Effect of aminoacetonitrile on hepatic injuries by treatment of rats with carbon tetrachloride was tested. The possible participation of the sympathetic nervous system in the development of fatty liver was also examined. A long-lasting elevation of free fatty acids was observed in plasma of rats after an administration of CCl4. The increase of plasma fatty acids and liver lipid by CCl4 was partially prevented by dibenzyline, propranolol, and trimethidium. The fatty liver produced by CCl4 was markedly potentiated by phenelzine but not by pyrogallol. When 50 to 100 mg/kg of aminoacetonitrile was injected before poisoning with CCl4, the liver dysfunction was clearly prevented. The lipid accumulation in the liver produced by CCl4 was partially prevented by the administration of 50 mg/kg of aminoacetonitrile, which also inhibited the elevation of plasma fatty acids induced by the administrations of CCl4 and morphine or by exposing the rats to cold, but not that induced by norepinephrine, etc. The protective effect of aminoacetonitrile on the mobilization of free fatty acids and lipid accumulation procuced by CCl4 was not observed in reserpinized rats. It is concluded from these results that CCl4 increases the mobilization of free fatty acids by stimulating the sympathetic nervous system. Furthermore, it is considered that the effect of aminoacetonitrile on the lipid accumulation induced by CCl4 is due to inhibition of the mobilization of fatty acids.
Effect of aminoacetonitrile (AAN) on hepatic injuries by treatment with carbon tetrachloride was examined in adrenalectomized rats. The liver necrosis produced by CCl4 in adrenalectomized rats was clearly inhibited by AAN. This inhibitory effect of AAN on necrosis was also observed in adrenalectomized rats which were protected from the depression of body temperature by being kept in a warm room. Impaired mobilization of free fatty acids (FFA) marked depression of body temperature, and a little accumulation of liver lipid were observed in adrenalectomized rats by treatment with CCl4. The elevation of plasma FFA and fatty infiltration in the liver were reproduced by the administration of CCl4 when adrenalectomized rats were kept in a warm room or were treated previously with hydrocortisone. Lipid accumulation in the liver of adrenalectomized rats was not inhibited by AAN, but its inhibitory effect on fatty liver was clearly observed in warmed adrenalectomized rats. The mobilization of FFA and the accumulation of liver fat produced by CCl4 in adrenalectomized rats which were previously treated with hydrocortisone were prevented by the injection of AAN or trimethidium. These results indicate that the mobilization of FFA which is observed after the administration of CCl4 is due to the stimulation of sympathetic nervous system, and the released FFA gives marked influence on the development of fatty liver. Furthermore, it is concluded that AAN protects the liver partially from lipid accumulation by inhibiting the mobilization of FFA.
Reaction of 3-cyano-2-methylthio-4H-quinolizin-4-ones (I) with active methylene compounds afforded compounds (II) in which the methylthio group and active methylene were exchanged. Reduction of ethyl 2-amino-3-cyano-4-oxo-4H-quinolizine-1-carboxylates (V) with sodium borohydride was found to produce ethyl 2-amino-3-cyano-4-oxo-1, 6, 7, 8, 9, 10-hexahydro-4H-quinolizine-1-carboxylates (VII).
Reactions of 2-methyl-3-aminoisocarbostyril (I) with several acid anhydrides and acid chlorides were examined using acetic anhydride, acetyl chloride, benzoic anhydride, benzoyl chloride, oxalyl chloride and trans-cinnamoyl chloride. Acylation of C-4 in I, giving II, V, and X, took place predominantly in these cases, although the reaction of I with acryloyl chloride gave VIIa as the main product.
Color reaction of bromophenol blue (H2A) with tertiary amines (B) in non-aqueous solvents was examined and this reaction was compared with that in ethyl acetate. This reaction in benzene, dioxan, and tetrahydrofuran is similar to that in ethyl acetate, but the reaction in methanol, ethanol, and acetone is different. Molecular coefficients and equilibrium constants in the former solvents were determined from equations (1) and (2), and the solvent effect on this reaction was examined. H2A+B⇌BH+·HA- K1=[BH+·HA-]/[H2A]·[B] BH+·HA-+B⇌BH+(BH+·A2-) K2=[BH+(BH+·A2-)]/[BH+·HA]·[B] In this case seven kinds of amines including trimethylamine, triethylamine, and dimethylcyclohexylamine, were used. Examination of the color reaction of sulfonephthalein dyes other than bromophenol blue with tertiary amines in benzene and methanol showed that bromophenol blue, in which the acidity of phenolic hydroxyl was greatly strengthened by bromine in the ortho-position, indicated a high reactivity and was the best dye for reaction with amines.
Examination was made on the substituent effect on the color reaction of bromophenol blue (H2A) with tertiary amines (B) in benzene and ethyl acetate. Eleven kinds of dimethylamine derivatives Me3N-R (R=metyl, ethyl, propyl, iso-propyl, benzyl, etc.) were used and equilibrium constants, ΔH and ΔS in equation (2), were determined. H2A+B⇌BH+·HA- K1=[BH+·HA-]/[H2A]·[B] BH+·HA+B⇌BH+(BH+·A2-) K2=[BH+(BH+·A2-)]/[BH+·HA-]·[B] Comparison of the δRlog K2 (difference of the logarithmic equilibrium constants between trimethylamine and each amine) with Taft's σ* value indicates that δRlog K2 reflects the polar substituent effect to some extent. As may be seen from ΔH-ΔS diagram, the additional steric effect of the methyl group introduced into α-carbon increases the entropy and influences the reaction. This reaction is an enthalpy-entropy controlled reaction.
Transannular reaction of 6-dehydro-17α-methyltestosterone (I) and/or 4, 6-androstadiene-3, 17-dione (V) with hydrogen sulfide, in the presence of sodium methoxide, mainly afforded the corresponding 5α, 7α-disulfide, II and VI, respectively. Selective reduction of VI with sodium borohydride at room temperature below 30° yielded a mixture of 5α, 7α-epidithioandrostane-3α, 17β-diol (VIII) and its 3β isomer (IX). Further treatment of sodium borohydride at 60° converted dioldisulfides (VIII and IX) to diol-dithiols, which were isolated as tetraacetates (XIV and XV, respectively).
A previous work showed that barley β-amylase was inhibited by the addition of isothiocyanates in the enzyme reaction medium. As isothiocyanates were slightly soluble or insoluble in water, previous study was not performed under the condition of the solution competely. Using detergents for the solubilizing isothiocyanates in the present work, the effect of solubilized isothiocyanates on β-amylase was examined. It was found that β-amylase activity was not inhibited by the addition of isothiocyanates which were solubilized by Tween 20 or 80 in the medium.
Sympathetic ganglion blocking actions of 2, 5-diaminotropone (DAT) were investigated and the following results were obtained. 1) In rats and cats, DAT produced a long-lasting fall of the blood pressure. 2) DAT blocked the cat superior cervical ganglion and guinea-pig hypogastric nerve ganglion. 3) DAT potentiated the contraction of cat nictitating membrane induced by electrical stimulation of the superior cervical postganglionic fiber and the contraction of guinea-pig vas deferens induced by electrical stimulation of the hypogastric postganglionic fiber. 4) On rabbit jejunum-mesentery preparation (Finkleman's preparation), DAT did not inhibit the responses induced by the electrical stimulation of postganglionic fiber. 5) DAT showed a weak atropine like action. 6) Sympathetic ganglion blocking activities of DAT were about ten times more potent than hexamethonium, and LD50 (i.v.) of DAT was less than 1/5 of that of hexamethonium.
The chemical components of Japanese Baizhi (Byakushi), the root of Angelica dahurica BENTH. et HOOK. (Umbelliferae), were investigated. As coumarin components, xanthotoxin, marmesin, scopoletin, anhydrobyakangelicin (isobyakangelicol), and neobyakangelicol (I) were newly isolated, in addition to byakangelicol, byakangelicin, phellopterin, oxypeucedanin, and imperatorin reported previously. The structure of I was elucidated as 5-methoxy-8-(2'-hydroxy-3'-methyl-buten-3'-yl) oxypsoralen from the following reasons. 1) Its ultraviolet (UV) spectrum resembles one of byakangelicin. 2) The elementary analysis and the mass spectrum suggest the molecular formula of C17H16O6, corresponding to an isomer of byakangelicol and anhydrobyakangelicin. 3) Its nuclear magnetic resonance (NMR) (Fig. 1) and infrared (IR) spectra show that I possesses a methyl, a hydroxyl, and a vinyl methylene groups. 4) Treatment of I with formic acid produces 5-methoxy-8-hydroxy-psoralen (II). Furthermore, alloisoimperatorin and II were isolated from the distillattion residue of petroleum-ether extract of the root.
The structure of lyofolic acid (I) has been suggested to be a glucoside of a tetracyclic triterpenecarboxylic acid with a cyclopropane ring and an acetyl group on the basis of chemical reactions and physical data of its derivatives. The aglycone, lyofoligenic acid (II) obtained by acid hydrolysis of I, no longer possesses the cyclopropane ring, since the latter was converted into a methyl group and a tetrasubstituted ethylenic linkage during the hydrolysis. On the other hand, protolyofoligenic acid (XIV), having a cyclopropane ring, has been isolated from the extract of the leaves and proved to be the intrinsic aglycone of I.
In order to examine the anti-inflammatory and analgesic activities of indoline derivatives, 3-substituted 1-benzylindolin-2-ones were synthesized. Anti-inflammatory and analgesic actions of 21 of these derivatives were examined by the antiwrithing test in mice and, at the same time, their effect on general behavior and their acute toxicity were also tested. Compounds with strong antiwrithing activity and low toxicity were found in 3-substituted aminomethyl-3-hydroxy compounds.
Various xylitol-iron-citrate complexes were prepared by addition of 0.15 molar ratio of sodium citrate to iron (III) to the xylitol-iron complexes, which were obtained by the static hydrolysis of aqueous solution of ferric chloride hexahydrate with Amberlite IRA-410 (OH type) in the presence of 0-1.42 molar ratio of xylitol to iron (III) (X1/Fe). Particle properties of the xylitol-iron-citrate complexes, plasma iron level, and urinary excretion of iron following intramuscular administration of the complexes were examined. (1) Sedimentation constant of the complexes decreased with augmentation of X1/Fe as follows : X1/Fe=0 : 21.6S, X1/Fe=0.36 : 7.2S, X1/Fe=0.71-1.42 : 4.0-4.7S. (2) There was a tendency for the maximum iron level in plasma and urinary excretion of iron to increase during the first 24 hr after application with decreasing molecular weight of the complexes.
Thiocyanation of 2-alkylamino-(I), 2-N-methylacetamido-(III), 2-imino-(V), 2-acetylimino-(VII), 2-hydroxy-(IX), 2-oxo-(XI), 2-mercapto-(XIII), 2-alkylthio (XV), 2-alkylsulfonyl-(XVII), and 2-thioxothiazoles-(XXIII) was studied. Thiocyanation was carried out by the bromine method using bromine and potassium or ammonium thiocyanate and by the urea method using monochlorourea in place of bromine. The reaction proceeded in the cases of I, III, VIII, IX, XI, and XV, giving 5-thiocyanato derivatives in a good yield, but no thiocyanated product was obtained from the reaction of V, VIII, XVII, and XXIII. Generally the urea method gave better results than the bromine method. 2-Alkylsulfonyl (or 2-arylsulfonyl)-5-thiocyanatothiazoles (XXI) were synthesized by oxidation of the corresponding 2-alkylthio (or 2-arylhio)-5-thiocyanatothiazoles (XVI) with an excess of peracetic acid.
1) By immunizing rabbits with inactivated Vibrio cholerae, the occurence of a factor inhibiting the crisis of cholera, termed cholera crisis-inhibiting factor (CCIF), was recognized in the small intestines of the rabbits. This CCIF could be found only in the small intestine of immunized rabbits, and not in any other organs, or the serum of immunized rabbits, and in the small intestine of non-immunized rabbits. 2) The occurence of CCIF with immunization was clearly distinguished from the formation of an antibody in the blood, the difference in the period of their formation, and by the fact that the serum antibody titer cannot be recognized in the case of CCIF. 3) Two active fractions, S-1 and S-4, were obtained by successive purification, such as by column chromatography on DEAE-cellulose, gel filtration on Sephadex G-100, and column chromatography on carboxymethyl cellulose (CMC), after extracting with Triton X-100, but it did not result in complete purification to obtain a single component. 4) S-1 is a glycoprotein with a molecular weight of about 300000 anb contains immunoglobulins such as IgA and IgG. S-4 is a new protein with a molecular weight of about 300000 and does not contain any immunoglobulins. 5) Further examinations are required to find the essential nature of CCIF, whether the activity of S-1 is related to the local antibody system and whether the activity of S-4 is related to inhibition of the intestinal permeability.
Two components of Aminosidin were isolated in the form of N-acetyl derivatives by cellulose chromatography. The acetyl group of the component was hydrolyzed with hydrazine hydrate to produce an active substance. A major component, Aminosidin I, was identified with Paromomycin I, and a minor component, Aminosidin II with Paromomycin II respectively.
The present work was undertaken in order to synthesize compounds related to bucolome (I) in which an amino and a carboxyl group were substituted in the γ-position of the butyl group in its 5-position. The Bucherer reaction of 5-(3-oxobutyl) barbituric acid derivatives (III and IV) gave the intermediate hydantoin compounds (V and VI) but not the amino acid derivatives from their hydrolysis. The Strecker reaction of III gave 5-(3-amino-3-carboxybutyl)-1-cyclohexylbarbituric acid (VII), with pyrimido [4, 5-b] oxepin derivative (VIII) as a by-product. The Strecker reaction of IV afforded 5-(3-carboxy-3-hydroxybutyl)-1, 3-dicyclohexylbarbituric acid (XIII) and a spirobarbituric acid derivative (XIV).
The Vilsmeier reaction was examined in order to synthesize 5-formylbarbituric acid and 5-formyluracil derivatives. The Vilsmeier reaction of barbituric acid derivatives (I to VI) in excess phosphoryl chloride afforded 6-chloro-5-formylbarbituric acid derivatives (VII to XII), while the same reaction in benzene gave 5-dimethylaminomethylenebarbituric acid derivatives (XIV to XVII) as intermediates whose hydrolysis with alkali afforded 5-formylbarbituric acids (XVIII and XIX). The Vilsmeier reaction of 1, 3-disubstituted uracil derivatives (XV to XVIII) produced 1, 3-disubstituted 5-formyluracil deivatives (XXIX to XXXII).
Guaiazulene formed blue needle crystals on reaction with maleic anhydride or acrylic acid in a boiling water bath. The products obtained in this experiment were confirmed as 3-(7-isopropyl-1, 4-dimethyl) azulenyl compounds from visible, infrared, nuclear magnetic resonance, and mass spectra, and maleic anhydride adduct was found to be dissociated at a high temperature from gas chromatography and mass spectra.
The actions of 1-phenyl-4-guanylpiperazine sulfate (PGP), which has the property of monoamine oxidase inhibitor and of Nialamide on the concentration of norepinephrine (NE) in the brain and heart of rats were investigated. PGP increased the NE concentration by about 34.5% in the brain and 42.7% in the heart, and Nialamide also increased it by about 33.7% in the brain and 76.3% in the heart 24 hours after the intraperitoneal administration of 100 mg/kg. These percentage were significant (p<0.05).
The steam-volatile constituents of air-dried bud of Eugenia caryophyllata THUMBEDG were examined by gas chromatography, and from infrared, nuclear magnetic resonance, and mass spectra. Eugenol (I) 80.87%, β-caryophyllene (II) 9.12%, acetyleugenol (III) 7.33%, and nine other minor components were identified. Besides the previously reported components (I, II, III, methyl amyl ketone, methyl salicylate, α- and β-humulene), benzaldehyde, benzyl alcohol, benzyl acetate, m-methoxybenzaldehyde, α-ylangene, and chavicol were newly detected.
An improved method for the spectrophotometric determination of Sn (IV) with gallein was devised. Considerable reduction in time was achieved by the addition of oxalic acid and cetylpyridinium chloride. A spectrophotometric determination of oxalic acid was also established. A recommended procedure is as follows : To the solution of Sn (IV) are added 1.5 ml of 1.0×10-2M cetylpyridinium chloride solution, 0.3 ml of 1.0×10-3M C2O42- solution, and 1.0 ml of 1.0×10-3M methanolic gellein solution. To another solution of C2O42- are added 1.5 ml of 1.0×10-2M cetylpyridinium chloride solution, 0.5 ml of 5.0×10-4M Sn (IV) solution, and 0.2 ml of 1.0×10-3M methanolic gallein solution. A mixture of these two solutions is diluted to 10 ml with water and 3% sulfuric acid. The absorbance is measured at 530 nm for Sn (IX) and C2O42- after standing for 15 minutes at 25°.