In order to find some pharmaceutics which has weak hypertensive and cardiostimulation action, and powerful tonsil expansion, anticonvulsant, and anti-allergic actions, derivatives of N-alkyl-1, 5-dimethylhexylamine were prepared and their action of slackening excised tracheal muscle of a guinea pig and their acute toxicity were tested. In general, efficacy was stronger in monoalkylamines (propyl, isopropyl, butyl, isobutyl) than dialkylamines (dimethyl, diethyl, piperidyl), and all were stronger than ephedrine although they were less effective than epirenamine and diphenhydramine. Toxicity was stronger in monoalkylamine than dialkylamine and among the monoalkylamines, the iso types were less toxic than the normal type.
Pharmacological activities in general were tested with N-isopropyl-1, 5-dimethylhexylamine hydrochloride (No. 4). The antiacetylcholine and antihistamine actions of No. 4 on excised tracheal muscle of a guinea pig were 10 times that of ephedrine and their anti-barium action was one-half that of papaverine. Similarly, antiacetylcholine and antihistamine actions on excised intestine were 2 and 100 times respectively that of ephedrine, and anti-barium action was one-tenth that of papaverine. The compound No. 4 indicated hypotensive and cardiac inhibitive actions and this point differs from the known alkylamines and aralkylated sympathomimetic amines. Its action on peripheral vessels, pupil, and saliva secretion was very weak. Its effect in preventing histamine shock was less than that of Diphenhydramine but better than that of ephedrine or methoxyphenamine.
Some analytical conditions for the determination and distinction of alkoxyl groups by the combustion method are discussed. The required temperature of silver gauze for absorbing iodine quantitatively is 150°. At this temperature, silver gauze quantitatively absorbs iodine which corresponds to 45% of the weight of the silver gauze. The temperature for complete combustion of methyl and ethyl iodides with platinum contact in air stream is 700°. The distillation time of methyl iodide is 10 minutes and that of ethyl iodide is 20 minutes, but it seems a little longer time than that is necessary when the reaction mixture containing a large amount of organic solvent is used to hydrolyse the sample.
2-(3-Ethoxypropionyl) cyclopentanone (XIII) was prepared by the application of 3-ethoxypropionyl chloride to 1-piperidinocyclopentene (XVIII) and (XIII) was hydrolysed by alkali into 8-ethoxy-6-oxoöctanoic acid (XV). Keto acids (XV) easily change into the methyl ester (XX) with diazomethane and esterification with alcohol, benzene, and sulfuric acid resulted in exchange reaction between the ethoxyl at 8-position with alcohol.
2-(3-Ethoxypropionyl) cyclopentanone (III) was prepared by application of 3-ethoxypropionyl chloride (II) to 1-morpholino-(I:R1, R2=-(CH2)2-O-(CH2)2-), 1-(1-pyrrolidinyl)-(I:R1, R2=-(CH2)4-), and 1-dibutylaminocyclopentene (I:R1, R2=C4H9-). 2-(3-Alkoxypropionyl) cyclopentanones (IX) were prepared by application of 3-methoxy-(VIII:R=CH3-), 3-propoxy-(VIII:R=C3H7-), and 3-butoxy-propionyl chloride (VIII:R=C4H9-) to 1-piperidinocyclopentene (I:R1=R2=-(CH2)5-). These β-diketones (III and IX) form copper chelates (IV and X) and convert into 8-alkoxy-6-oxoöctanoic acids (VI and XI). Several kinds of new methyl 8-acyloxy-6-oxoöctanoates (XIV) were prepared by addition of fatty acid to methyl 6-oxo-7-octenoate (XIII).
In order to examine reproducibility of Rf values in paper chromatography, the most common partition chromatography was carried out on Zaffaroni-type impregnated filter paper and two-componental solvent system. Following conclusions were made on the cause of variation in Rf values and the method of correcting it. Seven factors were given as the cause of variation: (i) Temperature, (ii) characteristics of the filter paper, (iii) adsorption of filter paper, (iv) composition of the stationary phase and mobile phase, (v) volume ratio (Vs/Vm) of stationary phase and mobile phase in unit weight of the filter paper, (vi) atmospheric humidity, and (vii) uniform distribution of the stationary phase. It was found that this volume ratio, Vs/Vm, is the main factor of variation if the temperature is kept constant and could be taken as the standard of correction. In order to calculate this volume ratio, rate of void space of the filter paper was considered and this was measured with three kinds of solvent. It was thereby found that the use of a solvent with different degree of swelling filter paper fiber gave different rate of void space. Effect of humidity on impregnated paper was observed through weight variation and it was found that it is necessary to carry out drying procedure in high humidity and that impregnation in a solvent containing water (including reversed-phase chromatography) made it impossible to obtain constant Rf values. In order to have the filter paper retain the stationary phase uniformly, it was necessary to soak the filter paper in the solution horizontally for 10-20 minutes and treated rapidly in horizontal position. Correction formula (equation (5)) for Rf values was established and the value was converted to Rfu value (Rf value where Vs/Vm=1/2) by interpolation of the calculated values for Vs/Vm. Since this is a small value of variation, this correction formula was considered to be appropriate in the range where adsorption can be neglected. According to this formula, it is possible to calculate the Rf value in accordance with variation in Vs/Vm on the basis of Rfu value and to remove the difference in filter papers with different rate of void space. Further, it is considered that this formula is applicable to non-impregnated paper.
In order to elucidate the solubilization phenomenon of non-electrolyte solid pharmaceutics, heat of sublimation, heat of melting, and solubility of pyridine and pyrazinemonocarboxamides were measured. In the present series of work, heat of solution in water, methanol, methyl acetate, and chloroform was measured, heat of solvation was calculated from its result, and some considerations were made.
It was found that application of thionyl chloride to p-hydroxy- or p-benzyloxy-benaoic acid sometimes resulted in formation of a polyester, same as in the case of previously reported vanillide and tetravanillide. In addition, it was found that the formation of polyester depended on the properties of thionyl chloride used, the polyester being formed when thionyl chloride used was left in a clear glass ampule under irradiation of sunlight over a long period of time or irradiated with ultraviolet ray. It follows, therefore, that preparation of acid chloride should be carried out in the presence of pyridine or by the use of thionyl chloride preserved under protection from direct sunlight.
(-)-Menthyl and (+)-bornyl pyruvates, and (-)-menthyl and (+)-bornyl phenylglyoxylates were reacted respectively with ethynyllithium or 2-phenylethynyllithium, followed by reduction and hydrolysis to form atrolactic acid homologs. The optical rotations of these four products were compared with those of the same atrolactic acid homologs obtained by reaction of the foregoing four keto esters with ethyl- or phenethyl-magnesium bromide. The levorotatory compound was fractionated from dl-2-ethynyl-2-phenylglycolic acid and its reduction afforded (-)-2-ethyl-2-phenylglycolic acid. This starting acid and the product were proved to have the same configuration. The foregoing four keto esters were reacted with ethynyllithium and hydrolyzed without reduction. The optical rotations of the atrolactic acid homologs with a triple bond so obtained were compared with those of the products obtained as above and ethynyllithium was found to have the same reaction orientation properties against the carbonyl as alkylmagnesium bromide. By the use of the present method, the hydroxyl group in 3-position of cyclolaudenol was directly proved to be the L-series as had been assumed to date and it was also proved by the present series of work that ethynyllithium can be used for determination of absolute configuration by the Prelog method.
Four kinds of α-keto ester, (-)-menthyl pyruvate, (+)-bornyl pyruvate, (-)-menthyl phenylglyoxylate, and (+)-bornyl phenylglyoxylate, were reacted with ethynyl-magnesium bromide and the product was hydrolyzed. The optical rotation of atrolactic acid possessing a triple bond so obtained was compared with that of the hydroxy acid obtained by reaction of the foregoing α-keto acids with ethylmagnesium bromide. It was found in the two kinds of pyruvate that ethynyl- and ethyl-magnesium bromides gave atrolactic acid derivative with opposite optical rotation and it was thereby concluded that these two reagents attacked the carbonyl in pyruvate from opposite directions. This fact clearly indicates that ethynyl group is spatially smaller than the ethyl group.
Two new substances, neoastilbin (II) and isoastilbin (III), were obtained by heating astilbin ((+)-dihydroquercetin 3-L-rhamnoside) (I) with 10% pyridine water for a few hours or by heating in water for 40-50 hours and fractional crystallization of the residue, obtained after evaporation of the solvent, from 30% ethanol. Another new substance, neoisoastilbin (IV), was obtained on application of ethanolic sodium acetate solution to (I) (cf. Table I). All (I), (II), (III), and (IV) afforded quercitrin (quercetin 3-L-rhamnoside) on dehydrogenation and 2′-hydroxy-α-(L-rhamnosyioxy)-3, 4, 4′, 6′-tetramethoxychalcone by application of hot alkali solution to the respective tetramethyl ethers formed by reaction with ether solution of diazomethane (cf. Chart 1). These facts indicate that (II), (III), and (IV) are dihydroquercetin 3-L-rhamnoside, same as (I), and are considered to be stereoisomers arising from asymmetry at 2- and 3-positions in the aglycone.
Hydrolysis of astilbin (I), neoastilbin (II), isoastilbin (III), and neoisoastilbin (IV) with 5% sulfuric acid affords one mole each of L-rhamnose and dihydroquercetin, the aglycones of (I) and (IV) being obtained as the dextrorotatory trans-type and those of (II) and (III) as levorotatory trans-type (cf. Tables I and II). Application of ethanolic sodium acetate solution to (I) affords (IV) and further application of the same reagent to (IV) gives (I). Application of the same reagent to (II) affords (III), and vice versa. This change is considered to be a phenomenon arising from inversion of the conformation of 3-OR (R=L-rhamnosyl) by enolization of the carbonyl in the aglycone. It is therefore assumed that (I) is (+)-dihydroquercetin 3-L-rhamnoside, (II) is (-)-dihydroquercetin 3-L-rhamnoside, (III) is probably (-)-epi- or -cis-dihydroquercetin 3-L-rhamnoside, and (IV) is probably (+)-epi- or -cis-dihydroquercetin 3-L-rhamnoside.
The chalcone glycoside, prepared by ring cleavage of tetramethylastilbin, was heated with 10% pyridine water for a long period of time and afforded tetramethylastilbin and an amorphous substance which was assumed to contain chiefly tetramethylneoastilbin. Treatment of astilbin (I) with hot, conc. alkali solution is thought to cause initial ring cleavage to form the chalcone glycoside (XII) whose isolation is difficult. Similar to the case of isomerization of (I) by hot 10% pyridine water, neoastilbin (II), isoastilbin (III), and structurally unknown chalcone compound are isolated, besides (I), in this case. The spot corresponding to that of neoisoastilbin (III) was detected in the paper chromatogram of this product. Isomerization of (I), (II), (III), and (IV) is thought to be due mostly to inversion of the conformation of 3-OR (where R is L-rhamnosyl) by enolization of the carbonyl in the aglycone, as stated in the preceding peport, but it may be considered that the extremely unstable (XII) is an intermediate in this reaction and various isomers are formed during recyclization (cf. Chart 1).
Antimicrobial activity was examined with cycloheximide, its isomers and derivatives, and related substances including ψ-cycloheximide. Discussions were made on the correlation between the structure and activity of cycloheximides. Some mention was made on the synthesis of N-methylcycloheximide.
The pyrimidine portion of thiamine, 2, 5-dimethyl-4-aminopyrimidine (I), shows one-step reduction wave in E1/2=(-1.06-0.076 pH) at pH 1-8. Its diffusion current constant, kD, is 4.8 (μA⋅mM-1⋅mg.-2/3⋅sec.1/2) at pH 3-6, and becomes one-half at pH 8. This reduction wave is due to hydrogenation of the proton adduct of (I) in the course of three-electron reduction. The formation of ammonia and amine was observed by controlled potential electrolysis. The thiazole portion of thiamine, 3, 4-dimethyl-5-(2-hydroxyethyl) thiazolium iodide (II), undergoes electrolytic reduction at pH 6.8 to be decomposed into hydrogen sulfide, amine, alcohol, and sulfur-containing compound. Cathodic wave of E1/2 -1.4V and kD 8.6 is due to reduction of the thiazole ring and the cathodic wave of E1/2 -1.7V is ascribed to catalytic hydrogen wave of the reduction product. (II) takes the thiol type at pH above 9 and shows anodic wave (E1/2 -0.43V) due to the reaction of thiol-+Hg→ thiol-Hg+e. From the ie-pH and titration curves, pK of the thiol type was calculated as 10.3. Formation velocity of the thiol type is proportional to the concentration of OH- and k1 is 0.18 (min.-1) at pH 10.5. The reaction of the thiol type and p-chloromercuribenzoate, and oxidation of thiol type to the disulfide were examined by polarography.
Principle of polarographic waves indicated by thiamine under various conditions have been revealed. The cathodic wave of E1/2 -1.1V at pH 1 has the properties of a diffusion current and shows diffusion current constant, kD, of 12.5 (μA⋅mM-1mg.-2/3⋅sec.1/2) and its temperature coefficient is 1.8% deg-1. This is due to electrolytic reduction of the thiazole and pyrimidine rings, and hydrogen sulfide, ammonium chloride, and 3-acetyl-3-mercapto-1-propanol are obtained by the controlled potential electrolysis. This wave height decreases with increasing pH above 5. This wave is ascribed to reduction of the cation of thiamine. The anodic wave (E1/2≅Ep=-0.32, -0.4V) indicated by the thiol-type thiamine in alkaline solution at the dropping mercury electrode is due to the formation of mercurithio thiamine and the wave of Ep -0.14, -1V, is due to adsorption and desorption of thiol-type thiamine. The anodic wave at +0.2V shown by thiamine mononitrate in acid solution at the dropping mercury electrode is due to formation of thiamine mercury (I) complex. The use of rotating platinum electrode gives the oxidation wave due to 2B1-S-→ thiamine disulfide+2e at E1/2+0.3V. From its wave height-pH curve, apparent pK′ 10 is calculated. The greater value of pK′ than pK 9.33 for the thiol-type thiamine is considered to be due to kinetic current.
Eight kinds of papaveraceous plants growing wild in Japan were examined with dilute ethanolic extract for total crude alkaloid content, for papaverine-like antispasmodic action, using mouse intestine and guinea pig trachea, and median lethal dose in mice. Further, antispasmodic action of the crude total alkaloid extracted from the ethanolic extract was also examined. The content of total crude alkaloid was the highest in Pteridophyllum racemosum and lowest in Chelidonium japonicum var. typicum. Antispasmodic action of the extract was generally stronger in the trachea than in the intestine, being the strongest in P. racemosum and weakest in Ch. majus. Ch. japonicum var. typicum alone showed contracting action. The antispasmodic action of the alkaloidal fraction was 15-30% of papaverine hydrochloride in all of the eight plants. Toxicity was the strongest in C. decumben and weakest in Ch. majus.
A solution of α-lipoic acid and thiourea dissolved in butanol, with application of heat, when allowed to cool gradually, precipitates a crystalline addition compound. The analytical values of this addition compound suggest that it is composed of one mole of α-lipoic acid and 6.3 moles of thiourea. Ultraviolet spectrum, polarography, and biological activity all give values corresponding to this composition. The X-ray diffraction pattern of the adduct differs from those of α-lipoic acid, thiourea, or cyclohexane-thiourea adduct. Its lattice constants indicate that the adduct is monoclinic, differing from the rhombohedral form of the thiourea adduct. Infrared absorption spectrum of the adduct is almost the same as those of the known thiourea adducts except that the absorption of carbonyl of lipoic acid in the adduct is the same as that of lipoic acid in carbon tetrachloride solution, indicating that there is no interaction between lipoic acid molecules. Lipoic acid in this adduct is stable and does not change after 30 days at 38° in 92% relative humidity. Washing of this adduct with ethanol results in dissolution of lipoic acid and a part of thiourea remains as a rhombic thiourea. The adduct is also formed by standing a mixture of lipoic acid, thiourea, and a small quantity of methanol in a sealed vessel at 40° for four days. These facts suggest that α-lipoic acid-thiourea adduct is a new type of inclusion compound.
The water-soluble quaternary base, phellodendrine, contained in Phellodendron amurense RUPR. (Japanese name ‘Kihada’) and Ph. amurense var. sachalinense FR. SCHM. (Japanese name ‘Hiroha-kihada’), had been shown to have a structure corresponding to L(-)-N-methylcoreximine (VIII). In the present series of work, 3, 10-dimethoxy-7-methyl-5, 6, 13, 13a-tetrahydro-8H-dibenzo a, g quinolizine-2, 11-diol (VIII), its O, O-diethyl derivative (IX), and its methine base (X) were prepared by the route shown in Chart 1 and the compounds synthesized were identified with the natural phellodendrine and its corresponding derivatives. This has proved beyond doubt that phellodendrine has the structural formula (VIII) as had been presumed. On the other hand, Manske had proposed the formula (VII) for the tertiary phenolic base, coreximine, isolated from Dicentra eximia, based on its decomposition reactions and from biogenetic consideration of this kind of bases in the plant. The structure of coreximine was also found to be correct by the preparation of the substance (VII) in the present series of work. In this connection, an isomer of phellodendrine, dl-3, 11-dimethoxy-7-methyl-5, 6, 13, 13a-tetrahydro-8H-dibenzo [a, g] quinolizine-2, 10-diol (VIIa), was also synthesized.
In continuation of previous works, isomers of dl-phellodendrine (I), differing from it in the position of two methoxyl and two hydroxyl group, were synthesized as dl-3, 11-dihydroxy-2, 10-dimethoxy-(IX) and dl-3, 10-dihydroxy-2, 11-dimethoxy-7-methyl-5, 6, 13, 13a-tetrahydro-8H-dibenzo [a, g] quinolizinium iodide (IXa).
Opium alkaloid injection containing atropine was submitted to separatory analysis. Atropine and morphine were separated by column partition chromatography, atropine was determined by colorimetry, and morphine by nonaqueous titration. Satisfactory results were thereby obtained. Gist of separation procedures is indicated in Charts 1-3.
Separatory determination of morphine and scopolamine in the opium alkaloid injection containing scopolamine was carried out. Morphine and scopolamine were separated by column partition chromatography by the procedures illustrated in Chart 2, morphine was determined by nonaqueous titration and scopolamine by colorimetry. Satisfactory results were obtained.
Polarographic behavior of six kinds of α-hydroxyimino-fatty acid was examined and their reduction mechanism was examined by the controlled potential electrolytic reduction, α-Hydroxyimino-fatty acids show distinct one-step wave in strongly acid solution and its electrolytic reduction mechanism was found to be the four-electron reduction of the hydroxyimino group in non-dissociated acid to amino group, forming the corresponding α-amino acid. By the use of this reaction, controlled potential electrolysis of α-hydroxyimino acid was carried out in strongly acid solution, with mercury cathode, and six kinds of corresponding α-amino acid were obtained in 97-98% yield. The use of lead cathode resulted in considerable decrease in the yield and current efficiency. For quantitative determination of α-hydroxyimino-fatty acids, the best result was obtained by carrying out the reaction at pH 2.
Twenty-one anticancer agents were submitted to the test for some specific inhibitory effects on the syntheses of nucleic acid and of protein by and on respiration of E. coli. Mitomycin, RC-4, and nitrogen mustard showed specific inhibitory effect on DNA synthesis. Among them mitomycin showed a lethal activity on bacterial cells in the resting stage even in a concentration of 0.01γ/cc. 4-Nitroquinoline 1-oxide and 5-methyltryptophan showed specific inhibitory effects on syntheses of RNA and protein. In addition to chloramphenicol, 5-nitro-2-furylacrylate and actinomycin showed a specific inhibition on protein synthesis in a limited range of their concentrations.
It has been found that the two split absorption bands observed in 1, 3-cyclohexanediones in dilute chloroform solution originating in the C=O stretching of the free diketone were found to give constant values for the distance between the two bands, ν1 and ν2, and the ratio of their intensity, without being affected by the substituent in the 4-position. Consequently, these two bands were assigned to splitting due to resonance coupling of C=O stretching vibration.
The enol compound of 1, 3-cyclohexanediones in dilute chloroform solution forms a dimer merely by intermolecular hydrogen bonding and with increasingly higher concentration toward the solid, a conjugated chelate system is formed. In such a case, two absorption bands were observed in the C=O stretching region and these were assigned to the coupling vibration by averaging the force constants of C=O and C=C bonds. The intensity of this in-phase vibration was found to be proportional to the Hammet's constant of 4-substituent.
The position of OH stretching band of 1, 3-cyclohexanedione derivatives with carbonyl group in 2-position was not identified against the conjugated chelate system in their enol compound. The characteristic wave form in the νC=O region was considered to be due to the cis configuration of the C=C and C=O bonds originating in the exo-ethylenic form of the enol compound.
Of the three absorption bands, ν1, ν2 and ν3, present in the region of 1600-1500cm-1 in α, β-unsaturated β-amino-ketones formed by substitution of enolic hydroxyl in 1, 3-cyclohexanediones with anilino, benzylamino, and phenethylamino group, ν3 corresponds to the amide-II band in the secondary amide, and ν1, and ν2 were considered to be explanable in a same manner as the coupling vibration of C=O and C=C described in Part I of this series. The intensity of this in-phase vibration was found to be proportional to the aromaticity of the substituted amines.
Infrared spectra of 1, 3-cyclohexanedione derivatives in dioxane solution were measured. It was found that the enol compounds of these derivatives underwent intermolecular hydrogen bonding with dioxane, by which dimerization was inhibited. The infrared spectra on did not show the coupling vibrations (ν3, near 1610cm-1 and ν4, near 1560cm-1) present in the solid and two sharp absorption bands were observed for νC=O at 1640-1656cm-1 and for νC=C at 1609-1612cm-1. The position of νC=O indicated linear relationship with Hammet's constant σ but there was no marked difference in intensity ratio between that and νC=C. Similar examinations were made on 3-anilino-2-cyclohexenone derivatives and the infrared spectra showed the absence of characteristic bands of the solid at 1610 and 1575cm-1, and two sharp absorption bands of νC=O at 1628-1638cm-1 and νC=O at 1590cm-1 were observed.
Infrared absorption spectra of 1, 2-cyclohexanedione, the representative cyclic α-diketone, and its deuterated compound were examined and it was found from the positions of OH and OD bands that there is no strong interaction here corresponding to the conjugated chelation in β-diketones. From the comparison with the result of measurement on diosphenol by Févre, et al., and from the result of dilution with chloroform, the C=O stretching vibration at 1735cm-1 in the spectrum of 1, 2-cyclohexanedione was assumed to be due to the presence of a diketo form. From the behavior of absorption bands in the region of 1500-1680cm-1 in 2-anilino-2-cyclohexen-1-one, there was no marked resonance effect such as seen in α, β-unsaturated β-aminoketones.
Amount of creatinine in the 24-hour urine was measured in healthy children, during normal time and after administration of a drug, and it was found that there was almost no variation in the value. Amino-nitrogen and glucuronic acid in the urine were measured after administration of sodium glutamate in healthy children and variation in creatinine ratio in both cases was examined. The ratio tended to increase after administration but the value gradually returned to the original with passage of time.
In order to examine the properties of 1, 2-dihydroisoquinoline derivatives, 2, 3-dimethyl-6, 7-methylenedioxyisoquinolinium iodide was reduced with lithium aluminium hydride to form the corresponding 1, 2-dihydroisoquinoline derivative and the latter compound was identified with the picrate of a sample prepared by a different route. It was also found that this substance is comparatively unstable in air.
An antitumor substance, mercury-hematoporphyrin complex (MH), now being tested for clinical use in Japan, was retested for antitumor activity in animals employing solid-type of Ehrlich ascites tumor cells. In Method I, a slight modification of Sugiura's method, MH showed no antitumor activity, while in Method II where the drug was given beginning at 7 days after the inoculation of cancer cells, it showed a marked effect. MH gave no effect against Ehrlich ascites cells.
Two kinds of 2-alkyl-2-picolylmalonate (Ia and Ib), and two kinds of 2-alkyl 2-lutidylmalonate (Ic and Id) were prepared by condensation of diethyl 2-methyl- or 2-ethylmalonate and ω-chloro-2-picoline or ω-chloro-2, 6-lutidine. Treatment of these compounds with urea or thiourea afforded the corresponding barbituric acid derivatives (IIa to IId) or thiobarbituric acid derivatives (IIIa to IIId). Reaction of the latter compounds (IIIa to IIId) with Raney nickel gave the corresponding dioxo-hexahydropyrimidine derivatives (IVa to IVd). These 12 kinds of new compound did not show the anticipated hypnotic action but some of them showed sedative or stimulating activity.
Pale yellowish white microneedles, m.p. 250-251°, m.p. 253-254°, and m.p. 253-254°, were isolated in respective yield of 1.3%, 1%, and 0.8% from the leaves of Cirsium kagamontanum NAKAI, MAKINO, and C. inundatum MAKINO. These three substances were all identical and showed tendency to undergo gelation in the presence of water, and were determined as pectolinarin (6, 4′-dimethoxy scutellarein 7-rhamnoglucoside). The leaves of C. matsumurae NAKAI var. pubescens KITAMURA afforded pale yellowish white microneedles, m.p. 249-250°, in 0.06% yield and this was identified as luteolin 7-glucoside.
Five kinds of domestic Diospyros genus trees are known; D. Kaki L., D. Kaki var. silvestris MAKINO, D. Lotus var. glabra MAKINO, D. Lotus var. typica MAKINO, and D. Morrisiana HANCE. The leaves of D. Kaki afforded pale yellowish white microneedles, m. p. 218-220°, in 0.02% yield and the leaves of D. Lotus var. glabra afforded slightly yellowish brown scales, m. p. 193-194°, in 0.15% yield. The former was identified as astragalin (kaempferol 3-glucoside) and the latter as myricitrin.
The mother liquor, left after separation of phellodendrine (L-(-)-N-methylcor-eximine) (I) extracted from Phellodendron amurense RUPR., was examined and can-dicine (II) was isolated as crystalline iodide in 0.01% yield against the original plant.
Examination were made for alkaloids contained in Formosan Mahonia lomariifolia TAKEDA (Japanese name “Arisan-hiiraginanten”) and M. Morrisonensis TAKEDA (Japanese name “Niitaka-hiiraginanten”). It was thereby found that both plants contained the same tertiary and quaternary bases, as shown in Table I, and that there is some difference in the alkaloid present in these plants according to habitat, as indicated in Table II on comparison of Japanese, Formosan, and Indian Mahonia genus plants.
The commonly used Goldenberg method for analysis of. tartar is comparatively complicated in procedures and the end point of titration is not so clear. A simple and precise determination of total tartaric acid was established by the use of strongly acid, cation exchange resin. This procedure also makes it possible to carry out simple determination of calcium in the effluent. The experimental results are shown in Tables I and II.
Several series of compounds were found to have strong activity by the in vitro screening of 1, 300 organic compounds against tumor cell by the cell-agar plate method. Among these series of compounds, amino acid analogs and their related acylamino compounds were tested for the antitumor activity by the solid type Ehrlich ascites carcinoma in mice. Some methionine analogs showed marked effect against the tumor cells.
As one of the processes for preparation of hesperetin 7-glucoside, partial hydrolysis of 3′-ethoxycarbonylhesperidin (III) or acetylhesperidin (IV) was carried out. Boiling of (III) in ethanol solution with sodium acetate resulted in liberation of the ethoxycarbonyl group and ethanolic solution of hesperidin was obtained. Partial hydrolysis was effect by heating this ethanolic solution or ethanolic solution of (IV) with hydrochloric acid for about 1 hour, affording (I), m. p. 204.5-205.5°, in ca. 15% yield.