Examinations were made on the correlation between chemical structure of thiol esters and their corresponding related compounds and the biological activity centering around nematocidal activity, especially their action against insects, fungi, bacteria, and plant tissues. Examinations were also made on their action mechanism at the enzyme level. Tendency of nematocidal activity of R-COS-Ph(-Y) (A) and (X-)Ar-COS-Ph(-Y) (B) compounds examined by soaking method showed that phenyl thiobenzoate of (B) series had a stronger activity. Substitution of -COS-in (B) compounds with -COO- or -CONH- resulted in decrease of nematocidal activity. Substitution of phenyl in (B) series compounds with a hetero ring, such as thiophene and pyridine, resulted in strong efficacy. Comparison of the activity in various biological phases showed that these compounds have selective toxicity of considerable structural specificity in their toxicity against insects and plants. The compounds were also found to possess inhibition against alcohol dehydrogenase activity and histidine decarboxylase. This inhibitory effect is not nonspecific and it was assumed that the factor lies in the specific inhibition against SH enzyme.
Effect of medicinals on electrocardiographic tests was examined using pentobarbital-anesthetized normal and arteriosclerotic rabbits in order to develope a therapeutic agent for angina pectoris. Examinations were made on the acute effect of various medicinals as follows : (1) Hypoxemia test : ST depression at the time of low-oxygen laoding in arteriosclerotic rabbit; (2) Isoproterenol test : ST depression at the time of isoproterenol loading in mormal and arteriosclerotic rabbits; (3) Vasopressin test : ST and T elevation at the time of vasopressin loading in mormal rabbits; (4) coronary arterial ligation method : ST elevation by chronic coronary arterial ligation in normal rabbits; (5) RPQ index test : Measurement of RPQ index, which is an indirect index of oxygen consumption by myocardium, with each medicinal. The medicinals which showed some effect were adenosine, 4, 4'-(diethylaminoethoxy)hexoestrol, pronethalol, and iproveratril, in (1), 4, 4'-(diethylaminoethoxy)hexoestrol, propranolol, pronethalol, and iproveratril in (2), dipyridamol in (3), ATP, adenosine, 4, 4'-(diethylaminoethoxy)hexoestrol, and propranolol in (4), and ATP, dipyridamol, propranolol, 4, 4'-(diethylaminoethoxy)-hexoestrol, and nitroglycerin in (5).
Thiopental-35S having a specific radioactivity of 13.2 mCi/mmole was synthesized from H235SO4 as the starting material through H235S and thiourea-35S. Radiochemical and chemical yields from H235SO4 were 80.3 and 85.7%, respectively. The isotope dilution analysis for the determination of commercial thiopental sodium preparations was investigated with the 35S-labeled thiopental, and it gave the mean recovery of 99.60±0.68%. This method was advantageous over other known official methods such as ultraviolet absorptiometry and gravimetric analysis in the precision and selectivity of the method. As the metabolites of thiopental in the liver of male rats, methionine, thiourea, inorganic sulfate, and several unidentified 35S-containing compounds were recognized by radiopaperscannography or reverse isotope dilution method. Metabolic rates of thiopental-35S in rat liver were 0, 49.7, 59.2, and 60.2% at 15, 30, 90, and 120 minutes after its intraperitoneal injection, respectively. It was proved that a considerable amount of radioactivities arising from the injected 35S-labeled thiopental was distributed in rat brain within 15 minutes after its intraperitoneal adminstration, and that the rapid reduction in radioactivities was found to three-fifths of the original during the following 15 minutes.
Pharmacological examination was made on central effects of paeonol, which is a main component of the root bark of paeony (Paeonia moutan). This root bark is frequently used in home medicine and in oriental medicine as analgesic, sedative, antiinflammatory agent, hemostatic, and remedy for female diseases. Keishibukuryo-Gan ( ?? ?? ?? ?? ?? ) and Daiobotampi-To ( ?? ?? ?? ?? ?? ?? ) are frequent and representative prescription in which the root bark of paeony is cotained in about 20%. Mice were used for these tests and the following results were obtained in both intraperitoneal and oral administration of paeonol. The acute toxicity was low. Sedation (decrease of spontaneous motor activity and caffeine-induced hyperactivity) and hypnosis (loss of righting reflex) were recognized, the latter in higher intraperitoneal doses. Hexobarbital-induced anesthesia was prolonged. Analgesic activity was recognized in both the inhibition of writhing symptom induced with intraperitoneal administration of acetic acid and mouse tail pain by pressing. Hypothermia and antipyretic activity in typhoid-paratyphoid vaccine-febrile mouse were found. Anticonvulsive effect on maximal electroshock was obtained and moreover the same effect was also recognized on pentetrazol- and nicotine-induced convulsions. Thus, it was found that paeonol has many central depressive effects and the may be concerned with some parts of the therapeutic effects of paeony bark in oriental medicine.
Based on a previous work that the benzyne reaction of ortho-substituted halogenobenzenes with acetonitrile gave meta-substituted benzyl cyanides as an important starting material for the syntheses of isoquinolines in a comparatively good yield, the reaction of various ortho-halogenobenzenes with nitriles, except acetonitrile, was examined for the formation of the desired meta-substituted benzyl cyanides. In this case, meta-substituted amino compounds, formed by the addition of ammonia to the benzyne intermediate, was obtained as a by-product. The benzyne reaction of halogenobenzene with other nitriles, such as phenethyl cyanide, 2-phenyl-n-butyronitrile, methylene dicyanide, and isobutyronitrile, was carried out, but the expected compounds were not obtained. Reduction of 2-(3-methoxyphenyl)propionitrile and 2-(3-benzyloxyphenyl)propionitrile gave β-methyl-3-methoxyphenethylamine and β-methyl-3-hydroxyphenethylamine, respectively, which were used as the starting materials for the synthesis of isoquinoline. Several kinds of unknown isoquinoline derivatives were obtained by phenolic cyclization or by application of Bischler-Napieralski reaction through a few steps.
1) Azo compounds (II to VII) were synthesized by diazotization of 4-thiocyanotoaniline, p-chloroaniline, p-nitroaniline, and 2, 6-dichloro-4-nitroaniline, followed by coupling with p-chloro- or p-bromo-phenol, or 1- or 2-naphthol in neutral or weakly alkaline reaction. 2) Nitro compounds (VIII to XII) were synthesized by the reaction of 2, 4-dichloronitrobenzene with p-chloro-, p-bromo-, or p-fluoroaniline, p-methoxyaniline, and 2-amino-4-chloropyridine in pyridine solution. These nitro compounds were reduced with stannous chloride and hydrochloric aicd to the corresponding amino compounds (XIII to XVII), and further thiocyanated with ammonium thiocyanate to the thiocyano compounds (XVIII to XXII). 3) Antibacterial action of these azo, amino, and thiocyano compounds was tested in vitro. Further, pKα values of the 11 kinds of thiocyano compounds reported previously were measured to examine the relationship between these values and antibacterial action of these compounds.
Thermal treatment of xanthates bearing an anchimeric group in the neighborhood has been reported to cause rearrangement to dithiolcarbonates or trans-elimination depending upon their conformation (contrary to the Chugaev reaction).2a, b) In the present work, thionobenzoates were similarly treated and the analogous conclusion was gained concerning results and mechanisms. In addition, the identification of 2-dialkyl-aminoalkanethiol derivatives produced in this series of study was re-examined and Hansen's report9) on the same problem was corrected in the respects to isothiuronium salts formation and desulfurization reaction by Raney nickel.
The mass spectra of ibotenic acid(I), the pyro compound (5 -aminomethyl-3-hydroxyisoxazole)(III), and several 3-hydroxyisoxazoles are reported and discussed. Each fragmentation pathways are substantiated by exact mass measurements and deuterium labeling. The common features in 3-hydroxyisoxazoles in general are the prominent molecular ions and diagnostic fragment ions arising from the cleavage of the O-N and C(4)-C(5) bonds and/or from the eliminations of functional groups on the side chains and subsequent ring cracking. Unexpectedly, however, spectra of I and III, exhibited the formations of i3), i4, i7), and i9) ions, having no correlation with the fragments in common 3-hydroxyisoxazoles. The fragmentation mechanisms of these ions are also discussed.
The fragmentation patterns obtained by electron impact on thirteen 4-isoxazolin-3-ones are reported and discussed. The ion structures of each fragment have been substantiated by exact mass measurements and/or deuterium labelling. Subsequently, we established that six types of basic fragmentation modes occur : (a) O-N and C(4)-C(5) bonds cracking, (b) N-C(3) and C(5)-O cracking, (c) O-N and N-C(3) cracking accompanied with hydrogen rearrangement, (d) formation of d1) ion, (e) O-N and C(4)-C(5) cracking accompanied with rearrangement of C(5) substituents, (f) elimination of OH radical accompanied with rearrangement of C(5) substituents. The influences of C(5) substituents on the spectra are also discussed.
The mass spectra of 3-alkoxyisoxazoles have been examined. The basic fragmentation patterns have been substantiated by exact mass measurements and deuterium labelling. Several characteristic fragmentations and original rearrangement pathways depending upon the nature of C(3) and C(5) substituents are discussed. Formations of a2) and a3) ions produced by the O-N and C(4)-C(5) bonds cracking are more prominent in 3-methoxy-isoxazoles. In 3-ethoxyisoxazole, the eliminations of ethylene molecule, e.g. McLafferty rearrangement, are predominant. On the other hand, in 3-benzyloxyisoxazole, there is a remarkable rearrangement of benzyl group to the 2-position and every fragment is possibly connected with corresponding 2-benzyl-4-isoxazolin-3-one.
Various reaction conditions were examined for the formation of II, III, IV, and V by the application of hydrogen peroxide to 1, 6-naphthyridine in acetic acid solution. Infrared, ultraviolet, NMR, and mass spectra of these four compounds were measured to presume their structure, which was determined by chemical methods such as reduction with Raney nickel. Structure of one of these compounds was estimated. Antibacterial action of II, III, and IV was also examined.
Comparative examinations were made on the antibacterial action of 3-methoxy-2-phenoxybenzaldehyde and 21 kinds of its derivatives, 3-methoxy-4-(3-methoxyphenoxy)-benzaldehyde and 22 kinds of its derivatives, and 3-methoxy-4-(4-methoxyphenoxy)-benzaldehyde and 23 kinds of its derivatives against sensitive strain of human tubercle bacilli H37Rv, using Tween-albumin medium. Comparison of 3-methoxy-4-phenoxy-benzaldehyde derivatives reported previously1)and the present series of compounds showed that in compounds with one methoxyl, presence of a phenoxy group para to the formyl group had better antibacterial activity than those with the phenoxyl ortho to the formyl group. Compounds with two methoxyl groups had lower antibacterial activity than those with one methoxyl. In the series of compounds reported in the present paper, with the same skeleton on the right-hand side, the compounds possessing a methoxyl meta to the bridged oxygen showed an antibacterial activity while those with methoxyl para to the bridged oxygen hardly showed any activity. The thiosemicarbazones of the three compounds reported in the present series showed no increased antibacterial action by substitution of the hydrogen in 4-position of the thiosemicarbazono group with alkyl or aryl but such increased antibacterial action was observed in the case of 3-methoxy-4-phenoxybenzaldehyde thiosemicarbazone reported previously.1)
From the comparison of the CD curves of (+)-hesperetin (IV) and (-)-hesperetin (V) of known steric configuration with those of protofarrerol (I), farrerol (II), and dihydroprotofarrerol (III), and based on the general rule regarding steric configuration of aryl ketones by CD curves, the steric configuration of the C-2 position in I, II, and III was clarified to be in S-configuration. It was further presumed that the C-1' position in I has the R-configuration from the examination of its CD curve, based on the hypothesis that there is an additivity in the two conjugate systems of 4-chromanone and cyclohexenone systems of I.
The flavonoid and xanthone constituents of Swertia randaiensis HAYATA (1) and S. swertopsis MAKINO (2) were examined. A new xanthone O-glycoside, named norswer tianolin (VII), C19H<18>O<11>, mp 265° (decomp.), was isolated from 1. The hydrolysis of VII with diluted acid produced desmethylbellidifolin (V) and glucose. The position of sugar bonding was proved to be on 1-position since, methylation of VII with diazome thane and subsequent hydrolysis afforded 1-hydroxy-3, 5, 8-trimethoxyxanthone. The structure of VII was therefore found to be desmethylbellidifolin-1-O-glucoside. From 2, norswertianin (I), swertianin (II), methylswertianin (III), decussatin (IV), methylbellidifolin (VI), isovitexin (IXa), homo-orientin (XIa), and mangiferin (XVa) were isolated and identified.
Effect of nonionic surface active agent (lauric diethanolamide; HS-12-P) and the effect of the concentration of hydrocortisone acetate-4-14C on the release of hydrocortisone from liquid vehicle to the human excised skin are described. The relationship between the release of hydrocortisone acetate and concentration of HS-12-P to the excised human skin was observed as shown in Fig.1. The results showed that the rate of the release of hydrocortisone acetate was increased with increasing concentration of HS-12-P up to 7% but, above that concentration, the rate was reduced. This reduction depends on the entrapment of hydrocortisone acetate in micelles. The rate of release of hydrocortisone acetate increased proportionally with increasing concentration of hydrocortisone acetate when using a liquid vehicles, i.e., liquid paraffin (Fig. 5), propylene glycol (30%) -H2O (70%) (Fig. 3), and HS-12-P (10%) -H2O (90%) (Fig. 4). It was suggested that the proportional relation between the concentration and rate of release of hydrocortisone acetate was not related to the solubilities of hydrocortisone acetate in each liquid vehicles.
The biological effects of surfactants are only partially understood. To clear some of mechanisms of enzyme activation and inhibition by surfactants, the effect of surfactants of various types on Mucor lipase was examined. Anionic surfactants had a strong inhibitory effect on the lipase in both of enzyme system and reaction system. However, surfactants in a certain concentration partially accelerated lipolysis and this concentration was generally equivalent to one-half the critical micelle concentration (c.m.c.) in a reaction mixture. All cationic surfactants were found under certain conditions to enhance the rate of hydrolysis of olive oil. The concentration of surfactants which gave the most powerful stimulation was 0.0055% (w/v) for benzalkonium chloride, 0.0065% for benzethonium chloride and 0.004% for cetylpyridinium chloride in the reaction system, but more concentrated solutions of them caused inhibition. The increase of hydrolysis rate was found to depend essentially on the oil/surfactant ratio, and a small amount of the surfactant caused an increase in the lipase adsorption at oil-water interface. Both nonionic and amphoteric surfactants enhanced the rate of lipolysis till their concentration reached about one-half the c.m.c. However, the surfactants in c.m.c. and more concentrated solution caused strong inhibition. The preincubation of the enzyme with either nonionic or amphoteric surfactant solution resulted in the increase of the lipase activity and its adsorption at oil-water interface.
Measurement of dissolved oxygen was carried out by the carbon dioxide evolution method and by gas chromatography on various concentrations of mixtures of nine kinds of solubilizing agent and water. In mixtures of ethylene glycol, diethylene glycol, triethylene glycol-H2O, having a hydrophilic group, and water, dissolved oxygen was found to decrease with increasing concentration of these agents. In contrast, aqueous mixtures of Cellosolve, Butyl Cellosolve, Carbitol, Butyl Carbitol, hexylene glycol, dipropylene glycol-H2O, having both hydrophilic and hydrophobic groups, showed a minimum point in the content of dissolved oxygen, and its amount increased above that point, and the agents alone, without the presence of water, was found to have the largest content of oxygen. In these mixtures, function of the solution to dissolve oxygen decreased at the concentration of the minimum point.
Aqueous extract of the air-dried leaves and branches of Quercus stenophylla MAKINO (Japanese name "Urajirogashi") was treated with a solution of lead acetate and the precipitate formed was filtered off. The filtrate was passed through ion exchange columns and successively chromatographed on charcoal-Celite to be isolated into scylloinositol (I), proto-quercitol (II), D-glucose (III) and D-fructose (IV). These compounds were also separated and identified by gas-liquid chromatography.
9-Chloro-1, 2, 3, 4-tetrahydroacridine 10-oxide was obtained in relatively good yield from 9-chloro-1, 2, 3, 4-tetrahydroacridine through N-oxidation with permaleic acid. Nitration of 1, 2, 3, 4-tetrahydroacridine 10-oxide gave 9-nitro-1, 2, 3, 4-tetrahydroacridine 10-oxide, which was further treated with concentrated hydrochloric acid to give the 9-chlorinated N-oxide compound. The ultraviolet and infrared absorption spectra of both products are presented.
Separation and determination of L-ascorbic acid and D-araboascorbic acid in their mixed aqueous solution were carried out by gas-liquid chromatography, using transformation of these compounds into trimethylsilyl (TMS) derivatives. Silylating agents used were hexamethyldisilazane and trimethylchlorosilane. A gas chromatograph equipped with hydrogen flame ionization detector was used and the peak area ratio method was applied, employing 2-naphthol as the internal standard. The support, which contained 5% by weight of Apiezone grease L (on silanized Chromosorb W, 80-100 mesh), was packed into a U-shaped stainless steel column, 3 mm in diameter and 3 m long. The flow rate of nitrogen as a carrier gas was 14 ml/min. The column temperature was 250°. The total amounts of L-ascorbic acid and D-araboascorbic acid obtained by gas-liquid chromatograph were in good agreement with those obtained by iodometry.
Examinations were made on the alkaloidal components in the trunk wood of Actinodaphne acutivena (HAYATA) NAKAI (Japanese name 'Nagami-kurodamo') and in the trunk bark and wood of Litsea hayatae KANEHIRA(Japanese name 'Hirohadamo') (Lauraceae). Laurolitsine (I) was isolated and identified from the former, and I, ushinsunine (II), and liriodenine (oxoushinsunine) (III) from the latter.
Examinations were made on the methods for tritiating a specific position of the benzene ring in the carcinogenic quinoline derivative, 4-nitroquinoline 1-oxide. Each of the tritiated quinolines, which were obtained by the catalytic hydrogenation of 5-, 6-, 7-, and 8-bromoquinolines with tritium over palladium black, was oxidized with perbenzoic acid and nitrated with potassium nitrate. The loss of tritium under these conditions was only 2%. The labeled position was proved by the infrared and nuclear magnetic resonance spectra of deuterized quinolines which were prepared under the same conditions as for the tritiated compounds.