Synthesis ofN-alkylamides of 3-fluoroalkylaziridine-2-carboxylic acids

The N-alkylamides of 3-fluoroalkylaziridine-2-carboxylic acids have been prepared for the first time by the interaction of ethyl 0-fltioroalkyl-,-dibromocarboxylates with primary amines.Prepared by a known procedure;² characteristics of previously unknown ester1b are given in the Experimental section.     

Improvement of Solubility and Dissolution of 19-Norprogesterone via Inclusion Complexation

In an effort to modify the solubility and dissolution rate of the contraceptive steroid, 19-norprogesterone in order to improve its bioavailability, the cyclodextrin complexation approach was chosen. In solution, the complex formation with -cyclodextrin (-CD), hydroxyethyl -cyclodextrin (HE--CD) and hydroxypropyl -cyclodextrin (HP--CD) was confirmed by using solubility, UV, IR and ¹H-NMR spectrophotometric techniques. The phase solubility diagrams were categorized as A_L-type. The complexing affinity of the CDs investigated were ranked as follows: -CD > HP--CD > HE--CD. The complexation thermodynamic parameters were obtained from the temperature dependence of the dissociation constants. In the solid state, differential scanning calorimetery (DSC) and optical microscopy methods were utilized to characterize the complexes. Dissolution studies showed that such molecularly encapsulated forms offered a marked improvement in the dissolution rate compared to the parent drug.     

Synthesis of Ethyl cis- and trans-4-Chloro-5-oxo-1,2-diphenylpyrrolidine-2-carboxylate

Ethyl cis- and trans-4-chloro-5-oxo-1,2-diphenylpyrrolidine-2-carboxylate have been synthesized by the cyclization of ethyl N-(,-dichloropropionyl)-N-phenyl--aminophenylacetate.     

Spectroscopic and quantum chemical investigation of enol-enol tautomerism of 2-acetyltetronic acid

Vibratonal spectra of 2-acetyltetronic acid (ATA) (3-acetyloxolane-2,4-dione) were investigated in different aggregate states.Ab initio quantum chemical calculations (3-21G basis set) of 2-formyltetronic acid as analogue of ATA and semi empirical calculation of ATA were carried out. The tautomeric forms of ATA can be arranged in the following series with respect to thermodynamic stability (in decresing order):1a,1b,2a,2b.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1043–1048, June, 1995.     

Photochemical addition of diethyl ether to β,β,β',β'-tetrakis(trifluoromethyl)divinyl ether

The 1:1 adducts of diethyl and ,,','-tetrakis(trifluoromethyl)divinyl ether (1),i.e., 3,5-(ee)-bis[2,2,2-trifluoro-1-(trifluoromethyl)ethyl]-2,6-dimethyl-1,4-dioxane (2) (3 isomers) and 4-ethoxy-1,1,1-trifluoro-2-trifluoromethyl-3-[3,3,3-trifluoro-2(trifluoromethyl)propenyloxy]pentane (3), have been obtained by UV-irradiation of a solution of divinyl ether1 in diethyl ether. The X-ray structural investigation of the all-(e)-isomer of dioxane (2) has been carried out.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 85–88, January, 1994.     

Synthese von 4-Acetoxy-1-aryl-2-azetidinonen

The 4-carboxy-2-azetidinones1 a,1 b und1 c react with leadtetraacetate/pyridine to give the 4-acetoxy-1-aryl-2-azetidinones2 a, 2 b and2 c. Hydrogenolysis of2 a yields2 d.

     

In vitro Release Study of Tretinoin from Tretinoin/Cyclodextrin Derivative Complexes

The effects of -cyclodextrin, hydroxypropyl -cyclodextrin and dimethyl -cyclodextrin complexes on the in vitro release of tretinoin gels were investigated. The experiments were carried out in a Franz cell using a silicone membrane as a barrier for the diffusion of the vehicle. Two types of vehicle were compared: a hydroalcoholic gel in which both tretinoin and the inclusion complexes are soluble, and an aqueous gel in which only the complexes are soluble but tretinoin is dispersed. As expected, the release rate of free tretinoin in the hydroalcoholic gel is much faster than in the aqueous gel. However, with the aqueous gel, the cyclodextrin complexation enhances the diffusion rate of the active drug through the membrane, especially with the hydroxypropyl cyclodextrin inclusion compound. The release of tretinoin is related not only to the stability constant of the inclusion, but also to the binding properties of the inclusion compounds to the vehicle.     

Synthesis and biological activity of yuccagenin bisrhamnoside

The two hydroxyls of yuccagenin can be glycosylated by Koenigs-Knorr condensation with acetobromorhammose in dichloroethane in the presence of mercuric cyanide. The bisrhamnoside of yuccagenin markedly lowers the cholesterol and triglyceride content in blood serum of healthy animals and animals with experimental hyperlipidemia.Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 242–243, May–June, 2000.     

Boron chelates with 5,5,5-trifluoro- and 5,5,5-trichloro-4-aminopent-3-en-2-ones

Boron chelates were obtained by the reaction of butoxy(butylthio)diphenylborane with 5,5,5-trifluoro(trichloro)-4-aminopent-3-en-2-one, and their reactions with primary amines were investigated. -Diiminate complexes of boron with trifluoro- and trichloromethyl groups were synthesized.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp. 2657–2661, November, 1992.     

Hetero-Diels-Alder reaction of 3-aryl-2-benzoyl-2-propenenitriles with enol ethers. Synthesis of 2-alkoxy-3,4-dihydro-2H-pyran-5-carbonitriles

Summary The hetero-Diels-Alder reaction of 3-aryl-2-benzoyl-2-propenenitriles1a–d with enol ethers2a–c yieldscis/trans diastereoisomers of 2-alkoxy-4,6-diaryl-3,4-dihydro-2H-pyran-5-carbonitriles3 and4 in 79–98% yield. The similar reaction of1a–c with cyclic enol ether5 affords diastereoisomeric cycloadducts6 and7 withcis annulated pyran rings. Reaction of3 with sulfuric acid leads to 2-hydroxy-3,4-dihydro-2H-pyran-5-carbonitriles8 and9.

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Hetero-Diels-Alder-Reaktion von 3-Aryl-2-benzoyl-2-propennitrilen mit Enolethern. Synthese von 2-Alkoxy-3,4-dihydro-2H-pyran-5-nitrilen

Zusammenfassung Die Hetero-Diels-Alder-Reaktion der 3-Aryl-2-benzoyl-2-propennitrile1a–d mit den Enolethern2a–c ergibt diecis/trans-diastereomeren 2-Alkoxy-4,6-diaryl-3,4-dihydro-2H-pyran-5-nitrile3 und4 in einer Ausbeute von 79–98%. Dieselbe Reaktion von1a–c mit dem cyclischen Enolether5 liefert die diastereomeren Cycloaddukte6 und7 mitcis-anellierten Pyranringen. Reaktion von3 mit Schwefelsäure führt zu den 2-Hydroxy-3,4-dihydro-2H-pyran-5-nitrilen8 und9.

     

Induced circular dichroism spectra of the cyclodextrin complexes with 2-Thioxo-1,3-benzodithiole and 2-Selenoxo-1,3-benzodithiole

The induced circular dichroism (ICD) spectra of -cyclodextrin (-CD) complexes with 2-thioxo-1,3-benzodithiole and 2-selenoxo-1,3-benzodithiole have been measured. From the signs of the ICD spectra of both complexes, the polarization directions for the excited states have been investigated.     

A Simple and Rapid Method of Identification of Extracellular Plant Galactosidases

A simple, rapid, and sensitive procedure for the identification of plant extracellular - and -galactosidase is described using callus cultures of seedlings from the tested plant, roots of 4-6 day old seedlings of Californian poppy germinating on agar plates, and cell suspension cultures cultivated from callus cultures. Synthetic substrates were used for the determination of the intra- and extracellular activities of - and -galactosidase. Many imino- or azasugars are strong glycosidase inhibitors, and some of them show promising chemotherapeutic effects against viral disease and are potential antidiabetic as well as antitumor agents. This fact aroused our interest for a rapid and sensitive assay method of the activity of - and -galactosidases of plant origin. The results presented here show the perspective usefulness of extracellular galactosidases of plant origin in inhibitory and/or biotechnological studies.     

A new method for the synthesis of CF3-containing aminovinyl ketones

A new method for the synthesis of aminovinyl trifluoromethyl ketones was developed. The method is based on the reactions of 4-sulfonyl-1,1,1-trifluorobut-3-ene-2,2-diols with various alkyl-, aryl-, dialkyl-, and alkylarylamines. The stereochemistry of the compounds obtained was studied.     

Struktur/Geruchs-Beziehungen von mit β-Santalol verwandten Verbindungen:E-Homo-β-santalol undE-Dehydrohomo-β-santalol

Summary To study the structure/odour relationships of -santalol analogues two homologous -santalol derivatives5 and6 were synthesized. The key steps thereby were the -alkylation of the bicyclic starting ketones8 and14 accomplished by using more drastic conditions as usual. The odours of5 and6 are described in detail.

Auszugsweise vorgetragen am 19th International Symposium on Essential Oils and Other Substrates, 9. September 1988, Greifensee/Dübendorf, Schweiz     

Reactions of aziridine,its dimer, 2,2-dimethyl-aziridine dimer,and β,β-bis-N-aziridinoethylamine with aromatic aldehydes and dialdehydes

The reactions of aziridine, its dimer, 2,2-dimethylaziridine dimer, and the novel compound ,-bis-N-aziridinoethylamine with aromatic aldehydes and dialdehydes have given novel compounds.N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 117977 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 9, pp. 2131–2137, September, 1992.     

Triterpene Glycosides from Plants of the Astragalus Genus. III. Structure of Cyclounifolioside C from Astragalus unifoliolatus

The known compound cyclocantogenin (1) and a new cycloartane glycoside cyclounifolioside C (2), which has the structure 24R-cycloartan-3,6,16,24,25-pentaol 3-O--D-glucopyranoside, were isolated from roots of Astragalus unifoliolatus Bunge. The structures of the isolated compounds are established using hydrolysis and spectral data.     

Interaction of fluoroalkyl-containing β-diketones with amines

The composition of products of the interaction of asymmetric fluoroalkyl-containing -diketones with amines was studied. Mixtures of regioisomeric -aminovinylketones and products of cleavage and secondary condensation are formed, depending on the temperature, the solvent, the nature of the fluorinated and nonfluorinated substituents in the -diketone, and the basicity of the amine. The major product is a -aminovinylketone in which the NH₂ group is removed from the fluoroalkyl substituent. No -aminovinylimines, products of condensation involving two electrophilic centers, were observed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2278–2284, September, 1996.     

Influence of the Structure of Steroid Hormones on Their Association with Cyclodextrins: A High-Performance Liquid Chromatography Study

The association constants of fourteen steroid hormones with - and -cyclodextrin were measured in methanol-water (20 : 80 v/v) at 35 °C using the chromatographic Hummel-Dreyer method. It was found that the greatest influence on the association constants is the structural features of ring A of these compounds but the substituents of ring D also alter the complex stability to an appreciable degree. The measured association constants were considerably greater than the corresponding values measured previously in the medium containing more methanol (45 instead of 20%).     

Elucidation of a common structure of selective fibrinogen receptor antagonists

In this paper, we investigate the common structural and electrostatic parameters of a series of specific inhibitors of the IIb3 integrin. Molecular dynamics simulations with an explicit aqueous environment led to an original theoretical pattern. Our results may suggest that the studied non-peptide IIb3 antagonists developed upon the Arg-Gly-Asp ubiquitous recognition sequence, in fact, should mimic the C-terminus part of the fibrinogen chain. This assumption could, therefore, explain their specificity with respect to other Arg-Gly-Asp-dependent integrins.     

Alfaxalone: Effect of Temperature on Complexation with 2-Hydroxypropyl-β-cyclodextrin

Phase solubility analysis is used to investigate the complex formation of alfaxalone with various cyclodextrins(2-hydroxypropyl--cyclodextrine [HPBCD],-cyclodextrin [BCD] and2-hydroxypropyl--cyclodextrin [HPGCD]).The complexationwith HPBCD was studied in more detail by looking at the effect of temperature on the stability constants using phase solubility analysis. HPLC-analysis was used to measure the dissolved amount of alfaxalone.The solubility of alfaxalone increases linearly with increasing concentration of cyclodextrin, suggesting the formation of a 1 : 1 complex. For the parent BCD the complex starts precipitating out of solution when the solubilizer concentration exceeds 0.25% making the unsubstituted BCD less useful for the preparation of solutions of alfaxalone. Substituted cyclodextrins do not form insoluble complexes with alfaxalone. The complexation constant for BCD and HPBCD are comparable in magnitude, but for HPGCD, the constant is substantially lower.The effect of temperature on thecomplexation constant was also studied at elevated temperature. Increasing the temperature results in an increased S₀ (solubility without HPBCD) and a decrease in the value of the complexation constant. The net effect results in minor changes of the solubility of alfaxalone as a function of temperature. Based on regression analysis, the change in enthalpy for complex formation between alfaxalone and HPBCD is calculated as -4610 cal/mol.The results indicate that substitutedcyclodextrins are useful in the preparation of solutions of alfaxalone. Since 1 : 1 complexes are formed there is no theoretical danger for precipitation on dilution, e.g., after injection.