A method was devised to prepare the amino acid-iron (II) chelate by a simple electrolysis using amino acid suspended in water as the electrolytic solution and passing a current of ca. 0.07-0.17A./cm2 between iron anode and cathode. In order to study the specific behavior and properties of amino acids during this electrolysis, iron (II) chelates of L-and DL-aspartic acids were examined. It was assumed that L-aspartic acid was coordinated as a ligand with coordination number of three but that DL-aspartic acid was a ligand with coordination number of two.
Oxidation of cholesterol in acetone was investigated with the use of the Kiliani reagent at 0° and Cholest-4-ene-3, 6-dione (IV) was prepared in 72% yield with excess reagent. 2, 4-Dinitrophenylhydrazones and p-nitrophenylhydrazones of these ketosteroids (II, III, IV) were prepared, purified, and characterized by the determination of their elemental compositions, melting point, and visible absorptions. Cholest-4-ene-3, 6-dione mono (p-nitrophenylhydrazone) (X) in dimethylformamide shows an absorption maximum at 612mμ in sodium hydroxide solution and has an apparent molecular extinction coefficient of about 64, 400. The present work suggested a possibility to develop a novel method for the determination of cholesterol.
A number of piperidinoalkyl derivatives were prepared and their acute toxicity, potentiation of methylhexabital narcosis, and protection against electroshock convulsion were examined to clarify the relationship between chemical structure and central nervous system deppressant effect of 2-piperidinomethyl-1-tetralone analogs. Among the compounds tested, 2-piperidinomethyl-3-methyl-1-tetralone (III) possessed an activity comparable to that of 2-piperidinomethyl-1-tetralone (I), but others had lesser activities.
A new method for synthesis of 2-indanamine (I) was found to give I in a comparatively good yield by derivation. As a new method for the synthesis of 2-indanamine, 2-nitroindene (V) was found to be obtained in a comparatively good yield by acetylation of indene nitrosite (II) to 1-acetoxy-2-nitroindane (IV) and its hydrolysis. Examination was made on the method reported by Denstedt and others, and it was assumed that the β-compound of indene nitrosite reported by him might be 2-nitro-1-indanone oxime (III).
2-Indanamine (I) has a strong analgesic action and its various derivatives were synthesized to examine their activity. However, none of the derivatives synthesized, N-(3-dimethylaminopropyl)-2-indanamine (II) and its acetylated compound (III), N-(2-dimethylaminoethyl)- (IV) and N-(2-anilinoethyl)-2-indanamine (VI), and bis (2-indanyl)-amine (VII), showed any better analgesic action than I.
In order to test the analgesic action of 3, 4, 5, 6-tetrahydro-2H-1, 5-methanobenzo[e]-[1, 4]diazocin (XXI), methods for its synthesis was examined using various starting materials. Compounds (XI to XIII) were synthesized from 3-bromoquinoline (V). Their derivation to XIV or synthesis of XXI by reduction of V was tried but the objective was not attained. Finally, V was derived to XXI by amination, benzoylation, N-alkylation by ethyl chloroacetate, and reduction to the lactam (XX), and its reduction with lithium aluminum hydride (method d). XXI was also obtained from XV by the route shown in Chart 2.
Michael condensation of 1 mole of 6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinolineacetonitrile (III) and 2 moles of acrylonitrile by heating in a sealed tube at 110° for 6 hours afforded a small amount of condensate (VII) of nitrite (III) with 1 mole of acrylonitrile besides γ-cyano-γ-(2-cyanoethyl)-6, 7-dimethoxy-3, 4-dihydro-1-isoquinolinebutyronitrile (VI). Cyclization of this condensate (VII) by refluxing with sodium ethoxide for 30 minutes gave the amidine (VIII). Hydrolysis of this amidine to the lactam (IX), its derivation to thiolactam (X) by the usual method, and desulfurization reaction with Raney nickel afforded XI. Catalytic reduction of XI over platinum dioxide in the presence of hydrochloric acid unexpectedly caused the liberation of nitrile to form 9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-11bH-benzo[a]quinolizine (XII), whose infrared absorption spectrum agreed completely with that of the authentic specimen synthesized by another route.
Nitration of furil and furoin with a mixed acid of acetic anhydride, fuming nitric acid, and a small amount of conc. sulfuric acid at -10° to -15° afforded 5, 5′-dinitrofuril from the former and 5-nitrofuril from the latter. Nitration of 2, 3-difuryiquinoxaline, obtained by condensation of furil and o-phenylenediamine, with acetic anhydride and fuming nitric acid gave 2, 3-bis(5-nitro-2-furyl)quinoxaline in a good yield of 70%. The same nitrated product was obtained from the condensation of 5, 5′-dinitrofuril and o-phenylenediamine. Oxidation of 2, 3-difurylquinoxaline and 2, 3-bis(5-nitro-2-furyl)quinoxaline with potassium permanganate afforded 2, 3-quinoxalinedicarboxylic acid, which was identified by synthesis through another route and through infrared spectrum.
Aminoethylguanidine derivatives, unknown 1-[2-(N, N-diphenylamino)ethyl]guanidine sulfate (I) and 1-[2-(N-methyl-N-phenylamino)ethyl]guanidine sulfate (II), and known 1-[2-(N, N-diethylamino)ethyl]guanidine sulfate (III), 1-[2-(N, N-dipropylamino)ethyl]guanidine sulfate (IV), 1-[2-(N, N-diisopropylamino)ethyl]guanidine sulfate (V), and 1-(2-piperidinoethyl)guanidine sulfate (VI) were synthesized. Effects of these compounds on blood pressure of albino rats and rabbits, pharmacological actions in general, and acute toxicities were comparatively examined with guanethidine and its derivative, 1-[2-(hexahydro-1-azepinyl)ethyl]guanidine sulfate (VII). III and VI have hypotensive action of fairly long duration on rats and rabbits but their activities were less than that of guanethidine. VII showed long-lasting depression of blood pressure in rabbits but temporary depression in rats. In these compounds, 1-[2-(N, N-diphenylamino)ethyl]guanidine sulfate (I) showed a marked muscle relaxation on N. ischiadicussartorius preparation of Rana nigromaculata. Its activity was almost the same as that of succinylcholine chloride. Antispasmodic and antihistamine activities were tested with isolated small intestine of mice and guinea pigs, respectively. Acute toxicities in mice were also tested. The structure-activity relationship is briefly discussed.
High-molecular derivatives of thiamine with disulfide-linkage were prepared by the thiol-disulfide exchange reaction between thiamine disulfide and homopolymers of N-acryloylcysteine, N-methacryloylcysteine or copolymers of other vinyl compounds. Examinations were made on the same reaction with other polyvinylthiols and starch dimercaptoallyl ethers but the objective disulfide compounds were not obtained. Stability of these disulfide-type high-molecular thiamine derivatives was examined by mixing with sodium hydrogen carbonate-starch (1:1) and calcium carbonate and it was found that they were markedly more stable than thiamine hydrochloride and were very stable when suspended in buffer solutions of various pH and heated. Determination of thiamine excreted in human urine after their oral administration showed that the amount was equal to or greater than that of thiamine hydrochloride, both in the case of homopolymers and copolymers. Urinary excretion was almost doubled in the poly (N-acryloylcysteine) derivative. Urinary excretion extended over a long period, showing the specific action of the polymer derivatives.
2-Chloropyridine 1-oxide forms 2-aminopyridine 1-oxide and 3-aminopyridine 1-oxide, though in a low yield, by treatment with liquid ammonia in the presence of potassium amide. Under the same conditions, 3- and 4-chloropyridine 1-oxides give only 3- and 4-amino compounds, respectively. It follows, therefore, that the mechanism of these reactions is entirely reverse of that of chloropyridine reported by Hertog; that of the 2-chloro compound being a benzyne mechanism and that of 3- and 4-chloro compounds being amination by SN-2 mechanism.
In order to study the precipitation conditions of soluble proteins in bovine lens cortex, precipitation titration with the aid of light scattering apparatus was examined by the use of acetic acid, hydrochloric acid, acetone, and ammonium sulfate as a precipitant to be added continuously to the protein solution in the cell at 5° and 34°. Transmitted light in the direction of 0°, and scattered light in the direction of 45°, 90°, and 135° were recorded. At directions of 0°, 90° and 135°, the number of maximum point in the precipitation titration curve was one. The scattered light at the direction of 45°, on the contrary, had two maximum points, for each precipitant and temperature. It was also found that the first maximum was located at pH 5.5 and the second at pH 4.5. The minimum point between the first and the second was observed at pH 5.0, the value corresponding to the maximum point in the direction of 90° and 135°.
The volume fractions of each component in the dilute phase (υ1′, υ2′, υ3′) and in the concentrated phase (υ1″, υ2″, υ3″) were calculated according to Flory's and Scott's theoretical equations, in the ternary system of solvent-1, nonsolvent-2, and polymer-3. These values at the plait point were also calculated, (υ1)pl, (υ2)pl, (υ3)pl. In these treatments it was assumed that P1=P2=1, P3>>1 for the polymerization degree Pi; and A=0, B=0, C≠0 for the interaction parameters. From these calculations, relation between the initial concentration of polymer (υ3)° and the swelling ratio of the precipitated polymer 1/υ3″ were calculated as functions of the relative volume of nonsolvent added to the system (V/V0). Relation between the relative volume of nonsolvent added to the system (V/V0)pl before the precipitation starts and the polymerization degree P were also calculated for various values of parameter C. From these results it became evident that the fractionation effect will be good when the dilute polymer solution and nonsolvent of small interaction parameter C are used. Theoretical solubility limit equation was obtained of polymers of various polymerization degree.
Monotropein, C16H22O11⋅CH3OH, was isolated from the domestic Monotropa Hypopithys L. (Japanese name “Shakujoso”) and it was proved to be identical with the corresponding glucoside isolated from the other plants belonging to the genuses of Pyrola and Chimaphila. In view of the fact that monotropein was also isolated from the other pyrolaceous saprophytes, Monotropa uniflora L. (Japanese name “Ginryoso-modoki”) and Monotropastrum globosum H. ANDR. (Japanese name “Ginryoso”), this glucoside is considered to be common to the pyrolaceous plants. In these three kinds of plants, a few sugars like glucose and sucrose, and some Gibbs' reaction-positive substances, assumed to be hydroquinone-type glucosides were detected by paper chromatography.
During examination of antimicotic substance, a crystalline substance with strong sublimability, having a characteristic odor, was isolated unexpectedly from the culture broth of a kind of Bacillus subtilis and its chemical structure was examined. Properties of this substance and its derivatives, their infrared absorption spectra, and analytical values suggested the substance to be a tetramethylpyrazine and the fact was confirmed by comparison with tetramethylpyrazine synthesized by the known method.
In continuation of the work carried out by T. Takahashi in 1938 on a crystalline constituent of the bark of Abies mariesii MAST. (Pinaceae), extensive investigations of this compound, now named abieslactone, were undertaken. Selenium dehydrogenation of abieslactone, C31H48O3, gave four crystalline hydrocarbons including a homolog of naphthalene, 1, 2, 8-trimethylphenanthrene, a homolog of chrysene, and an alkylnaphtho [2, 1-a] fluorene. These findings indicated that abieslactone possibly possesses the skeleton of trimethylsteroid.
10-Isopropyl-1, 7-dimethyl-11H-naphtho[2, 1-a]fluorene was synthesized by the sequence of reactions shown in Charts 1, 2, and 3. The compound thus obtained was not identical with the hydrocarbon m.p.199-200° obtained by the selenium dehydrogenation of abieslactone, a triterpenoid occurring in Abies mariessi.
Absorption spectra in the visible range were examined in iron (III) complex salts of hydroxamic acid of various higher fatty acids listed in Table I and they were all found to show behavior exactly the same as that of myristohydroxamic acid reported in the preceding paper.*2 All the hydroxamic acids were found to form complex salts in the ratio of 1:1 (λmax 525mμ) at pH 2.0, of 2:1 (λmax 495mμ) and of 3:1 (λmax 485mμ) at pH 5.0. A method was devised for colorimetric determination of hydroxamic acids of higher fatty acids by using the 1:1 complex salts formed at pH 2.0.
Condensation of ammonium phenyldithiocarbamate with aliphatic amine hydrochloride in ethanol and cyclization of the product by dropwise addition of 37% formaldehyde under stirring afforded 10 kinds of 2-thio-1, 3, 5-tetrahydrothiadiazine derivatives. In vitro biological tests of these compounds showed that they had only a weak antibacterial activity but some of them had a strong antifungal activity.
The thin-layer chromatograghic behavior of bisflavones and their derivatives was examined for characterisation of extracts obtained from the leaves of gymnosperms. Results of chromatography suggested the possible presence of bisflavones other than those reported.
Two bitter principles (A and B) were isolated from the leaves of Clerodendron trichotomum THUNB. A: C24H34O9 or C26H36O10, needles of m.p. 152-155°(decomp.), [α]D+5.6°. B: C23H32O9 or C25H34O10, prisms of m.p. 232-235°, [α]D-71.5°. Both are different from clerodin and its related compounds, but should be similar to them.
The keto acid, C30H58O3, m. p. 99-101°, isolated from the seeds of Papaver somniferum L. was identified as 11-oxotriacontanoic acid by a chemical method and measurement of infared, nuclear magnetic resonance, and mass spectra.
Sanguisorbigenin (I), a triterpene obtained from the roots of Sanguisorba officinalis L., was found to have the same structure as that of tomentosolic acid (19-dehydroursolic acid) from their physical and chemical properties.
From the ether extract of the fruits of Paederia chinensis HANCE, 1.5% oleanolic acid, triacontane, and hydroquinone were separated. Acetic acid, propionic acid, unsaturated fatty acid, phenol, butyraldehyde, and terpenealdehyde were isolated from the distillate of steam distillation of the plant. Arubutine was found from the hot-water extract of the plant. The amount of arubutine in the fruits is proved to be 0.69, and 0.86% in the dried leaves. Neutral oil has a unique odor of this plant and the odor disappears when the oil is treated with potassium hydroxide solution.