the new source of santonin. 3) A. caerulescens var. angustifolia DC., obtained from Trieste, Italy, was almost or entirely devoid of santonin.