Showing papers in "Chemical & Pharmaceutical Bulletin in 1961"

Studies on Absorption of Eutectic Mixture. I. A Comparison of the Behavior of Eutectic Mixture of Sulfathiazole and that of Ordinary Sulfathiazole in Man.

Abstract: 1) Sulfathiazole forms eutectic mixtures with urea, l-ascorbic acid, acetamide, nicotinic acid, nicotinamide, or succinimide. It was observed that a eutectic mixture of sulfathiazole and urea produces a microcrystalline suspension of sulfathiazole in water. 2) Sulfathiazole in a eutectic mixture with urea shows higher absorption and excretion after oral administration than ordinary sulfathiazole. 3) Since urea does not possess solubilizing action on sulfathiazole and also it does not enhance absorption of the drug physiologically, the accelerated absorption or excretion must be attributed to the physical state of sulfathiazole in its eutectic mixture with easily soluble compound, such as urea. 4) It is assumed that this new form of preparation will give a means of adjusting therapeutic effect of medical compounds.

Studies on Absorption and Excretion of Drugs. I. Kinetics of Penetration of Acidic Drug, Salicylic Acid, through the Intestinal Barrier in vitro.

Abstract: 1. A penetration of salicylic acid through the rat small intestine was investigated from the standpoint of chemical kinetics in vitro. 2. Theoretical equations were derived from the assumption that the intestinal barrier was partially permeable to both the undissociated and dissociated forms of the drug. 3. From the data obtained, the respective permeability coefficients for the undissociated and dissociated forms of salicylic acid, Pu and Pi, were statistically determined. The estimated value of Pu was 0.0125 (cc./cm./min.) and that of Pi 0.00233 (cc./cm./min.). 4. As there was a little difference between the observed and the calculated values, an experiment at the equilibrium state was tried for the purpose of elucidating the cause of the difference. 5. The results indicate that salicylic acid is transferred across the intestinal barrier with specific coefficient for both forms of drug, Pu and Pi, that the ratio for Pu/Pi is about 6, and the relative rapid penetration of the dissociated form can be attributed to the above ratio.

Spectrophotometric Studies on Organic Substances. IX. Ultraviolet Absorption Spectra of Derivatives of Heterocyclic N-Oxides. General Properties on the Solvent Effect and the Substituting Effect.

Abstract: Ultraviolet absorption spectra and fluorescence spectra of many derivatives of benzene and naphthalene heterocyclic N-oxides and a few derivatives of anthracene and phenanthrene heterocyclic N-oxides were recorded in various solvents. Experimental results were discussed from the point of solvent effect and substituting effect. Ultraviolet spectra of all N-oxides used showed increasing blue shift with increasing polarity of the solvent. These results agreed well wlth the behavior in the solvent effect which was reported in previous papers for basic heterocyclic N-oxides and their simple derivatives. It is suggested that this solvent effect is a general property for heterocyclic N-oxides. As for the fluorescence spectra of N-oxides, such a general property as was observed on ultraviolet spectra was not observed. A main reason for this solvent effect is attributed to hydrogen bonding such as eN→OeH (in solvent). On the other hand, a relationship was found to exist between the effect of substituting positions and the spectra. By arranging many substituents in the order of substituting ability and classifying the positions in a molecule belonging to two ring systems into two classes, it has been found that the above relationship is present between 1Lb and 1La absorption bands. This property may also be considered as a general property.

Structure of Amidinomycin.

Abstract: Acid hydrolysis of amidinomycin gives two Ninhydrin-positive compounds, a new amino acid, 3-aminocyclopentanecarboxylic acid, and a base, 2-amidinoethylamine. The name of cyclopentaminin is given for the new amino acid, and its characters and synthetic method are described. The structure of N-(2-amidinoethyl)-3-aminocyclopentanecarboxamide is proposed for amidinomycin.

Studies on Nucleosides and Nucleotides. II. Synthesis of Glycosyl-2-thiothymines from Glycosylthioureas.

Abstract: Synthesis of glycosyl-2-thiothymine from glycosylthiourea was carried out. Acetylation of 1-β-D-glucopyranosylthiourea with acetic anhydride, glacial acetic acid, and perchloric acid was found to give 1-(tetra-O-acetyl-β-D-glucosyl) thiourea and it was condensed with 2-methyl-3-methoxyacryloyl chloride. Cyclization of its product afforded 1-β-D-glucopyranosyl-2-thiothymine. In a similar manner, thiourea, prepared from tri-O-benzoyl-D-ribofuranosyl chloride through isothiocyanate, afforded 1-β-D-ribofuranosyl-2-thiothymine by the same method. The structure of all the compounds synthesized was established.

Synthetic Approaches to Calycanthaceae Alkaloids. II. A Synthesis of 1, 1'-Dimethyl-3, 3'-bis (2-aminoethyl)-3, 3'-bioxindole.

Abstract: Alkylation of 1, 1'-dimethyl-3, 3'-bioxindole (V) was carried out. A higher-melting isomer (VIIa) was obtained by dimethylation of (V) with sodium hydride in benzene. while a lower-melting isomer (VIIb) was obtained by dimethylation of (V) with sodium amide in liquid ammonia. Cyanomethylation of (V) with sodium hydride in benzene afforded (VIIIa), which was further cyanomethylated by chloroacetonitrile with potassium carbonate, sodium iodide, and acetone to give (IX), which was also obtained by direct biscyanomethylation with the latter reagents. Two other 3, 3'-disubstituted 3, 3'-bioxindoles (X, XII) were also prepared by analogous alkylation. The compound (III), which was considered to be an attractive intermediate for the synthesis of (I) and (II), was obtained by catalytic reduction of (IX).

Biochemical Studies on Thiosugars. II. Synthesis of N-Acetyl-1-thio-D-glucosamine and its Derivatives.

Abstract: A convenient synthesis for 2-acetamido-2-deoxy-3, 4, 6-tri-O-acetyl-α-D-glucopyranosyl chloride was described. Several derivatives of 1-thio-D-glucosamine were synthesized through xanthate.

Studies on Fungal Polysaccharides. III. Chemical Structure of the Capsular Polysaccharide from Cryptococcus neoformans.

Abstract: The chemical structure of the capsular polysaccharide from Cryptococcus neoformans was further investigated by periodate oxidation and methylation. Periodate oxidation of the polysaccharide produced formic acid and formaldehyde, and the xylose and glucuronic acid were attacked, but a part of mannose was resistant. Hydrolysis of the methylated polysaccharide gave 2, 3, 4-tri-O-methyl-D-xylose, 2, 3, 6-tri-O-methyl-D-monnose, 2, 3, 4-tri-O-methyl-D-glucuronic acid, and 3, 6-di-O-methyl-D-mannose in 1 : 1 : 1 : 2 ratio. From these results, the chemical structure of this polysaccharide was proposed.

Studies on Fungal Polysaccharides. II. On the Componental Sugars and Partial Hydrolysis of the Capsular Polysaccharide from Cryptococcus neoformans.

Abstract: Capsular polysaccharide of the Cryptococcus neoformans was found to be a xyloglucu-ronomannan, which consisted of D-glucuronic acid, D-xylose, and D-mannose (in 1 : 1 : 3 ratio), and its molecular weight was about 6600 by the Akiya-Barger's method and from results of end-group assay. D-Xylose and a part of D-glucuronic acid in this polysaccharide were liberated more easily than D-mannose.

Uber die Synthese und die Chelatkomplexe von N-2-Pyrrolylethylenaminen.

Abstract: Es wurden N-2-Pyrrolylmethylen-anilin, -p-toluidin, -1-naphthylamin, -2-naphtyh1-amin, -p-anisidin, -p-anisidin, -p-phenetidin, -p-chloranilin und -p-bromanilin dargestellt. Schwach basische Amine, z.B. p-Nitroanilin und m-Aminobenzolsulfonsaure, reagierten nicht mit2-Pyrrolcarboxaldehyd. did erhalenen N-2-Pyrrolylmethylenamine erzeugten mit Eisen(III)und einigen anderen Metallen gefarbte Nideershlage, die in Essigsaure Athylester loslich waren. N-(1-Methyl-2-pyrrolylenthylen)-p-toluidin verhielt sich anders als das unsubstituierte Imin (II). Die Kupferchelate sind tiefbhlaue bzw. schwarze Kristalle, die in essigsaure Athylester die Absorptionsmaxima bei 350∼280mμ haben, und enthalten Kupfer und Liganden im Verhaltnis von 1 : 2. Bei der Komplexbildung verschob sich nach wenigen Frequenzen bei 10 bis 20 cm-1 die C=N Bande in der Nahe 1620cm-1.

Synthesis of Potential Anticancer Agents. VII. 6-Nitro- and 6-Amino-s-triazolo [2, 3-α] pyrimidines.

Abstract: By nitration of s-triazolo [2, 3-α] pyrimidine derivatives, four kinds of 6-nitro derivatives (Va, VIa, VIIa, and VIIIa) were obtained. These nitro compounds were converted to the corresponding 6-amino derivatives by catalytic reaction and the nature of the amino group at 6-position was examined. 2-Acetamido-1, 3-dicarbonyl compounds were condensed with 5-amino-s-triazole (IX) into 6-acetamido-s-triazolo [2, 3-α] pyrimidines (VIc, VIIc, and VIIIc), which were converted into the corresponding 6-amino derivatives by hydrolysis.

Uber die Synthese von N1-substituierten N3-Acylguanidinen (Vorlaufige Mitt.). Benzoylverbindungen.

Abstract: Es wird eine allgemeine Methode beschrieben, nach der aliphatische und aromatische Amine durch einstufige Reaktion mittels 2-Methyl-3-benzoylisothioharnstoffs in die entsprechenden Monobenzoylguanidin-derivate ubergefuhrt werden konnen.

Studies on Fungal Polysaccharides. I. On the Isolation and Chemical Properties of Capsular Polysaccharide from Cryptococcus neoformans.

Abstract: Capsular polysaccharide of Cryptococcus neoformans CRD-1 was isolated by Einbinder's method and purified by zone electrophoresis with starch gel and borate buffer (pH 10.0) or acetate buffer (pH 5.0). This material (potassium salt) showed physical constants of [α]15D +15.5° (c=0.775) and [η]=20 (c=g./100 cc.), and was positive to Molisch, Bial, and naphthoresorcinol reactions, but negative to iodine, biuret and Ninhydrin reactions. On infrared spectrum, its potassium salt showed the presence of carboxylate ion.