Showing papers in "Chemical & Pharmaceutical Bulletin in 1979"

A New Mast Cell Degranulating Peptide "Mastoparan" in the Venom of Vespula lewisii

Abstract: The new mast cell degranulating peptide "mastoparan" was isolated from the venom of Vespula lewisii (Vespid wasp) and the peptide was synthesized chemically. Mastoparan is tetradecapeptide amide constituted of the restricted amino acid and the repeated sequence.

The constituents of Schizandra chinensis Baill. I. Isolation and structure determination of five new lignans, gomisin A, B, C, F and G, and the absolute structure of schizandrin.

Abstract: Five new dibenzocyclooctadiene lignans, named gomisin A (2), B (3), C (4), F (5) and G (6), were isolated from the petroleum ether extract of fruits of Schizandra chinensis BAILL. (Schizandraceae) and their absolute structures were elucidated by chemical and spectral techniques. The absolute structure of schizandrin (1), the plane structure of which had already been elucidated by Kochetkov et al., was also elucidated on the basis of spectroscopic results.

Synthesis of New Water-soluble Dihydropyridine Vasodilators

Abstract: Several kinds of water-soluble dihydropyridine vasodilators were prepared and their vasodilating activities were evaluated. Among them, 2-(N-benzyl-N-methylamino)-ethyl methyl 2, 6-dimethyl-4-(m-nitrophenyl)-1, 4-dihydropyridine-3, 5-dicarboxylate hydrochloride (YC-93) was found to have outstanding activity and bioavailability. Various synthetic routes for this compound were examined.

Purification and Properties of Oxalate Oxidase from Barley Seedlings

Abstract: Oxalate oxidase from barley seedlings (Hordeum vulgare L. var. distichon ALEFELD) was purified to homogeneity as determined by disc gel electrophoresis. The enzyme hydrolyzed oxalate, but no other related acids. The optimum pH was around pH 3.5, and this enzyme was stable at acidic pHs. The enzyme appears to consist of two identical subunits. Various other properties were investigated.

Hypotensive Principles of Diospyros kaki Leaves

Abstract: The extract of a traditional Oriental medicine"kaki-yo, "Diospyros kaki leaves, was fractionated, monitoring for hypotensive activity against urethane-anesthetized rats ; astragalin and isoquercitrin were obtained as the active principles.

Drug-carrier Property of Albumin Microspheres in Chemotherapy. II. Preparation and Tissue Distribution in Mice of Microsphere-entrapped 5-Fluorouracil

Abstract: Bovine serum albumin microspheres contatining 5-fluorouracil-6-3H were prepared by heating at 180° (or 150°, 100°) of 25% albumin solution in cottonseed oil emulsion. The shape of this microsphere was invariably spherical, and the average diameter was 0.66μ. After intravenous injection in mice, 5-fluorouracil-6-3H entrapped in albumin microspheres localized mainly in the liver, and the disappearance rate of radioactivity in microspheres from the tissue was very slow in comparison with that of free drugs. The microsphere might be delivered into reticuloendothelial system in the liver because ofits phagocytic activity, as well as the distribution following injection of albumin macroaggregates. Such preferential localization and sustained release of entrapped drugs suggested that albumin microspheres are useful as drug-carrier in chemotherapy.

Further study on dammarane-type saponins of roots, leaves, flower-buds, and fruits of Panax ginseng C.A. Meyer

Abstract: New saponins, named ginsenosides-Rh1 (11) and -M7cd (17) were isolated from roots and flower-buds of Ginseng, repectively. Structures of 11 and 17 were established as 6-O-β-D-glucopyranoside of 20 (S) -protopanaxatriol and 20-O-β-D-glucopyranoside of dammar-25-ene-3β, 6α, 12β, 20 (S), 24ξ-pentaol, respectively by means of carbon-13 nuclear magnetic resonance spectroscopy as well as their preparations from the known saponins. Further isolation and identification of the following dammarane-type saponins from the aerial parts of Ginseng were also reported : ginsenosides-Rb1 (1), -Rb2 (2), -Rc (4) from the leaves ; 1, 2, 4, and ginsenoside-F3 (15) from the flower-buds, and 2, 4, ginsenosides-Rd (5), -Re (6), and -Rg1 (8) from the fruits. As shown in Table II, isolation of these biologically active saponins in relatively high yields indicated the significance of the aerial parts of Ginseng as the good medicinal sources.

Synthetic Nucleosides and Nucleotides. XIII. Stannic Chloride Catalyzed Ribosylation of Several 6-Substituted Purines

Abstract: Condensation of adenine (1a) with 1-O-acetyl-2, 3, 5-tri-O-benzoyl-β-D-ribofuranose (2a) in acetonitrile in the presence of stannic chloride at room temperature gave blocked nucleoside. After removal of the benzoyl group, adenosine (4a) was obtained in 78% overall yield. When 1, 2, 3, 5-tetra-O-acetyl-β-D-ribofuranose (2b) was used instead of 2a in the same reaction, 2', 3', 5'-tri-O-acetyladenosine (3b) was obtained in 77% yield. In both cases, the α-isomer or 1-, 3- or 7-riboside could not be detected in the reaction. In an application of this reaction, 6-chloropurine (1b) and purin-6-yl benzyl disulfide (1c) were coupled with 2a or 2b followed by reaction with thiourea or β-mercaptoethanol to give 2', 3', 5'-tri-O-acyl-6-thioinosine (3c). Coupling of 6-methylthiopurine (1d) with 3a after deblocking of the acyl group yielded 9-β-D-ribofuranosyl-6-methylthiopurine in 75% yield. In addition, 2, 6-dichloropurine (1e) coupled with 2b under the same conditions to give 9-β-D-ribofuranosyl-2, 6-dichlororopurine tri-O-acetate in 81% yield.

Anti-ulcer effect of isoprenyl flavonoids. II. Synthesis and anti-ulcer activity of new chalcones related to sophoradin.

Abstract: To investigate the anti-ulcer activity of the isoprenyl chalcone, sophoradin, which is present in a Chinese crude drug, Guang-dou-gen (the root of Sophora subprostrata), 30 related chalcones (1-30) were newly synthesized by condensation between substituted acetophenones and benzaldehydes, and their anti-ulcer activities were examined using Shay's pylorus-ligated rats, and water-immersed and restraint stress rats. Twenty-seven chalcones were substituted with isoprenyl or isoprenyloxyl groups and two with geranyloxyl groups (13, 30), with or without a carboxymethoxyl group, and one chalcone was substituted with allyloxyl group (14). All the chalcones were found to be effective by both methods. Several chalcones (2, 3, 8, 10, 11, 12, 15, 17, 22), each having more than one isoprenyloxyl group, exhibited high inhibitory ratios by both methods. In particular, 2', 4'-dihydroxy-3'-(3-methyl-2-butenyl)-4-(3-methyl-2-butenyloxy) chalcone (2), 2'-hydroxy-4, 4'-bis (3-methyl-2-butenyloxy) chalcone (10), and 2'-carboxymethoxy-4, 4'-bis (3-methyl-2-butenyloxy) chalcone (15) exhibited very high inhibitory ratios (70-100%) by both methods, and were as potent as sophoradin.

Carbon-13 nuclear magnetic resonance of 24-substituted steroids.

Abstract: ^ C-NMR spectra of epimeric pairs of 24-hydroxy-, 24, 25-dihydroxy-, 1, 24-dihydroxy-, 24-methyl-and 24-ethyl-cholesterols were measured and the signals of all carbons assigned. Most of the side chain carbons in the C-24 epimeric mixtures showed split signals and characteristic differences between 24R and 24S isomers were recognized for the C-20 and C-24 signals, these resonances in the 24R compounds being always at slightly higher field than in the 24S isomers.

Antioxidant properties of branched-chain amino acid derivatives.

Abstract: The antioxidant activities of branched-chain amino acid derivatives, such as dipeptides and amino alcohols, were evaluated by means of the active oxygen method. Dipeptides containing a branched-chain amino acid showed higher antioxidant activities than did those having no branched-chain amino acid. An N-terminal branched-chain amino acid in dipeptides was preferable to a C-terminal one for antioxidant activity. A free N-terminal amino group was also found to be important for the appearance of antioxidant activity.

Marine Terpenes and Terpenoids. I. Structures of Four Cembrane-type Diterpenes : SarCophytol-A, Sarcophytol-A Acetate Sarcophytol-B, and Sarcophytonin-A, from the Soft Coral, Sarcophyton glaucum

Abstract: The lipid extract of the soft coral, Sarcophyton glaucum, was found to contain significant amounts of cembrane-type diterpenes. The structures of four major components, sarcophytol-A, sarcophytol-A acetate, sarcophytol-B, and sarcophytonin-A were characterized on the basis of spectral data and degradative studies by ozonolysis. Sarcophine and 16-deoxosarcophine, which were reported to be abundant in S. glaucum collected in the Red Sea, were not found yet.

The Constituents of Schizandra chinensis BAILL. V. The Structures of Four New Lignans, Gomisin N, Gomisin O, Epigomisin O and Gomisin E, and Transformation of Gomisin N to Deangeloylgomisin B

Abstract: Four new dibenzocyclooctadiene lignans, gomisins N (1), O (2) and E (4), and epigomisin O (3), together with a known lignan (+)-deoxyschizandrin (5) were isolated from the fruits of Schizandra chinensis BAILL (Schizandraceae) The structures of the new lignans were elucidated by chemical and spectral studies The transformation of 1 to deangeloylgomisin B (debenzoylgomisin C) (6) is also described

Synthesis of Disulfates of Unconjugated and Conjugated Bile Acids

Abstract: The disulfates of unconjugated, and glycine- and taurine-conjugated bile acids have been synthesized. Cholic acid derivatives appropriately protected were sulfated with sulfur trioxide-triethylamine complex in pyridine in the usual manner. Subsequent hydrolysis and/or sodium borohydride reduction provided the desired disulfates of cholates in satisfactory yields. Dihydroxylated bile acid disulfates were also prepared. The nuclear magnetic resonance spectral data for bile acid disulfates and related compounds are tabulated.

The preparation of steroid N-hydroxysuccinimide esters and their reactivities with bovine serum albumin.

Abstract: The N-hydroxysuccinimide esters of testosterone and cortisol were prepared from the corresponding carboxylic acid derivatives by a carbodiimide method. These activated esters were covalently linked to bovine serum albumin in organic solvent/phosphate buffer (pH 7.4) employing various molar ratios of the steroid to protein. The results indicated that the activated ester method would be useful for enzyme labeling in enzyme immunoassay of steroids in respects of simplicity and reproducibility.

The Constituents of Schizandra chinensis BAILL. IX. The Cleavage of the Methylenedioxyl Moiety with Lead Tetraacetate in Benzene, and the Structure of Angeloylgomisin Q

Abstract: A procedure for selective cleavage of the methylenedioxyl moiety with lead tetraacetate in dry benzene is described. Piperonylic acid methyl ester (5), 4-nitro-1, 2-methylenedioxybenzene (6), 3, 4-methylenedioxytoluene (7), 2, 3-methylenedioxyanisole (8) and gomisin A (9) afforded protocatechuic acid (12), 4-nitrocatechol (13), 3, 4-dihydroxytoluene (14), 2, 3-dihydroxyanisole (15) and compound 16, respectively. The structure of angeloylgomisin Q isolated from the fruits of Schizandra chinensis BAILL. (Schizandraceae), was elucidated as 1 by using the above reaction.

Interaction of drugs with bile components. I. Effects of bile salts on the dissolution behavior of indomethacin and phenylbutazone.

Abstract: The effects of bile salts on the dissolution behavior of indomethacin and phenylbutazone were investigated. Bile salts such as sodium desoxycholate and sodium cholate considerably enhanced the dissolution of both drugs in pH 7.3 buffer at 37°. The results indicated that the enhancement of the dissolution of indomethacin in the presence of bile salts was mainly due to micellar solubilization. On the other hand, the enhanced dissolution of phenylbutazone may be due to the wetting effect, increasing the effective surface area of the powder.

Biological Fate of Butylated Hydroxytoluene (BHT) : Binding in Vitro of BHT to Liver Microsomes

Abstract: The binding of 14C-labeled butylated hydroxytoluene (14C-BHT) to the liver microsomes was studied in vitro. Binding of 14C-BHT to microsomal macromolecules was linear with time and protein concentration. Oxygen and dihydronicotinamide adenine dinucleotide phosphate (NADPH) were necessary for this binding, while carbon monoxide or SKF-525A inhibited it. It is indicated that a cytochrome P-450-linked monooxygenase system mediated the binding. In addition the binding was more pronounced in the liver microsomes from animals pretreated with inducers (phenobarbital or BHT) of microsomal monooxygenase system. From the effects of pretreatment with these inducers, it is suggested that a cytochrome P-450 with a high BHT oxidase activity is mainly responsible for the metabolic activation of BHT in the liver microsomes. The microsomes in the brain, kidneys and spleen were devoid of BHT-binding capacity, but in the lung microsomes the binding capacity was about 40% of that in the liver microsomes.

Stereoselective Reactions. I. A highly Efficient Asymmetric Synthesis of β-Substituted Aldehydes via 1, 4-Addition of Grignard Reagents to optically Active α, β-Unsaturated Aldimines

Abstract: The 1, 4-addition of Grignard reagents to the chiral α, β-unsaturated aldimines (3d, e), prepared from α, β-unsaturated aldehydes (1) and optically active tert-leucine tert-butyl ester (2d), afforded, after hydrolysis, optically active β-substituted aldehydes (4) in 91-98% enantiomeric excess. The present method has advantages in giving aldehydes (4) in high enantiomeric purities, allowing easy preparation of the aldimines as well as easy recovery of optically active tert-leucine tert-butyl ester (2d) without any racemization for reuse, and exhibiting general utility. The possible mechanism of the reaction, by which the absolute configuration of the aldehydes (4) is unequivocally predictable, is proposed.

Asymmetric Halolactonization Reactions. 3. Asymmetric Synthesis of optically Active Anthracyclinones

Abstract: The asymmetric bromolactonization of (S)-N-(α, β-unsaturated) acylproline ((S)-17a) prepared from the α, β-unsaturated acid (10a) was found to occur stereoselectively to give the bromolactone (18a) in which one diastereomer (18Aa) was predominant. Debromination of 18a followed by acidic hydrolysis, afforded the (R)-α-hydroxy acid ((R)-12a) in 92% optical purity. Reaction of (R)-12a with methylithium gave the (R)-α-hydroxy ketone ((R)-9a), a model compound of the optically active anthracyclinone AB ring system, in good yield. When the reaction scheme established by the model study was applied to 10b, c, which possess the AB and ABCD ring systems of anthracyclinones (2), (R)-α-hydroxy acid methyl esters ((R)-21b, c) could be prepared in 97% and 87% optical yields, respectively. Alkaline hydrolysis of optically pure (R)-21b, c independently prepared from the pure debrominated lactones (19Ab, c) gave (R)-12b, c. Although the reaction of tetracyclic (R)-12c with methyllithium did not proceed in the expected manner, bicyclic (R)-12b was successfully converted to optically pure (R)-9b, which has previously been utilized as a starting material for the synthesis of optically active natural and unnatural 2.

Preparation and Phase II Clinical Examination of Topical Dosage Form for Treatment of Carcinoma Colli Containing Bleomycin with Hydroxypropyl Cellulose

Abstract: A new topical disk-like dosage form for carcinoma colli was prepared by direct compression of the mixture of bleomycin hydrochloride (BLM) and combination of hydroxypropyl cellulose (HPC) and other water soluble polymer. After in vitro examinations regarding the water adsorption, the release and dissolution of drug and other properties, the preparations were examined clinically by applying to the voluntary patients. A combination of HPC and Carbopol 934 (CP) seemed preferable as the vehicles, and the amount of BLM released from the preparation increased remarkably with an increase in concentration of HPC. In contrast, the water absorbing property increased with an increase of CP. The preparation containing 30 mg of BLM, for which the preparative formula was designed according to the in vitro experiment, was administered to the voluntary patients of carcinoma colli of stage O to Ib. The preparation taken out of patient indicated the continuous release of BLM for longer than 24 hr. In the three of nine patients, any cancerous focus was not found after the local therapy using 90 to 195 mg of BLM in total, and remnant foci found in the other six patients were very few. Moreover, the normal mucosa was not affected by BLM, contrary to the case of usual suppositories reported. The higher per cent of cure might be expected if the therapy could be continued for the longer period.

Dissolution mechanisms of drug-polyvinylpyrrolidone coprecipitates in aqueous solution.

Abstract: Coprecipitates of sulfamethizole-polyvinylpyrrolidone (PVP) and sulfisoxazole-PVP were prepared at various ratios. The dissolution rates of the drugs in the coprecipitates were greater when the ratio of drug to PVP was smaller. The dissolution rate of sulfamethizole in the coprecipitate was greater when PVP of smaller molecular weight was used. Dissolution patterns were different for sulfamethizole-PVP coprecipitate and sulfisoxazole-PVP coprecipitate ; recrystallization of the drug was observed following the dissolution of sulfisoxazole-PVP coprecipitate, whereas no recrystallization was found in the dissolution of sulfamethizole-PVP coprecipitate. A new dissolution model for coprecipitate is proposed.

The constituents of Schizandra chinensis Baill. II. The structure of a new lignan, gomisin D.

Abstract: A new dibenzocyclooctadiene lignan, named gomisin D (1), was isolated from the petroleum ether extract of the fruits of Schizandra chinensis BAILL. (Schizandraceae), and its structure was elucidated on the basis of chemical and spectral evidence. The absolute structure of gomisin D was determined by X-ray analysis of its 4, 11-dibromo-derivative (4).