Solubility Study of Nimodipine Inclusion Complexation with α- and β-Cyclodextrin and some Substituted Cyclodextrins

The solubility of nimodipine was measured in aqueous solutions of the following cyclodextrins: -cyclodextrin (-CD), hydroxypropyl--CD (HP--CD), -cyclodextrin (-CD), random substituted methyl--CD (M--CD), three hydroxypropyl--CDs (HP--CD) with mutually different average degree of substitution, and hydroxypropyl--cyclodextrin (HP--CD). From the determined linear solubility diagrams the values of the binding constant K₁₁ of the inclusion complexes of nimodipine with the respective CDs were evaluated. The -CDs efficiently solubilized sparingly soluble nimodipine, the highest value of K₁₁ was found for M--CD (1680 M^-1), followed by -CD (550 M^-1) and HP--CDs, where the higher degree of substitution lowered K₁₁. Only slight solubilization of nimodipine was observed in the solutions of the -CDs and HP--CD.     

Nitrosation of mefenorex in the presence of cyclodextrins

- and -Cyclodextrin (CD) and heptakis-2,6-di-O-methyl--cyclodextrin (DIMEB) form soluble inclusion compounds with mefenorex (MEF); with -CD a partial inclusion occurs. No solid inclusion compound could be obtained with the four CDs. -, -CD and DIMEB, but not -CD, enhance the nitrosation rate of MEF if the nitrosation assay procedure (NAP test) is applied. During this reaction with - and -CD, solid inclusion compounds of the CDs and nitrosomefenorex (NMEF) precipitate.Part of the Ph.D. thesis of V. Wedelich, Freie Universität Berlin, 1985.     

Selective reduction of the acyl group in cyclic α-acyl-β-dicarbonyl compounds with sodium cyanoborohydride. Efficient synthesis of cyclic α-alkyl-β-dicarbonyl compounds

Efficient synthesis of cyclic -alkyl--dicarbonyl compounds of the cyclopentane, cyclohexane, tetronic acid, and -pyrone series from the corresponding cyclic -acyl--dicarbonyl compounds under the action of NaBH₃(CN) in a THF--HCl system is described.     

Synthesis and thermal decomposition of 3-aroyl-4-aryl-2-pyrazolines

Summary 3-Aroyl-4-aryl-2-pyrazolines (21–40) have been synthesized by the reaction of ,-unsaturated ketones (1–20) with diazomethane. These 2-pyrazolines gave -methyl-,-unsaturated ketones (41–46) on thermal denitrogenation.Dedicated to Prof. Dr.F. Sauter on the occasion of his 65^th birthday     

Bromination of polyfluorinated α,β-enones

Polyfluoroalkyl-,-enones readily add Br₂ to give ,ß-dibromoketones. The latter are readily and regioselectively dehydrobrominated to -bromo-,-enones on treatment with K₂CO₃ or NEt₃ Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2134–2136, December, 1993.     

Ring opening of fluoroalkyl-containing α,β-epoxyketones by aromatic amines

Aromatic amines cause ,-epoxyketones containing a -fluoroalkyl group to undergo ring opening at the -position to give -amino--hydroxyketones.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 882–883, May, 1994.     

Structural analysis of the KGD sequence loop of barbourin, an αIIbβ3-specific disintegrin

Disintegrins constitute a class of small proteins that inhibit platelet aggregation by binding to the fibrinogen receptor, also referred to as integrin _IIb3. Contrarily to other disintegrins that bind to a series of integrins via their Arg-Gly-Asp domain, the recognition site of barbourin contains a Lys-Gly-Asp sequence that ensures its specificity towards _IIb3. In this article, a three-dimensional model of barbourin is proposed using homology modeling and large-scale molecular dynamics simulations. The conformations of the Lys-Gly-Asp sequence of barbourin are analyzed and compared to those of peptidomimetics that exhibit similar specificity towards _IIb3. The tryptophan residue following the Lys-Gly-Asp sequence of the binding domain is shown to play a crucial role in the biological activity and the specificity of barbourin. Our results suggest that this disintegrin anchors to the binding pocket of the -chain of fibrinogen rather than to those of the Arg-Gly-Asp sequence.     

Complex formation of some nonionic surfactants with hydroxypropyl-β-cyclodextrin and with heptakis (2,6-di-O-methyl)-β-cyclodextrin

The interaction of six nonionic surfactants -[4-(1,1,3,3-tetra-methylbutyl)phenyl]--hydroxypoly(oxy-1,2-ethanediyl) with hydroxypropyl--cyclodextrin (HPCD) and dimethyl--cyclodextrin (DIMEB) was studied by reversed-phase thin-layer chromatography in the presence and absence of sodium chloride. Each surfactant formed complexes with both cyclodextrin derivatives; however, the strength of interaction varied considerably. DIMEB formed more stable inclusion complexes with the surfactants than did HPCD. A longer ethyleneoxide chain decreased the strength of interaction, whereas sodium chloride exerted a negligible impact. Principal component analysis indicated that both the hydrophobicity and the specific hydrophobic surface are of the surfactant influenced the complex formation indicating the hydrophobic character of the interaction.Dedicated to Professor József Szejtli.     

Sulfur heterocycles. 13. Oxidative chlorination of β-thiolactones. A novel synthesis of β-(chlorosulfinyl)alkanoyl chlorides and 1,2-oxathiolan-5-one 2-oxides

Chlorination of -thiolactones with chlorine or sulfuryl chloride in acetic anhydride at a reactant ratio (RR) of 1:2:1 gives -(chlorosulfinyl)alkanoyl chlorides in 75–89% yields. Oxidative chlorination of -thiolactones with RR of 1:3:2 affords -(chlorosulfinyl)alkanoyl chlorides and cyclic sulfinic anhydrides (1,2-oxathiolan-5-one 2-oxides). The optimum RR for the preparation of 1,2-oxathiolan-5-one 2-oxides is 1:2:2. Hydrolysis of -chloro--(chlorosulfinyl)carbonyl chlorides has given novel -chlorinated sulfinocarboxylic acids.For communication 12, see [1].A. N. Nesmeyanov Institute of Heteroorganic Chemistry, Russian Academy of Sciences, 117813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 9, pp. 2153–2158, September, 1992.     

Transformed steroids

A preparative method for 9a-hydroxylation of ⁵-3-hydroxysteroids using the fungi ofCircinella sp. 10Kh-1220 not capable of modifying theA ring has been developed. It is established that the yields of the main and the side products greatly depend on the transformation conditions, mycelium age, and the structure of the steroid substrate. Under the optimal transformation conditions novel 9-hydroxysubstituted derivatives of androstenolone, pregnenolone, 16-dehydro-16,17-epoxy-, and-16-methoxypregnenolone have been obtained in 36–80 % yields.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 737–743, April, 1994.     

Substituierte 3-Amino-thiophene und 3-Amino-selenophene aus β-Chlor-α-cyan-zimtsäurenitril

Summary -Chloro--cyano-cinnamonitrile (1) reacts in one step with -oxo-thioles3 or successively with sodium sulphide and -chlorocarbonyl compounds4 to form the 5-substituted 4-amino-2-phenyl-thiophene-3-carbonitriles5. Analogously, the successive reactions of -chloro cinnamonitrile1 with sodium selenide — produced in situ from selene and sodium boronhydride — and -chlorocarbonyl compounds4 yields the 5-substituted 4-amino-2-phenyl-selenophene-3-carbonitriles6.

     

Fluoroaliphatic esters of fluorosulfonic acid. 6. Interaction of fluorine-containing α,β-bis-fluorosulfatocarbonyl compounds with nucleophilic reagents

Fluorine-containing ,-fluorosulfatocarbonyl compounds interact with halides of alkali metals with the formation of -halogeno--dicarbonyl derivatives.A. N. Nesmeyanov Institute of Heteroorganic Compounds, Russian Academy of Sciences, 177813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 3, pp. 715–719, March, 1992.     

Complex Formation Between Alkane-α,ω-Diols and Cyclodextrins Studied by Partial Molar Volume and Compressibility Measurements

The binding of a series of alkane-,-diols, HO(CH₂)_nOH, n = 4 to 7, to - and -cyclodextrin (CD) has been studied by measurements of partial molar volumes (PMVs) and isentropic partial molar compressibilities (PMCs) at 25°C. From the PMV and PMC data, changes in the partial molar quantities upon going from a free state in aqueous solution to a complexed state were evaluated for the diols. Negative changes in PMV and PMC were observed for complex formation with -CD, while positive values were obtained for the -CD complexes. Equilibrium constants for the different complexes, assuming the formation of 1:1 complexes, were evaluated from the PMV and/or PMC data, and were found to increase with increasing chain length of the included diol for both - and -CD complexes. The equilibrium constant for complex formation is generally higher for the -CD than for the -CD complexes.     

α-Alkoxy-β-dicarbonylverbindungen durch Acylierung von Lithiumenolaten

A series of -alkoxy--dicarbonyl compounds2 were prepared by acylation of lithium enolates in good to excellent yields by a simple one-pot procedure.

     

Certain Transformations of Anabasine and Nicotine

Electrocatalytic reduction of the alkaloids anabasine and nicotine was investigated. 1-,-Dipiperidyl and hexahydronicotine were prepared. The reactions of anabasine and the hydrogenated alkaloids with dicarboxylic acid anhydrides were studied.     

Interaction of polyfluoroalkyl-containing aziridinyl ketones with hydrogen halides

Polyfluoroalkyl-containing aziridinyl ketones, unlike their nonfluorinated analogs, react with hydrogen halides to give only -halo- -anvnoketones or their hydrogen halide salts. Thermal decomposition of the latter in the case where Hal = CI affords -chlorovinyl ketones.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 684–686, March, 1996.     

Optimization of mobile phases for HPLC of cis-trans carotene isomers

Summary Various methanol-based, binary and ternary solvent systems were compared with respect to resolution of cis isomers of and -carotene by reversed-phase HPLC. A ternary system: acetonitrile-methanol-methylene chloride (751510), or a binary system: acetonitrilemethanol (9010 or 595) provided the best separation of -carotene and its four cis isomers, 9-cis, 13-cis, 15-cis and 13,15-di-cis--carotene. The elution order of 9-cis and 13-cis--carotene was dependent on the methanol concentration. Methanol-methylene chloride (991) resolved -carotene and its three cis isomers, 9-cis, 13-cis, and 15-cis--carotene. It also proved the best for simultaneous separation of cis isomers of and -carotene. Sample solvent can affect the separation efficiency of each isomer. The presence of cis isomers of and -carotene in fresh and cooked carrots was also determined.     

Reaction of dibenzylphosphine oxide with α,β-unsaturated O-methyloximes

The reaction of dibenzylphosphine oxide with O-methyloximes of some ,-unsaturated ketones results in the phosphorylation at the -carbon atom to form methoxyiminophosphine oxides, whereas the reaction of dibenzylphosphine oxide with O-methyloximes of ,-unsaturated aldehydes affords aminodihydrophosphole oxides.     

Regioselective substitution in α-bromo-β-butoxyvinyl trifluoromethyl ketone by N-nucleophiles

The reaction of -bromo--butoxyvinyl trifluoromethyl ketone with N-nucleophiles proceeds regiospecifically to give amino enones of the push-pull type.     

Silver ion spray reagent for the discrimination of β- and ε-end groups in carotenoids on thin-layer chromatograms

Summary Thin-layer chromatograms of pure carotenoids and natural carotenoid mixtures were dried and sprayed with saturated methanolic silver nitrate solution. Those carotenoids containing -end groups showed a marked bathchromic colour change for each such end group. Thus, -carotene, -cryptoxanthin and zeaxanthin gave a clear red colour while -carotene, -cryptoxanthin and lutein gave deep organge spots after such treatment. Taraxanthin and antheraxanthin could be similarly distinguished. The method was not applicable to paper chromatography.