Enhanced dissolution and oral bioavailability of α-tocopheryl esters by dimethyl-β-cyclodextrin complexation

Inclusion complexation of heptakis (2,6-di-O-methyl)--cyclodextrin (DM--CyD) with -tocopheryl acetate and -tocopheryl nicotinate in aqueous solution was studied by the solubility method. The aqueous solubilities of the esters were about 10⁵ times increased by DM--CyD complexation. The phase-solubility diagram of the tocopheryl ester-DM--CyD systems showed a typicalA _p type, and the stability constants (K) of high-order complexes were estimated by analyzing the upward curvature of the diagrams. The solid complex of -tocopheryl nicotinate with DM--CyD in a molar ratio of 12 was prepared by the kneading method. The dissolution rate of the solid complex was much greater than that of the drug itself, and the rapidly dissolving form of -tocopheryl nicotinate, as an example, showed a markedly increased bioavailability (about 70-fold) after oral administration to fasted dogs.     

Determination of the Association Constant of 6-Thiopurine and Chitosan Grafted β-Cyclodextrin

The equilibrium constants (K) for the inclusion complex formationof -cyclodextrin (-CD) with Methyl Orange (MO) and substituted azoanilinium chlorides were determinedspectrophotometrically. Based on the results, the substituent effecton the inclusion complexation of -CD with azoanilinium chlorides was discussed indetail. Further, the solvent effects on the inclusion complexation of MO with -CD andheptakis(2,6-di-O-methyl)--cyclodextrin (DM--CD) wereexamined in aqueous organic mixtures with water-miscible organic compounds(dimethylsulfoxide, acetonitrile, N,N-dimethylformamide, and acetone). It was found that the K value for the inclusion complexformation with -CD and DM--CD decreases remarkably with increasing ratioof organic solvents, dependent of the surface tension of solvent mixtures.     

Mass spectrometric study of monoalkyl-substituted thiacyclanes

Monosubstituted - and -alkylthiophans and -, -, and -alkylthiacyclohexanes were subjected to a comparative mass spectrometric study. The stability of the M⁺ ion increases on passing from - to -alkylthiophans and from - to - and -alkylthiacyclohexanes. In the case of -alkylthiophans and - and -alkylthia-cyclohexanes the principal process is associated with ejection of the substituent as a whole, whereas a portion of the alkyl substituent, with retention of one CH₂ group in the composition of the charged fragment, is eliminated from the molecular ions of -alkylthiophans and -alkylthiacyclohexanes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 176–181, February, 1978.     

Effects of Cyclodextrins on Deodoration of ``Aging Odor'

Hexenal, octenal and nonenal are known causes of unpleasant body odor and are present at markedly increased levels in the middle-aged and elderly. The odor of such unsaturated aldehydes is therefore called ``aging odor'. The present study investigated the effects of cyclodextrins (CDs) on deodoration of crotonaldehyde, pentenal, hexenal, heptenal, octenal, nonenal, decenal, undecenal and dodecenal. -, - and -CD formed inclusion complexes with the majority of unsaturated aldehydes in aqueous solution. The -CD inclusion complex contained the highest amount of guest molecule. One molecule of -CD was estimated to include 1 molecule of short chain aldehyde and 2 molecules of long chain aldehyde. Deodorant testing was conducted by headspace gas analysis using sealed vials. All CDs decreased the concentrations of unsaturated aldehyde. With nonenal, the deodorant power of parent CDs was -CD > -CD > -CD, and that of chemically modified CD was Me-CD > HP-CD > G2-CD > MCT-CD. CDs were demonstrated to reduce ``aging odor'. Me-CD was the most effective type of CD for the deodoration of ``aging odor'.     

Transformations of solasodine

Solasodine (I) has been subjected to a number of transformations. The following compounds have been obtained from it by described procedures: 3-acetoxypregna-5,16-dien-20-one (II), 3-acetoxypregn-5-en-20-ol (III), and 3-acetoxypregn-5-en-20-ol (IV). The oxidation of (III) and (IV), the formation of an oxime, and the reduction of the oxime with sodium in ethanol, followed by Hess methylation, has led to 20-dimethylaminopregn-5-en-3-ol (IX) and to 20-dimethylaminopregn-5-en-3-ol (X). From compounds (IX) and (X), by analogy with (III) and (IV) by their oxidation and the preparation of oximes, which were then reduced and methylated, the following were obtained: 3,20-bisdimethylaminopregnane (XVII) and 3,20-bisdimethylaminopregnane (XVIII), and also quaternary salts of the latter.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 370–374, May–June, 1980.     

Sterol glycosides from the Far Eastern holothurianCucumaria japonica

Sterol -D-xylopyranosides and arabinopyranosides in a ratio of 9:1 have been isolated from a lipid extract of the musculocutaneous sac of the Far Eastern holothurianC. japonica. The main components of both glycosidic fractions were identified as derivatives of cholesta-7,22-diene-3-ol, cholest-22-en-3-ol, 5-cholestan-3-ol, 24-ethylcholesta-7,22-dien-3-ol, and 24-methylene-, 24-methyl-, and 24-ethyl-cholest-22-en-3-ols.Institute of Immunology, Ministry of Health of the USSR, Moscow. M. M. Shemyakin Institute of Biorganic Chemistry, Academy of Sciences of the USSR, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 54, pp. 615–620, September–October, 1984.     

Synthesis of 4,5-Seco-Derivatives of Allobetulin

4,5-Seco-19,28-epoxy-18-olean-3,5-dione wasprepared by ozonation of 19,28-epoxy-18-olean-3(5)-ene. The structures of the synthesized compounds were confirmed using spectral data.     

Inhibitory Effect of Cyclodextrins on the Discoloration Reaction of an Anthocyanidin, Pelargonidin Chloride, in Acidic Media

An anthocyanidin, pelargonidin (PG), loses its color with time in acidic media. The rate determining step of the discoloration reaction at pH 1–4 is the nucleophilic attack of the OH^- ion on PG to give a hemiacetal, which readily isomerizes to the corresponding -diketone. Native, branched, and methylated cyclodextrins (CDs) form inclusion complexes with PG to retard the discoloration. The inhibitory effect (copigmentation) of CDs on the PG discoloration is slight in -CD, significant in - and -CDs, and the largest in heptakis(2,6-dimethyl)--CD (DM--CD). The -CD and DM--CD include the phenyl moiety of PG, whereas -CD includes the benzopyrylium moiety of PG. The CD cavities protect the reaction site of included PG from the attack of the OH^- ion.     

1-Aryl-6-azauracile, 5. Mitt.: Die Synthese von 1-(β-Pyridyl)-6-azauracil-5-carbonsäure und einiger ihrer Derivate

Zusammenfassung Analog wie in vorherigen Mitteilungen^1–4 wurden -Pyridyl-hydrazono-cyanacetylcarbamidsäureäthylester (1), 1-(-Pyridyl)-5-cyan-6-azauracil (2), 1-(-Pyridyl)-6-azauracil-5-carbonsäure (3), deren Thioamid (4), und Amidoxim (5), welches in 1-(-Pyridyl)-5-[5-methyl-1,2,4-oxdiazolyl(3)]-6-azauracil (6) überge-führt wurde, hergestellt.

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-Pyridylhydrazono-cyanacetylcarbamic acid ethyl ester (1), l-(-pyridyl)-5-cyano-6-azauracil (2), 1-(-pyridyl)-6-azauracil-5-carboxylic acid (3), its thioamide (4) and amidoxime (5) were prepared as described in preceding communications. (5) was converted into l-(-pyridyl)-5-[5-methyl-1,2,4-oxdiazolyl(3)]-6-azauracil (6).

     

Polyhydroxysteroids from the Far-Eastern starfishCtenodiscus crispatus

Four new polyhydroxysteroids, 5-cholesta-3,5,6,15,16,25,26-heptaol, 24-ethyl-5-cholesta-3,5,6,15,28,29-heptaol-29-sulfate, (22E)-24-methyl-5-cholest-22-ene-3,5,6,15,25,26-hexaol-26-sulfate, 24-propyl-5-cholesta-3,5,6,8,15,28,29-heptaol, and the known 5-cholesta-3,5,6,15,16,26-hexaol, have been isolated from the starfishCtenodiscus crispatus.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1821–1825, October, 1994.     

Radiation-induced reactions of cholesterol in an aqueous medium

⁶⁰Co -ray radiolysis of cholesterol /3-hydroxy-5-cholestene/ /I/ in the two-phase system /water-ethyl acetate/ and in the presence of air has been studied using TLC and GC methods. The following products were observed in the irradiated mixture: 3, 7-dihydroxy-5-cholestene /II/, G O. 36, 3-hydroxy-7-keto-5-cholestene /III/, G 1.48, 3-hydroxy-7-keto-5-cholestane /IV/, G 0.22, 3,5,6-trihydroxy-5-cholestane /V/, G 0.83, 5,6-epoxy-3-hydroxy-5-cholestane /VIa/, G 0.26, 5,6-epoxy-3-hydroxy-5-cholestane /VIb/, G 0.24, and 2, 3-dihydroxy-5-cholestene /VII/, G 0.22. The dose dependence of the formation of these products shows that the cholesterol derivatives substituted in the position 7 /II–IV/ are formed from a common precursor — the radical Ia. On the other hand, the products of the 5–C=C double bond reactions /V and VI/ are formed independently. Also the product VII is formed independently. A reaction scheme that is in agreement with these results is proposed.     

Triterpene glycosides ofSalsola micranthera. I. Structures of salsolosides C and D

New triterpene glycosides — salsolosides C and D — have been isolated from the epigeal part ofSalsola micranthera Botsch. On the basis of chemical transformations and physicochemical measurements, salsoloside C has been assigned the structure of oleanolic acid 28-0--D-glucopyranoside 3-0-[0--D-xylopyranosyl-(1 4)--D-glucuropyranoside], and salsoloside D has the structure of hederagenin 28-0--D-glucopyranoside 3-0-[0--D-xylopyranosyl-(1 4)--D-glucuropyranoside].Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 727–732, November–December, 1983.     

<Superscript>1</Superscript>H and <Superscript>13</Superscript>C NMR spectra of some drimanic sesquiterpenoids

One- and two-dimensional homo- and heteronuclear correlation proton, carbon, proton—proton, and proton—carbon NMR spectra of fifteen drimanic sesquiterpenoids: 11,12-dibromodrima-5,8-dien-7-one, drim-8-en-7-one, 11-hydroxydrim-8-en-7-one, 11,12-dihydroxydrim-8-en-7-one, 11-hydroxy-11,12-epoxydrim-8-en-7-one, 11-hydroxy-11,12-epoxydrim-8-en-7-one, 8,9-epoxydriman-7-one, 8,9-epoxydriman-7-ol, 11,12-diacetoxydrim-8-en-7-ol, drimane-7,8,11-triol, 7,8-isopropylidenedioxydriman-11-al, 9, 11-dihydroxydrim-7-en-6-one, drimane-7,8,9-triol, drimane-7,8,11-triol, and drim-8-ene-7,11,12-triol were studied. The proton and carbon chemical shifts were assigned.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2589–2594, December, 2004.     

Condensation of 2-(1-ethoxyvinyl)oxiranes with sodiomalonic ester and decarboxylation of the reaction products obtained

-(1-Ethoxyvinyl)- and -(1-ethoxyvinyl)--ethoxycarbonyl--butyrolactones were obtained by the reaction of 2-(1-ethoxyvinyl)oxiranes with sodiomalonic ester. Decarboxylation of the -(1-ethoxyvinyl)--ethoxycarbonyl-butyrolactones in DMSO leads to -(1-ethoxyvinyl)--butyrolactones, the hydrolysis of which gives -acetyl-butyrolactones. Ethyl trans-3-acetyl-3-pentenoate was obtained by decarboxylation of -methyl--(1-ethoxyvinyl)--ethoxycarbonyl--butyrolactone in DMSO.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 22–25, January, 1992.     

Ultrasonic study of the molecular encapsulation and the micellization processes of dodecylethyldimethylammonium bromide-water solutions in the presence of β-cyclodextrin or 2,6-di-o-methyl-β-cyclodextrin

Aqueous solutions of -cyclodextrin (-CD) or 2,6-di-o-methyl--cyclodextrin (DM--CD) and dodecylethyldimethylammonium bromide (D₁₂EDMAB) have been studied from speed of sound (u) data at 298.15 K, using a pulse-echo-overlap technique. The molecular encapsulation process of the surfactant monomer into the cyclodextrin cavity and its effect in the micellization process of the surfactant have been analyzed from theu measurements: I) as a function of [D₁₂EDMAB] in the presence of several initial cyclodextrin concentrations (-CD or.DM--CD); II) as a function of [cyclodextrin] (-CD or DM--CD), for an initial micellar solution of D₁₂EDMAB and; III) as a function of the [cyclodextrin]/[surfactant] stoichiometric concentrations. Both inclusion complexes formed (-CDD₁₂EDMAB) and (DM--CDD₁₂EDMAB) have stoichiometries of 11, and their association constantK have been determined using a model proposed in this work, based on the additivity of the different contributions of the involved species to the speed of sound. The apparent critical micellar concentration, cmc^*, of D₁₂EDMAB is found to increase linearly upon the addition of cyclodextrin (-CD or DM--CD). The free surfactant concentration in the micellar region, [D₁₂EDMAB]_f, decreases in the presence of -CD and slightly increases in the presence of DM--CD. The influence of the parcial methylation of the -cyclodextrin (-CDDM--CD) and of the polar head of the surfactant (D₁₂TAB D₁₂EDMAB) on the complextion and micellar parameters are also discussed.Supplementary material available: Tables of speed of sound (14 pages) are available from the authors.     

In situ crystallization of bacterial cellulose II. Influences of different polymeric additives on the formation of celluloses Iα and Iβ at the early stage of incubation

Effects of polymeric additives with different degrees of polymerization (DP) or substitution (DS) on the crystallization of celluloses I and I have been examined at an early stage of the incubation of Acetobactor xylinum by using newly developed FT-IR spectroscopy. It was found that the mass fraction of cellulose I is greatly decreased with increasing concentrations of carboxymethyl cellulose sodium salt (CMC) or xyloglucan (XG) in the incubation medium. Such a decrease in the mass fraction of cellulose I, which corresponds to the enhanced crystallization of cellulose I, is more prominent for CMC or XG with lower DPs, but the additives with too low DPs are not so effective probably due to higher solubility and the lower adhesion on the surface of microfibrils. Moreover, the mass fractions of celluloses I and I are highly correlated with the crystallite size of microfibrils, indicating that I is crystallized in larger-size microfibrils while I is produced in smaller-size microfibrils. On the basis of these experimental results, the mechanism of the crystallization of celluloses I and I is discussed in the Acetobactor xylinum system.     

Steroid compounds from the starfish Lysastrosoma anthosticta collected in the Sea of Japan

Six polyhydroxylated steroids and their derivatives were isolated from the starfish Lysastrosoma anthosticta collected in the Posyet Bay, Sea of Japan. These include a new glycoside of the steroid polyol, lysastroside A (1), which was identified as (25S)-26-O--d-xylopyranosyl-5-cholestane-3,6,8,15,16,26-hexaol, and the previously known pycnopodioside C monoglycoside (2), marthasterone sulfate (3), (25S)-5-cholestane-3,6,8,15,16,26-hexaol (4), (25S)-5-cholestane-3,6,7,8,15,16,26-heptaol (5), and (25S)-5-cholestane-3,6,7,8,15,16,26-heptaol (6). The compounds were tested for the haemolytic activity and the action on the embryogenesis of the sea urchin Strongylocentrotus intermedius.     

Direction of nucleophilic substitution in α, β-unsaturated imino compounds with a donor substituent in the beta position

A mechanism of conversion of -aminovinyl ketones into -aminovinylimines is disclosed. It has been found that in this and a series of other reactions (various conversions of -aminovinyl ketones, -aminovinylimines, and -alkoxyvinylimino salts and their vinyl analogs, cyano compounds, etc.), the intermediate determining the course of the reaction is an ,-unsaturated imino cation. The result of the reaction depends on the site and efficiency of the nucleophilic attack by tautomeric imino salt compounds possessing an unshared electron pair distributed over the various electrophilic sites of the molecule.     

Steroid glycosides ofNicotiana tabacum seeds I. The structures of nicotianosides A, B, and E

Two steroid glycosides of the spirostan series — nicotianosides A and B — and one glycoside of the furostan series — nicotianoside E — have been isolated from the seeds ofNicotiana tabacum L. Nicotianoside A is (25S)-5-spirostan-3-ol 3-O--D-glucopyranoside, nicotianoside B is (25S)-5-spirostan-3-ol 3-O-[O--L-rhamnopyranosyl-(12)-gb-D-glucopyranoside], and nicotianoside E is (25S)-5-furostan-3,22,26-triol 26-O--glucopyranoside 3-O-[O--L-rhamnopyranosyl-(12)--D-glucopyranoside].Institute of Genetics, Academy of Sciences of the Republic of Moldava, Kishinev, ul. Lesnaya, 20. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 737–742, November–December, 1994.     

Cardenolides of the seeds ofCoronilla glauca and ofC. scorpioides. New glycosides alloglaucoside and scorpiosidol

Two new glycosides have been isolated from the seeds ofCoronilla glauca L. and C. scorpioides Koch: 3-(0-D-glucopyranosyloxy)-14. 15-dihydroxy-19-oxo-5-card-20(22)-enolide (alloglaucoside) and 3-(-D-gluco-ucofuranosyloxy)-5,14,19-trihydroxy-5-card-20(22)-enolide (scorpiosidol), together with a glycoside previously unknown for theCoronilla genus — 3-(-D-glucopyranosylo)g)-14-hydroxy-5-card-20(22)-enolide (desglucouzarin) and known aglycons (corotoxigenin, alloglaucotoxigenin, coroglaucigenin) and glycosides (glucocorotoxigenin, coronillobioside, glucocoroglaucigenin, coronillobiosidol and scorpioside).Ukraine Pharmaceutical Academy, Kharkov–2. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 372–376, May–June, 1996. Original article submitted August 14, 1995.