Works on the total syntheses of the following Amaryllidaceae alkaloids are described : haemanthamine, haemanthidine, pretazettine, tazettine, crinamine, 6-hydroxycrinamine, criwelline, macronine, lycorine, dihydrolycorine, zephyranthine, ungiminorine, and dihydrolycoricidine.
The synthetic method of 3-ureido-2-pyrazolin-5-ones by use of 3-phenoxycarbonylamino-2-pyrazolin-5-ones and amines was developed. This method is superior to that by using 3-amino-2-pyrazolin-5-ones and isocyanates with respect to the following facts. 1) This method is not influenced by the presence of moisture. 2) Starting materials of this method are considerably stable in storage. 3) Not only 3-N'-mono-substituted ureido-2-pyrazolin-5-ones but also 3-N', N'-di-substituted ureido derivatives are obtained by this method. 4) Without protecting group, substituents having hydroxy or amino group are introduced into 3-ureido-2-pyrazolin-5-ones by this method. 3-Ureidoanilino-2-pyrazolin-5-ones are also synthesized from 3-phenoxycarbonylaminoanilino-2-pyrazolin-5-ones and amines.
Oxidation of hydrazone derivatives of pyridine-2-carbaldehydes (XIII, XIV a) and 2-pyridyl ketones (XIV b-h) with nickel peroxide (Ni-PO) in benzene at room temperature afforded [1, 2, 3]-triazolo [1, 5-α]-pyridines (IV, XV a-h) in good yields. The starting substituted phenyl 2-pyridyl ketones (VIII a-d) were obtained by Ni-PO oxidation of the corresponding alcohols in good yields. When the substituent was p-NO2 or m-NO2 on phenyl group, the Ni-PO oxidation could not afford the ketones but the starting alcohols were recovered. The oxidation of 5-ethyl-2-hydroxymethylpyridine (IX) with Ni-PO did not give the aldehyde but nickel complex (X) was obtained. The reaction mechanisms of Ni-PO and hydrazones are discussed.
It was found that 3-(4-methoxyphenyl)-4-oxazolidinone (IIa) had analgesic activity as potent as aminopyrine and very low toxicity. In order to obtain more excellent analgesics, 3-(substituted phenyl)-4-oxazolidinones (1-10) related to (IIa) and 3-(substituted phenyl)-3, 4, 5, 6-tetrahydro-2H-1, 3-oxazin-4-ones (11-30) were prepared and examined for the analgesic activity. Among the active compounds, 3, 4, 5, 6-tetrahydro-3-(4-methylphenyl)-2H-1, 3-oxazin-4-one (20) showed the strongest activity (ED50=29mg/kg).
The precipitation of ternary complex of chrome-azurol S, Al3+ and quarternary ammonium ions was avoided by using polyethylene glycol-p-nonylphenyl ether n=10, and the stable solution was submitted to a spectrophotometric determination of quarternary ammonium ions. In the case of cetyltrimethylammonium bromide, the absorbance at 615 nm against reagent blank obeys Beer's law over the range between 5.0 and 50.0μg in a final volume of 15 ml, the ε value and coefficient of variation being 7.86×104 and 1.76%, respectively. This simple and highly sensitive method was applied to benzalkonium chloride and benzethonium chloride etc., although a few ions such as Fe3+ interfere the determination.
In order to investigate the antibacterial activity of α-acylpentapeptide, acyl-Lys-Lys-Thr-Lys-D-Leu-OH was synthesized by the acylation of pentapeptide obtained by the condensation of tripeptide and dipeptide with dicyclohexylcarbodiimide. It was proved that α-acylpentapeptide has stronger antibacterial activities against gram-negative bacteria than the corresponding non-acylated pentapeptide.
The effect of oral hypoglycemic agents on gastric secretion was studied in alloxan diabetic rabbits. Peptic activity was measured with bovine haemoglobin as substrate, as reported in the Committee to Discuss the Determination of Gastric Juice in the Gastroenterological Society of Japan. Gastric acidity was estimated by Topfer-Michaelis' method. Blood sugar was determined by using Glucose B-Test, while amylase activity in blood was determined by use of Amylase Test. Buformin hydrochloride, glymidine sodium and glyclopyramide were used as a hypoglycemic agent. Gastric secretion volume, gastric peptic activity, pepsin and acid output reached the maximum at 3-4 hours after the administration of hypoglycemic agents, which was related to blood sugar level. Free and total gastric acidity and amylase activity in blood were not significantly affected. Among the effects of these three drugs on the peptic activity, pepsin output, and blood sugar level after their respective oral administration, we could find some significant differences.
The interactions of phenytoin (DPH) with α-, β-, and γ-cyclodextrins (CyD) in aqueous solution were investigated by solubility analysis, ultraviolet absorption and circular dichroism spectroscopies. The apparent stability constant of β-CyD-DPH complex was found to be the largest among the three CyD complexes. The solid complexes of β-CyD with DPH in molar ratio 1 : 1 were prepared by a variety of methods (freeze drying, kneading, solvent evaporation, and coprecipitation), and the interaction between host and guest molecules was confirmed by infrared and X-ray diffraction measurements. The pharmaceutical characteristics of the solid complexes such as dissolution, permeation through a cellophane membrane, particle size, and in vivo extent of bioavailability were examined in comparison with those of DPH alone. The complex obtained by the freeze drying method showed the smallest particle size with the highest dissolution rate and membrane permeability among the test powders. The complex increased significantly the levels of plasma concentration of DPH after oral administration to dogs. The increase of bioavailability of DPH by means of β-CyD complexation suggested the possibility of smaller doses and fewer side effects in DPH therapy.
To clarify the diffusional behaviors of benzocaine in the presence of macrogol 400 (PEG), viscosity, solubility and cellulose membrane permeation rate of benzocaine were determined with PEG solutions of various concentrations. With an increase in PEG concentration, permeation rates of benzocaine from solutions (benzocaine conc. <solubility) decreased due to an increase in viscosity of the solution. From suspensions (benzocaine conc. >solubility), however, permeation rates increased due to an increase in benzocaine solubility.
A method of quantitative determination of curcumin in Curcuma longa was established by using high performance liquid chromatography. Curcumin contents of methanol, aqueous methanol-(4 : 6) and water-extracts of turmeric (rhizomes of Curcuma longa L.) were determined by high performance liquid chromatography (HPLC) by use of Nucleosil C18 column as a stationary phase, a mixture of CH3CN : H2O : CH3COOH (51 : 49 : 5) as a mobile phase and benzyl benzoate as an internal standard. The present method is preferable to other analytical methods with regard to accuracy, simplicity and speed.
A high performance liquid chromatographic method for the determination of trace amounts of formaldehyde in commercial clothing as its lutidine derivative is described. By elution with hexane/ethanol (25 : 1 v/v) on a silicagel treated with 20% (3-aminopropyl) triethoxysilane and a Nucleosil 5 NH2, the resolution peaks with formaldehyde and acetaldehyde (i.s.) were 4.25 and 1.72, respectively. By this method, the amount of formaldehyde was determined within 1.83% error in the range 0.02-1.0μg and 0.05-6.0μg in 1 ml of aqueous solution by using a fluoresence spectrophotometer and a visible spectrophotometer, respectively, and the limit of detection was 100 pg.