Strain in a molecule sometime plays an important role on the reactivity of the molecule. We present stereospecific reactions of strained polycyclic cage compounds, unusual reactivity of constrained cage ketones and their applications for the syntheses of some novel ring systems.
The reaction conditions for the one-step synthesis of purine by heating formamide were investigated. Purine was formed as a main product when formamide was heated at 175-185° in a sealed vessel ; reaction temperatures above 190° and prolonged heating resulted in decreased purine yields. Purine was not produced when the reaction was performed below 160°, but the introduction of hydrogen cyanide to the reaction vessel gave purine along with adenine, a major product. This indicates that hydrogen cyanide is an essential key intermediate in purine ring formation. A reaction mechanism for purine formation is also proposed.
Solid complex formation of theophylline with ethylenediamine analogues, namely, 1, 4-butanediamine, 1, 5-pentanediamine, 1, 6-hexanediamine, 1, 7-heptanediamine, and 1, 8-octanediamine was attempted from an aqueous and an absolute ethyl alcohol solution. Theophylline forms solid complexes with diamines except 1, 5-pentanediamine and 1, 7-heptanediamine from absolute ethyl alcohol solution, and if forms solid complexes with every diamine from an aqueous solution, in molar ratios of 2 : 1. The solid complexes of 1, 5-pentanediamine and 1, 7-heptanediamine contain two and one molecule of crystal water, respectively. Since these crystal waters combine to the solid complexes weaker than those of aminophylline and the complex of 1, 3-propanediamine, it can be presumed that the solid complexes of 1, 5-pentanediamine and 1, 7-heptanediamine are not formed from absolute ethyl alcohol solution. To study the thermal decomposition of the complexes, differential thermogravimetric analysis was carried out in air, at a temperature elevation rate of 2.5°/min. It showed that the solid complexes having no crystal water, eliminate each diamine accompanied with each endothermic peak in certain temperature ranges and that the solid complexes having crystal water, first lose each crystal water to anhydrous solid complexes in certain temperature ranges and then eliminate each diamine. By applying the equation proposed by Freeman and Carrol, the activation energies of the eliminations of diamines of the complexes of 1, 4-butanediamine, 1, 5-pentanediamine, 1, 6-hexanediamine and 1, 8-octanediamine were calculated as 95.8, 59.0, 66.1, and 71.8 kJ/mol, respectively, and orders of reaction of these, calculated to zero without exception.
The inhibitory substances of the gelation reaction of limulus lysate were purified from human plasma by a five-step procedure. Two purified fractions, E-1 and E-3, were obtained and the recovery of the inhibitory activities in E-1 and E-3 was 8% and 2%, respectively. When examined with disc gel electrophoresis and immunoelectrophoresis against anti-human plasma antiserum, E-3 was revealed to migrate as a single component corresponding to α2-globulin, whereas E-1 migrated as a major component corresponding to α1-globulin and minor components. The major electrophoretic component of E-1 was found to represent 83% of the protein by gel scanning. The major component of E-1 gave a precipitin line against anti-human α1-antitrypsin antiserum, and E-3 against anti-human antithrombin III antiserum by Ouchterlony immunodiffusion and immunoelectrophoresis. The results of molecular weight, carbohydrate, and amino acid analyses of E-1 and E-3 were similar to those of α1-antitrypsin and antithrombin III, respectively. Purified α1-antitrypsin and antithrombin III were also recognized to inhibit the gelation reaction of limulus lysate. These results soggest that the inhibitory substances of the gelation reaction of limulus lysate in human plasma are α1-antitrypsin and antithrombin III and that most of the inhibitory activity is attributable to α1-antitrypsin.
In order to confirm the structure of two urinary metabolites, M-I and M-II, of a new analgesic, (-)-1, 4-dimethyl-10-hydroxy-2, 3, 4, 5, 6, 7-hexahydro-1, 6-methano-1H-4-benzazonine hydrobromide (l-ST-2121), in rats, compounds (-)-1, 4-dimethyl-9, 10-dihydroxy-2, 3, 4, 5, 6, 7-hexahydro-1, 6-methano-1H-4-benzazonine (I), (-)-1, 4-dimethyl-10, 11-dihydroxy-2, 3, 4, 5, 6, 7-hexahydro-1, 6-methano-1H-4-benzazonine (II) and (-)-1-methyl-10-hydroxy-2, 3, 4, 5, 6, 7-hexahydro-1, 6-methano-1H-4-benzazonine (III) were synthesized. Compounds I and III were identified with the urinary metabolites M-I and M-II, respectively. The analgesic activities and acute toxicities of I and III were examined.
Systematic synthesis of S-substituted 6-amino-5-nitroso-2-thiouracils (I-XIII) was performed for the utilization of pyrimidine derivatives as analytical reagents for some metal ions. These thiouracils were found to react easily with iron (II) and cobalt (II) to yield blue and yellow complexes, respectively, which could be extracted with chloroform. The absorption spectra of the complexes in chloroform indicated that III, IV, VI, VII, IX, and XII were potential analytical reagents for iron (II) and cobalt (II). The variation of the alkyl group on the thioxy group exerted no remarkable effect on complex formation. The cobalt (III) complexes of 6-amino-2-benzylthio-5-nitroso-4-oxo-3, 4-dihydropyrimidine (ABNP), 6-amino-2-benzylthio-5-nitroso-4-oxo-1-phenyl-1, 4-dihydropyrimidine (ABNPP), and 1-nitroso-2-naphthylamine (NNA) were prepared to clarify the structures. The formulas of the isolated complexes are Co (III)·(C11H9N4O2S)3·H2O, Co (III)·(C17H13-N4O2S)3·2H2O, and Co (III)·(C10H7N2O)3, respectively. On the basis of UV, IR, NMR, and magnetic susceptibility measurements, the structures for these compounds were proposed. It may be considered that ABNP, ABNPP, and NNA are coordinated to cobalt (III) through the amino and nitroso group.
To deal with missing data in clinical tests, three methods (A, B, and E) were considered. Drug efficacy was estimated by (A) using only actual data, (B) using a previous value for a missing datum, and (E) using the value estimated by the equation (1) for a missing datum. [numerical formula] where S is the symptomatic severity (S0 is at the beginning), b is the recovery rate constant, θ is the number of days after the initiation of medical treatment, and subscript i means the i-th judgment. Based on theoretical calculations and analyses of nine sets of real data in ophthalmology, orthopedics and dermatology, (i) drug efficacy estimated by B was always smaller than by E, (ii) the difference in estimated drug efficacy between A and E was very small.
The completely proton-decoupled 13C-nuclear magnetic resonance spectrum of the 1, 6-anhydro derivative of O-β-D-galactopyranosyl-(1→3)-O-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→3)-O-β-D-galactopyranosyl-(1→4)-D-glucopyranose (lacto-N-tetraose) (8) was measured in D2O. The signals were assigned by direct comparison of the spectra with those of 1, 6-anhydro-β-lactose (lactosan) (5) and O-β-D-galactopyranosyl-(1→3)-O-2-acetamido-2-deoxy-β-D-glucopyranose (lacto-N-biose I) (7), and also by examination of the selectively proton-decoupled, and the partially relaxed Fourier transform (PRFT) spectra. The effect of the glycosylation shift was discussed, and the shift values calculated served for the confirmation of the structure of 8.
From Pieris japonica a new diterpene (asebotoxin-X), a new diterpene glucoside (pieroside A) and hyperin (quercetin 3-O-galactoside) were isolated. The structures of these new natural compounds were determined by chemical and spectroscopic means and by correlation with known compounds.
The hypocholesterolemic activities of phytosterols and related compounds were compared in rats receiving a 3%-cholesterol containing diet. The rats were intravenously injected for 5 days with emulsions of saline-albumin containing each sterol. The greatest effect on lowering liver cholesterol, triglyceride and fatty acids-levels was shown by stigmasterol, followed by β-sitosterol, stigmastanol, ergosterol and 7-ketocholesterol. On the other hand, esters of stigmasterol, such as palmitate and stearate showed considerably lower activity than free stigmasterol. No effect could be seen in stigmasterol acetate, which is not found in nature. Also, the decrease of liver cholesterol by treatment with phytosterols depended on its esterified form. After injection, stigmasterol in liver was present mainly in a free form and the palmitate or the stearate changed partly to the free form, 20% or 25% of the injected amount, respectively. However, stigmasterol acetate remained unchanged after injection. Cytochrome P-450 content of hepatic microsome from hypercholesterolemic rats was significantly decreased by treatment with stigmasterol, and similar findings were obtained in microsomes from livers of normal or phenobarbital-treated rats which had been given stigmasterol. The results suggest that the presence of a free hydroxy group at the C-3 position in phytosterols is necessary for the hypocholesterolemic activities and a double bond at the C-5 position and a side-chain at the C-17 position, may also relate to these activities.
Determination procedures for thiobarbituric acid (TBA) reactive compounds in animal tissue homogenates were studied with sodium dodecylsulphate (SDS) as a tissue solubilizing agent. The treatment of tissue homogenate with SDS increased the TBA value, significantly, particularly, the addition of 2.5-fold SDS to protein concentration in homogenate showed maximum increase of the TBA value upon 30-min heating. The TBA increase, however, was not at a constant rate in all tissues. On the other hand, the effect of SDS was not as great in young rat tissue homogenate accelerated lipid peroxidation with the treatment of ascorbate-FeCl2 or ascorbate-ADP mixture. These observations suggest that the differences in the efficiency of SDS on TBA depend on the physiological membrane conditions. These results suggest that the SDS tissue-solubilizing method is useful for the exact determination of TBA in animal tissues.
A mixture of lactose powders and small-sized lactose granules (32-80 mesh) was shaken in a cylindrical metal vessel and the degree of mixing was examined. The miscibility of the micronized powder with small-sized granules was good. The micronized powder contained as much as 27.8% small particles with diameters less than 10 μm, and it is thought that its cohesive and adhesive property brought about such an improvement in the degree of mixing. The eosine-coated powder exhibited a low degree of mixing, possibly because the adhesive force of these powder particles to the surface of lactose granules, as measured by a modified centrifugal method, was small (0.021 dyn), and cohesion among the particles was large (0.214 dyn). The eosine-coated powder and the powder containing 1% talc were rather free-flowing. However, no improvement on the degree of mixing was obtained by the increase in flowability of the powders.
3', 4' (or 3', 5')-Dichloro-ω-(3-methylpiperidino) acetamidodiphenyl ether (1a, b) was obtained by reduction of the corresponding nitrophenyl ether derivative with stannous chloride and concentrated hydrochloric acid, followed by reactions with chloroacetyl chloride and 3-methylpiperidine. 3'-Chloro-β-(3-methylpiperidino) propionamidodiphenyl ether (2) was obtained by reactions of the corresponding aminodiphenyl derivative with β-bromopropionyl chloride, next with 3-methylpiperidine. 4'-Chloro-ω-(piperidino) acetamidodiphenyl ether (11) and 2 were reacted with methyl iodide to give their corresponding quaternary salts (3-4). ω-(4-Ethoxycarbonyl-4-phenylpiperidino) acetanilide derivatives (5a-w) and ω-(4-hydroxy-4-phenylpiperidino) acetanilide derivatives (6a-w) were obtained by reactions of the corresponding ω-chloroacetanilide derivatives with 4-ethoxycarbonyl-4-phenylpiperidine and 4-hydroxy-4-phenylpiperidine, respectively. The investigation of the effects of the derivatives 1a-b and 3-4 on the intestinal smooth muscle showed that the quaternary salt 3, more weak than 11, competes with acetylcholine. The analgetic action and the action on central nervous system of derivatives 5a-w and 6a-w were both weak.
The reaction of isoquinoline with diketene in benzene at reflux affords 13, 13a-dihydro-11-methyl-8H, 9H-8, 9-dioxobenzo [α] pyrano [3, 2-α] quinolizine (2a) in a 40% yield. When the reaction is carried out at room temperature, compound 2a and 13, 13a-dihydro-9-methyl-8H, 11H-8, 11-dioxobenzo [α] pyrano [3, 2-g] quinolizine (3) are obtained in 3% and 30% yields, respectively. Compound 3 is oxidized with 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) to give 9-methyl-8H, 11H-8, 11-dioxobenzo [α] pyrano [3, 2-g] quinolizine (4) in an 85% yield.
Alkaloids in the cultured cells of Duboisia leichhardtii F. MUELL (Solanaceae) were examined. Nicotine and isobutyloyltropine were determined as authentic samples by the GLC method, and valeroyltropine was estimated by the GC-MS method. However, hyoscyamine and scopolamine, the main alkaloids in Duboisia leaves, were not detected.
A rapid and simple method was developed for the determination of ethylenediamine in aminophylline using high performance liquid chromatography. The method involves reaction of ethylenediamine with ethanolic 9, 10-phenanthraquinone to form stable dibenzo [f, h] quinoxaline derivatives, followed by reversed-phase liquid chromatography with ultraviolet (254 nm) detection. The established method was applied to the photo-stability test of aminophylline preparations and the discoloration was closely related to the degradation of ethylenediamine in the aminophylline preparations.
Several commercial preparations of sodium copper chlorophyllin (Cu-Chl-Na) containing copper chelate compounds of chlorophyll derivatives were examined for their lipid peroxidation inhibitory activities in rat liver homogenates. The inhibitory effect on lipid peroxidation stimulated by both Fe2+ and ascorbic acid differed from preparation to preparation. The potency of the antioxidative activity was found to be correlated with the intensity of the absorption maximum at ca. 628 nm, which was assumed to be attributable to the chemical structure of the copper complexes of chlorin derivatives. On the other hand, the sample which did not show any absorption in the red-band region exerted no effect on lipid peroxidation. These results suggest that the Cu-Chl-Na preparation, which contains a larger amount of copper complexes of chlorin derivatives, has more potent antioxidant activity. In addition, sodium iron chlorophyllin also showed inhibitory action on lipid peroxidation in rat liver homogenates, indicating that the antioxidative effect is not specific for Cu-Chl-Na.