Showing papers in "Chemical & Pharmaceutical Bulletin in 1989"

Effects of the Interaction of Tannins with Co-existing Substances. VI. : Effects of Tannins and Related Polyphenols on Superoxide Anion Radical, and on 1, 1-Diphenyl-2-picrylhydrazyl Radical

Abstract: The scavenging effects of twenty-five tannins including low-molecular polyphenols on the superoxide anion radical (O2-) generated in the hypoxanthine-xanthine oxidase system were estimated by electron spin resonance (ESR) measurements of the adducts formed by 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) and the radical. The scavenging effects of tannins and related polyphenols having ortho-trihydroxyl (pyrogallol) structure [galloyl, hexahydroxydiphenoyl (HHDP) groups in hydrolyzable tannins, galloyl group in acylated proanthocyanidins, and the B-ring of some flavan-3-ols] were stronger than the effects of unacylated proanthocyanidins. The effects of tannins and related polyphenols on the superoxide anion radical were also compared with those on the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical. Each tannin in an ethanol solution of DPPH radical reduced the intensity of the signal of the DPPH radical, and gave a weak signal assignable to a radical derived from that tannin, in a similar way to the appearance of the signal of dl-α-tocopherol radical, accompanied with reduction of the signal of DPPH radical, in a mixture of dl-α-tocopherol and the DPPH radical. In contrast to the case of the superoxide anion radical, the effects of unacylated proanthocyanidins on DPPH radical were comparable with those of the other types of tannins. The scavenging effects of all of the tannins and related polyphenols tested in the experiments on DPPH radical were stronger than that of dl-α-tocopherol.

Studies on Inhibition Mechanism of Autoxidation by Tannins and Flavonoids. V. Radical-Scavenging Effects of Tannins and Related Polyphenols on 1, 1-Diphenyl-2-picrylhydrazyl Radical

Abstract: Radical scavenging effects of tannins and related polyphenols on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical were evaluated by colorimetry. All of the polyphenols examined showed effects much stronger than that of α-tocopherol.The hydrolyzable tannins having galloyl groups in the molecule exhibited stronger effects than those having modified galloyl groups, such as hexahydroxydiphenoyl (HHDP), dehydrohexahydroxydiphenoyl (DHHDP) and chebuloyl groups. (-)-Epigallocatechin gallate, (-)-epigallocatechin, (-)-epicatechin gallate and methyl gallate also showed fairly significant effects, even though they are small molecules. The predominant reaction products upon the treatment of various alkyl gallates with DPPH radical on a preparative scale were dialkyl hexahydroxydiphenates, which should be formed by mutual coupling of C-centered galloyl radicals. Evidence for the formation of the alkyl gallate radicals was also obtained by the electron spin resonance spectroscopy.

Metabolites of Penicillium italicum WEHMER : Isolation and Structures of New Metabolites Including Naturally Occurring 4-Ylidene-acyltetronic Acids, Italicinic Acid and Italicic Acid

Abstract: Four new metabolites, italicic acid, dihydro-italicic acid, methyl italicate and italicinic acid, were isolated from culture medium of Penicillium italicum WEHMER. The structures, possessing a 4-ylidene-acyltetronic acid unit, and their biosynthesis were elucidated. Two other new metabolites possessing a chromone skeleton were also isolated and their structures were established as 6, 7-dihydroxy-3-(1'-hydroxy-3'-butanoyl)chromone-5-carboxylic acid and its 1', 2'-dehydrate.

Cytotoxic triterpenes from a Chinese medicine, Goreishi

Abstract: Bioactivity-guided fractionation of the methanol extract of Goreishi (the feces of Trogopterus xanthipes Milne-Edwards) afforded one new and three known cytotoxic triterpenes, namely, 3-O-cis-p-coumaroyltormentic acid, pomolic acid, 2 alpha-hydroxyursolic acid, and jacoumaric acid. In the course of this investigation, six additional compounds having no cytotoxic activity were isolated, namely, maslinic acid, 3-O-trans-p-coumaroylmaslinic acid, ursolic acid, tormentic acid, euscaphic acid, and a new triterpene, 3-O-trans-p-coumaroyltormentic acid. The structures of the new compounds were established on the basis of X-nucleus-proton correlation with fixed evolution time (XCORFE) and other spectroscopic evidence.

Studies on the Biological Activity of Tocotrienols

Abstract: Tocotrienols were evaluated for activity against transplantable murine tumors inoculated i.p. into mouse, and the activities of two tocotrienols and α-tocopherols were compared. When the compounds were injected i.p., α- and γ-tocotrienols were effective against sarcoma 180, Ehrlich carcinoma, and IMC carcinoma, and γ-tocotrienol showed a slight life-prolonging effect in mice with Meth A fibrosarcoma, but the tocotrienols had no antitumor activity against P388 leukemia at doses of 5-40 mg/kg/d. On the other hand α-tocopherol had only a slight effect against sarcoma 180 and IMC carcinoma. The antitumor activity of γ-tocotrienol was higher than that of α-tocotrienol. Tocotrienols showed growth inhibition of human and mouse tumor cells when the cells were exposed to these agents for 72h in vitro, whereas tocopherol did not show any marked cytotoxic activity. Alpha- and γ-tocotrienols had inhibitory effects on lipid peroxidation of murine microsomes by adriamycin.

Tannins and Related Compounds. XC. : 8-C-Ascorbyl (-)-Epigallocatechin 3-O-Gallate and Novel Dimeric Flavan -3-ols, Oolonghomobisflavans A and B, from Oolong Tea. (3)

Abstract: A chemical examination of the polypenolic constituents in commercial oolong tea has led to the isolation of a new-flavan-3-ol, two novel dimeric flavan-3-ols named oolonghomobisflavans A and B eight new proanthocyanidins, together with twenty-one known polyphenols including proanthocyanidins, hydrolyzable tannins and red pigments. On the basis of chemical and spectroscopic evidence, the flavan-3-ol has been characterized as 8-C-ascorbyl (-)-epigallocatechin 3-O-gallate (22), while oolonghomobisflavans A (26) and B (27) have been determined to be dimeric flavan-3-ols in which two units are linked through a methylene bridge at the 8, 8'- and 8, 6'-positions, respectively. The structures of the new proanthocyanidins were elucidated mainly by tannase hydrolysis and thiolytic degradtion as epicatechin-(4β→8)-epigallocatechin 3-O-gallate (29), epicatechin 3-O-gallate-(4β→8)-epigallocatechin 3-O-gallate (30), catechin-(4α→8)-epigallocatechin 3-O-gallate (31), prodelphinidin B-4 3'-O-gallate (32), epicatechin 3-O-gallate-(4β→6)-epigallocatechin 3-O-gallate (33), epigallocatechin 3-O-gallate-(4β→6)-epicatechin 3-O-gallate (34), epiafzelechin 3-O-gallate-(4β→6)-epigallocatechin 3-O-gallate (35) and prodelphinidin B-2 3'-O-gallate (36).

Ganoderic acid and its derivatives as cholesterol synthesis inhibitors.

Abstract: Oxygenated lanosterol derivatives, which were isolated from Ganoderma lucidum (Polyporaceae) or their derivatives obtained by chemical conversion, were tested for their effect on cholesterol biosynthesis from 24,25-dihydrolanosterol by rat hepatic subcellular 10,000 x g supernatant fraction. The sterol (VI, 40 microM) with 7-oxo and 15 alpha-hydroxy groups potently inhibited the synthesis of cholesterol from [24,25-3H]-24,25-dihydrolanosterol (18 microM).

Phenolic constituents of licorice. II. Structures of licopyranocoumarin, licoarylcoumarin and glisoflavone, and inhibitory effects of licorice phenolics on xanthine oxidase.

Abstract: An anti-HIV (human immunodeficiency virus) phenolic constituent, licopyranocoumarin (4), and two other new phenolics named licoarylcoumarin (5) and glisoflavone (6) were isolated from Si-pei licorice (a commercial licorice; root and stolon of Glycyrrhiza sp. from the north-western region of China) using droplet countercurrent chromatography and centrifugal partition chromatography, and their structures were assigned based on chemical and spectroscopic data. Kaempferol 3-O-methyl ether (7) and licocoumarone (8) were also isolated from the licorice. The inhibitory effects of ten licorice phenolics on xanthine oxidase were examined. Licochalcone B (1), glycyrrhisoflavone (2), 8 and licochalcone A (19) showed 50% inhibition at the concentration of 1.3-5.6 x 10(-5) M.

Thermochemical Study of Theophyline and Its Hydrate

Abstract: Anhydrous theophylline exhibited polymorphism and two modifications, which were named form I and form II, were isolated. The melting point and the enthalpy of fusion of each polymorph determined by differential scanning calorimetry (DSC) were 273.4±1.0°C and 26.4±0.3 kJ/mol for form I and 269.1±0.4°C and 28.2±1.1 kJ/mol for form II. The higher melting form I had a smaller density. In contrast to caffeine, theophylline formed a monohydrate. The dissociation vapor pressure curves of theophylline hydrate and caffeine hydrate were obtained and the difference in their stabilities was discussed. The enthalpy of dehydration was determined by DSC under closed conditions. The dehydration under isothermal conditions appeared to proceed acoording to the mechanism of random uncleation followed by two-dimensional growth of nuclei as represented by the Avrami-Erofe'ev equation. The solubilities of theophylline and its hydrate were determined as a function of temperature. From the van't Hoff type plot, the transition temperature between the hydrate and the anhydrous form was determined.

Magnesium and Ammonium-Potassium Lithospermates B, the Active Principles Having a Uremia-Preventive Effect from Salvia miltiorrhiza

Abstract: The active components which exhibit the improving effect on uremic symptoms have been isolated from Salviae miltriorrhizae Radix and characterized as magnesium lithospermate (1) and ammonium-potassium lithospermate (2). The stereostructure of lithospermic acid, which had remained unclarified, was also determined on the basis of chemical and spectroscopic data.

Tannins of cornaceous plants. I. Cornusiins A, B and C, dimeric monomeric and trimeric hydrolyzable tannins from Cornus officinalis, and orientation of valoneoyl group in related tannins.

Abstract: Cornusiin A (1), cornusiin B (2) and cornusiin C (3), new dimeric, monomeric and trimeric hydrolyzable tannins, were isolated from the fruits of Cornus officinalis (Cornaceae). Their structures, including the orientation of the valoneoyl group in 1 and 3, were established on the basis of chemical and spectroscopic data. 2,3-Di-O-galloyl-D-glucose (7), 1,2,3-tri-O-galloyl-beta-D-glucose, 1,2,6-tri-O-galloyl-beta-D-glucose, 1,2,3,6-tetra-O-galloyl-beta-D-glucose, gemin D (5), isoterchebin, tellimagrandin I (6) and tellimagrandin II were also isolated from the fruits. The orientation of the valoneoyl group in camptothin A (14) and that in camptothin B (15), which had been isolated from Camptotheca acuminata (Nyssaceae), were also determined based on that in 1.

Glassy state of pharmaceuticals. III. Thermal properties and stability of glassy pharmaceuticals and their binary glass systems.

Abstract: Glassy pharmaceuticals were prepared by cooling the melts and their state was confirmed by measuring the glass transition temperature (Tg) and the anomalous endothermic peak (heat capacity maximum) in the differential scanning calorimetry (DSC) curves. Glass formation was found for 20 pharmaceuticals (aspirin, phenobarbital, antipyrine and so on). The values of the ratio of Tg and melting temperature (Tm) of these pharmaceuticals lay between 0.59 and 0.84. Although the glassy indomethacin was very stable, remaining as a glass for 2 years at room temperature, glassy phenobarbital with the same Tg as glassy indomethacin was unstable, and devitrification occurred within a week. Thus the rate of crystallization of pulverized glassy phenobarbital was determined by the X-ray diffraction method. The crystallization of pulverized glassy phenobarbital proceeded rapidly and the degree of crystallinity reached a maximum of 75% after 24 h.Crystallization of glassy salicin was followed by means of DSC curves. It was revealed that stabilization by enthalpy relaxation occurred simultaneously with the crystallization in glassy salicin during standing.Binary glass systems of pharmaceuticals were prepared with the aim of improving the stability of the glass, and several thermal properties of binary glass systems were investigated.

Motilides, macrolides with gastrointestinal motor stimulating activity. I. O-substituted and tertiary N-substituted derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal.

Abstract: Chemical modifications of 8,9-anhydroerythromycin A 6,9-hemiacetal (1), which showed gastrointestinal motor stimulating (GMS) activity 10 times more potent than that of erythromycin A (EM-A), were undertaken to search for derivatives having stronger GMS activity and no antimicrobial activity; details are described in this and a subsequent paper. Displacement of a methyl group of the dimethylamino group of 1 with an ethyl group and an isopropyl group provided de(N-methyl-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal (55) and de(N-methyl)-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (58), respectively. They showed significant GMS activity and no antibacterial activity. In particular, the GMS activity of 58 was increased to 248 times that of EM-A. EM-A and the derivatives obtained in this study mimic exogenous motilin in the dog. The name "motilide", meaning a motilin-like macrolide, is proposed for this new family of macrolide compounds.

Cross-Coupling Reactions of Chloropyrazines with 1-Substituted Indoles

Abstract: Palladium-catalyzed coupling reactions of 2-chloro-3, 6-dialkylpyrazines with 1-tosylindole gave 1-tosyl-3-(3, 6-dialkylpyrazin-2-yl)indoles as the main product in each case. The subsequent hydrolysis of the products yielded the corresponding 3(3, 6-dialkylpyrazin-2-yl)indoles under alkaline conditions. Coupling reactions of 2-chloro-3, 6-dialkyl-pyrazines with 1-methyl- or 1-benzylindole occurred at the 2-position of the indoles, but 2-chloro-3, 5-diphenylpyrazine (1e) failed to react with 1-methylindole.

Structure of an anti-plasmin inhibitor, eckol, isolated from the brown alga Ecklonia kurome Okamura and inhibitory activities of its derivatives on plasma plasmin inhibitors

Abstract: Eckol (1), a novel phlorotannin with a dibenzo-1,4-dioxin skeleton, has been isolated from the brown alga Ecklonia kurome Okamura as a potent and specific anti-plasmin inhibitor. Its structure has been elucidated based on the spectral data, in particular, by means of negative nuclear Overhauser effect (NOE), and finally established as 1-(3,5-dihydroxyphenoxy)-2,4,7,9-tetrahydroxydibenzo-1,4-dio xin by X-ray analysis. Some partially methoxylated derivatives of eckol were prepared by methylation with diazomethane and also by selective dimethylation of eckol permethylate (1b) to establish the structural requirements for inhibitory activities on alpha 2-macroglobulin and alpha 2-plasmin inhibitor, the main plasmin inhibitors in plasma.

Isoflavan and related compounds from Dalbergia odorifera. I

Abstract: Twenty-seven isoflavonoid monomer and dimer derivatives were obtained from the heartwood of Dalbergia odorifera T. CHEN (Leguminosae). The structure elucidation of twelve monomeric and five dimeric isoflavonoids is dealt with in this paper, affording novel examples of naturally occurring biisoflavonoids.

Electrokinetic chromatography for drug analysis. Separation and determination of cefpiramide in human plasma

Abstract: Electrokinetic chromatography using a fused silica capillary and sodium dodecyl sulfate (SDS) solution has been applied to the separation and determination of cefpiramide (CPM) in human plasma with the use of antipyrine (AP) as an internal standard. A plasma sample was introduced into the capillary by siphoning. The calibration plot for CPM in plasma sample showed good linearity in the concentration range over 10 to 30 μg/ml. This method has advantages over usual high performance liquid chromatography (HPLC) in that it needs only a very small volume (<10 nl) of plasma without pretreatment, and an extremely high separation effciency (10 times or much higher plate number than usual HPLC) is obtained. The addition of SDS to the supporting electrolyte solution enabled (1) rapid release of protein-bound drug which allowed the total concentration to be determined, (2) reproducible results to be obtained by suppressing adsorption of protein onto the fused silica capillary and (3) rapid separation of drug from proteins by selective retardation of protein peaks.

A nonlinear least squares program, MULTI(FILT), based on fast inverse Laplace transform for microcomputers.

Abstract: A nonlinear curve fitting program MULTI(FILT) into which the fast inverse Laplace transform (FILT) is incorporated was developed on a microcomputer. FILT is an algorithm for the numerical inversion of Laplace-transformed equations (image equations) to generate the corresponding real time courses. The pharmacokinetic models can be defined in the form of Laplace-transformed equations as a subroutine in MULTI(FILT). MULTI(FILT) achieves the numerical inversion of the defined image equations according to FILT and the subsequent curve-fitting of the inverse-transformed time courses to the experimental data points to estimate the pharmacokinetic parameters by the nonlinear least-squares method. MULTI(FILT) has a function to impose constraints on the pharmacokinetic parameters. In order to verify the reliability of MULTI(FILT), the pharmacokinetic parameters estimated by MULTI(FILT) were compared with those by MULTI using 100 time courses which were artificially generated according to the Monte Carlo method, based on data for theophylline and bishydroxycoumarin. The estimated pharmacokinetic parameters by MULTI(FILT) agreed with those by MULTI. Thus, it is suggested that FILT, developed in the field of electronic technology, is also useful in the pharmacokinetic field.

Tannins and Related Compounds. LXXVII. : Novel Chalcan-flavan Dimers, Assamicains A, B and C, and a New Flavan-3-ol and Proanthocyanidins from the Fresh Leaves of Camella sinensis L. var. assamica KITAMURA

Abstract: Three novel chalcan-flavan dimers, assamicains A (1), B (2) and C (3), and a new flavan-3-ol (14) and proanthocyanidins (19, 20) have been isolated, together with the known flavan-3-ols (4-13), proanthocyanidins(15-18, 21), theasinensins (22-24) and hydrolyzable tannins (25, 26), from the fresh leaves of Camellia sinensis var. assamica (Camelliaceae), and their structures have been established on the basis of spectroscopic evidence in conjunction with thiolytic degradation and enzymatic hydrolysis.

Identification of antimicrobial and antioxidant constituents from licorice of Russian and Xinjiang origin.

Abstract: The organic extracts of two licorices, known in commerce as Russian and Xinjiang licorices, exhibited potent antimicrobial and antioxidant activity. The bioassay-directed chemical investigation of both licorices revealed glabrene, glabridin, and licochalcones A and B as active principles.

Effect of chemical constituents from plants on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice.

Abstract: The induction of edema in the mouse ear has been established as a reliable in vivo assay for tumor promoters. Therefore, inhibitors of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema are most likely to be inhibitors of skin tumor promotion. Besides the application for this assay for the screening of compounds, it also allows comparison of the activities of groups of related compounds such as flavonoids. Results obtained in this way showed that the double bond at C-2 and C-3 of the flavonoid structure is a prerequisite for anti-tumor-promoting activity, and indicated that activity in this screening assay for inhibitors of TPA-induced ear edema reflects the anti-tumor-promoting effect in two-stage carcinogenesis.

Interaction of Calcium-Induced Alginate Gel Beads with Propranolol

Abstract: The loading capacity of calcium-induced alginate gel beads for propranolol, selected as a cationic model drug, was investigated with particular attention to the effects of excess Ca2+ in the beads, pH and drug concentration in the bulk solution. The amount of the drug loaded in the excess Ca2+ -washed beads was higher than that in the corresponding unwashed beads. Decreasing the pH from 4 to 1 induced size contraction of the washed beads, for which changes of the fraction of ionized carboxyl groups of the polymer seemed to be responsible, and the pKa value was estimated to be 2.8. The drug loading increased in a sigmoid mode with increasing bulk drug concentration when loaded at pH 3-4. It is especially noteworthy that the dramatic increase of the drug loading was accompanied with abrupt contraction of the beads and transformation from a slightly translucent bead body to whitish beads in the vicinity of the inflexion point, and reached a saturated level that depended on the pH. Such physical appearance changes seemed to be due to the precipitation of the drug-polymer complex in the beads but it did not show crystalline nature. The loading capacity could be controlled by adjusting the pH of the medium, and the precipitated form of the drug possibly acts as a good reservoir for efficient drug release.

Antitumor and Immunomodulating Activities of a β-Glucan Obtained from Liquid-Cultured Grifola frondosa

Abstract: The effects of the beta-1,3-glucan, LELFD, obtained from liquid-cultured mycelium of Grifola frondosa, on the growth of syngeneic tumors and immune responses in mice were examined. In Meth A or IMC solid tumor systems, LELFD administered intraperitoneally (i.p.) or intralesionally (i.l.) exhibited significant antitumor effects. However, the growth of L1210 and P388 leukemias was unaffected by the injection of LELFD. The injection of LELFD i.p. enhanced the activities of natural killer cells and macrophages in mice. LELFD also enhanced the antibody response when it was injected i.p. with sheep red blood cells into mice. Furthermore, it was found that LELFD could activate the alternative complement pathway.

Tannins and Related Compounds. LXXXIV. : Isolation and Characterization of Five New Hydrolyzable Tannins from the Bark of Mallotus japonicus

Abstract: A chemical examination of the bark of Mallotus japonicus (THUNB.) MUELLER-ARG. (Euphorbiaceae) has led to the isolation of five new hydrolyzable tannins (16-20), together with fourteen known tannins (1-14). On the basis of chemical and spectroscopic evidence, the structures of compounds 16 and 17 were established as 1, 2-di-O-galloyl -3, 6-(R)-hexahydroxydiphenoyl-β-D-glucose and 1-O-digalloyl-3, 6-(R)-hexahydroxydiphenoyl-β-D-glucose, respectively, while compounds 18 (mallojaponin) and 19 (mallonin) were shown to be 1-O-galloy-2, 4-elaeocarpusinoyl-3, 6-(R)-valoneayl-β-D-glucose and 1-O-galloyl-2, 4-elaeocarpusinoyl-β-D-glucose. Compound 20 (mallotusinin) was characterized as a novel ellagitannin which possesses a unique 1, 1'-(3, 3', 4, 4'-tetrahydroxy)dibenzofurandicarbozyl group. On the other hand, examination of the leaves revealed the presence of hydrolyxable tannins (8-10, 12-15) all containing a β-D-glucopyranose core with 1C4-conformation. Furthermore, the orientation of the valoneayl group in mallotinic acid (13) and mallotusinic acid (14), which had remained unclarified, was determined on the basis of 1H-13C shift correlation spectral analysis and chemical correlations.

Factors affecting the bioadhesive property of tablets consisting of hydroxypropyl cellulose and carboxyvinyl polymer.

Abstract: The bioadhesive property of tablets consisting of hydroxypropyl cellulose (HPC) and carboxyvinyl polymer (CP) was investigated using the mouse peritoneal membrane. The adhesion force was significantly affected by the mixing ratio of HPC and CP in the tablet, and the weakest adhesion force was observed at the ratio of 3:2 (HPC:CP). Interpolymer complex formation was confirmed between HPC and CP in the acidic medium by turbidity and viscosity measurements. The interaction between CP carboxyl groups and HPC molecules was considered to be a possible mechanism for this complex formation on the basis of a Fourier-transform infrared spectroscopy. These observations suggested that the adhesion force of the HPC--CP tablet to the mucous membrane was significantly affected by the interpolymer complex formation between HPC and CP.

A quantitative structure-activity relationship for antitumor activity of long-chain phenols from Ginkgo biloba L.

Abstract: With the aim of obtaining compounds with strong antitumor activity, a quantitative structure-activity relationship (QSAR) of antitumor phenolic compounds (long-chain phenols) was derived using the Hansch-Fujita equation. The ED50 values against Chinese hamster V-79 cells were analyzed in terms of log P as the hydrophobic parameter and the energy of the lowest unoccupied molecular orbital (ELUMO) calculated by using the modified neglect of differential overlap (MNDO) method as the electronic parameter, by means of multiple regression analysis. It was found that the activities mainly depended on log P (an optimum log P of 8.3) and a low-lying ELUMO value. 4-Undecylcatechol, selected on the basis of the above results, exhibited strong antitumor activity against Sarcoma 180 ascites and P-388 lymphocytic leukemia.

Saponins from Leaves of Acanthopanax senticosus HARMS., Ciwujia. II. : Structures of Ciwujianosides A1, A2, A3, A4 and D3

Abstract: Further investigation of the chemical constituents of the leaves of Acanthopanax senticosus HARMS. resulted in the isolation of five new triterpenoid saponins, named ciwujianosides A1 (1), A2 (2), A3 (3), D3(4) and A4 (5). The structures of these saponins were elucidated as follows : 1, 3-O-β-glucopyranosyl-(1→2)-α-arabinopyranosyloleanolic acid 28-O-α-rhamnopyranosyl-(1→4)-β-glucopyranosyl-(1→6)-β-glucopyranosyl ester; 2, 3-O-β-glucopyranosyl-(1→2)-α-arabinopyranosyl-30-norolean-12, 20(29)-dien-28-oic acid 28-O-α-rhamnopyranosyl-(1→4)-β-glucopyranosyl-(1→6)-β-glucopyranosyl ester; 3, 3-O-α-rhamnopyranosyl-(1→2)-α-arabinopyranosylmesembryanthemoidigenic acid 28-O-α-rhamnopyranosyl-(1→4)-β-glucopyranosyl-(1→6)-β-glucopyranosyl ester; 4, 3-O-α-arabinopyranosylmesembryanthemoidigenic acid 28-O-α-rhamnopyranosyl-(1→4)-6-O-acetyl-β-glucopyranosyl-(1→6)-β-glucopyranosyl ester; 5, 3-O-β-glucopyranosyl-(1→2)-α-arabinopyranosylmesembryanthemoidigenic acid 28-O-α-rhamnopyranosyl-(1→4)-6-O-acetyl-β-glucopyranosyl-(1→6)-β-glucopyanosyl ester.

Some Pharmaceutical Properties of 3-Hydroxypropyl- and 2, 3-Dihydroxypropyl-β-cyclodextrins and Their Solubilizing and Stabilizing Abilities

Abstract: 3-Hydroxypropyl- and 2,3-dihydroxypropyl-beta-cyclodextrins (3-HP- and DHP-beta-CyDs) with different degrees of substitution (D.S.) were prepared and their pharmaceutical properties were investigated. The aqueous solubility of 3-HP- and DHP-beta-CyDs was much higher than that of the parent beta-CyD and the dissolution of DHP-beta-CyD in water was endothermic. The acid- and alpha-amylase-catalyzed hydrolysis rates of 3-HP- and DHP-beta-CyDs were slower than those of the parent beta-CyD. The hemolytic activity (human erythrocytes) and local irritancy (rabbit muscle) of DHP-beta-CyD were considerably less than those of natural, methylated or other hydroxyalkylated beta-CyDs, and decreased with increasing D.S. The ability of the hydroxyalkylated beta-CyDs to remove cholesterol and proteins from human erythrocytes decreased with increasing D.S., and correlated well with their hemolytic activity. 3-HP-beta-CyD was a more effective solubilizer for poorly water-soluble drugs than the parent beta-CyD, and its stabilizing effect on chemically instable drugs was higher than that of the parent beta-CyD. The above data suggest a considerable pharmaceutical potential of 3-HP- and DHP-beta-CyDs as parenteral carriers.

Structures of Fructigenines A and B, New Alkaloids Isolated from Penicillium fructigenum TAKEUCHI

Abstract: Two alkaloids, fructigenines A (1) and B (2), have been isolated from Penicillium, fructigenum TAKEUCHI and the structures were established on the basis of spectroscopic evidence and chemical transformations.