Comparison of Separation Efficiency of Macrocyclic Glycopeptide-Based Chiral Stationary Phases for the LC Enantioseparation of β-Amino Acids

Direct reversed-phase high-performance liquid chromatographic methods were developed for the separation of enantiomers of eighteen unnatural β-amino acids, including several β-3-homo-amino acids. The direct separations of the underivatized analytes were performed on chiral stationary phases containing macrocyclic glycopeptide antibiotics such as teicoplanin (Chirobiotic T and T2), teicoplanin aglycone (Chirobiotic TAG), vancomycin (Chirobiotic V and V2), and ristocetin A (Chirobiotic R) as chiral selectors. The effects of the organic modifier, mobile phase composition and pH on the separations were investigated. A comparison of the separation performances of the macrocyclic glycopeptide stationary phases revealed that the Chirobiotic T2 column exhibited better selectivity than the Chirobiotic T column for the separation of β-3-homo-amino acid enantiomers; vancomycin or ristocetin A exhibited lower selectivity. The elution sequence was determined in some cases: the S enantiomers eluted before the R enantiomers, with the exception of the Chirobiotic R column, where the elution sequence R < S was observed.     

Reaction of β-Cyclodextrin with N-2,3-Epoxypropylphthalimide. Preparation, Characterisation and Study of a New Substituted Cycloheptaamylose. Effects on the Water Solubility of Drugs

The reaction of -cyclodextrinwith N-2,3-epoxypropylphthalimide yielded a set of newamorphous host compounds with high solubility whichwas transmitted to the corresponding host-guestcomplexes. The structure was determined by comparing the 1H- and 13C-NMR spectra with those of theparent compound, the degree of substitution by integration of the corresponding NMR signals, and C, H,and N elemental analysis.     

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.     

NMR Investigations of the Inclusion of Thyroxine and Derivatives in Natural Cyclodextrins

Thyroxine T4 and its derivatives (T3, T2) are very sparingly soluble in aqueous solutions even in the form of salts. In the presence of or -cyclodextrins and in buffered basic solution, their solubilities are increased by inclusion in the cavity. The inclusion of these hormones in cyclodextrins was investigated by 1H-NMR in order to derive the influence of the number and position of the iodine atoms, and of the ionization state of the phenol group on the inclusion geometries.     

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.     

Simultaneous determination of tetrahydro-β-carbolines and β-carbolines

Summary Reversed-phase ion-pair HPLC with fluorimetric detectors connected in series was studied for the simultaneous determination of two tetrahydro--carbolines and two -carbolines. After additon of internal standards the samples were reacted with fluorescamine, and then subjected to serial extractions to remove their precursor (tryptamine) from the analytical system. This treatment not only suppressed the artefactual formation of tetrahydro--carbolines and -carbolines during analysis, but also effectively purified them. Under optimum conditions, using trifluoroacetic acid as counter ion, all analytes were separated within 14 min and without major interfering peaks. The quantitative ranges were 0.25–80.0 ng mL^–1 for both tetrahydro--carbolines and 0.1–30.0 ng mL^–1 for both -carbolines. Replicate spiking experiments showed that recovery from most of the samples tested was over 90% and the relative standard deviation ranged from 0.7 to 10.4% within and between assays. The proposed method was applicable to various materials such as soy sauce, vinegar, ketchup, tabasco, beer, wine, sake, whisky, brandy, cows' milk, coffee, cocoa, cheese, cigarette smoke and urine.     

A Novel Method to Obtain a β-Cyclodextrin Inclusion Compound by Solid State Reaction: the Ketoprofen Case Revisited

The ketoprofen/beta-cyclodextrin (-CD) inclusion compounds may be conveniently obtained through a solid state reaction at room temperature in the presence of saturated water vapour. Relative to the corresponding complexes produced with the usual coprecipitation method, the new compounds have a higher ketoprofen content and/or different properties. In particular, the formation reaction is not accompanied by a loss of hydration water, which is released in distinct stages upon heating. The thermodynamics of the dehydration process is discussed.     

β-Naphthoquinone sulfonate as electrochemical labelling reagent for high-sensitivity LC analysis of drugs in biological fluids

Summary A new sensitive, high-performance liquid chromatography (HPLC) method using electrochemical detection (ECD) is reported for the determination of 21 amphetamine-like compounds such as amphetamine, methamphetamine, methoxyphenamine, phentermine, ephedrine, mescaline, STP and methylenedioxyamphetamine, in biological fluids. Primary and secondary amines in biological specimens were easily labelled with -naphtho-quinone-4-sulfonate (BNQS) at 60°C for 30 min. Hydrodynamic voltamograms of BNQ-derivatives showed a maximum response at an applied potential of around zero V (against Ag/AgCl) in reducing model. BNQ derivatives of amines were analyzed by HPLC using a reducing ECD at zero V (Ag/AgCl). Separation was on a Bondasphere C18 with mobile phase: acetonitrile-methanol-0.01 M H₂SO₄. Good separations of twenty one amphetamine-analogs were obtained. Only 50 l of biological fluid containing those drugs at a concentration of over 1 g ml^–1 were needed direct for determination with good accuracy. When extraction was carried out prior to the labelling reaction, the detection limits were much improved to less than 10 ng ml^–1.This method was successfully applied to determination of methamphetamine in hair.     

Chiral separation of β-amino alcohols by capillary electrophoresis using cyclodextrins as buffer additives. I. Effect of varying operating parameters

Summary Capillary electrophoresis has been used for the chiral analysis of two -amino alcohol pharmaceutical compounds. Capillary zone electrophoresis conditions were used with -cyclodextrin as a chiral mobile phase additive. The effects of variation of -cyclodextrin concentration, temperature, pH, background electrolyte composition and concentration have been investigated. Optimum separations were achieved for clenbuterol using -cyclodextrin at its solubility limit (16mM), the lowest practicable temperature (19°C), pH 4.0 and an electrolyte solution with a high ionic strength prepared from 0.1 M citric acid and 0.3 M Na₂HPO₄. For the development compound picumeterol and its (S)-enationmer, the optimum pH 4.0 buffer was prepared from 0.1 M citric acid and 0.2 M sodium acetate. Baseline separation with resolution greater than 2 was achieved for both compounds.This work was presented in part at the 2nd International Symposium on Chiral Discrimination, Rome, May 27–31, 1991.     

Determination of the equilibrium melting point of the β-form of polypropylene

The melting behavior of the -form of isotactic polypropylene (-iPP) was investigated as a function of crystallization time and temperature. Calcium suberate, a selective -nucleating agent was used to produce samples that consist entirely of -form i-PP. The experimental melting points were recorded at different crystallization times and were extrapolated to the start of the crystallization process in order to eliminate the effect of lamellar thickening. Using the non-linear Hoffman—Weeks approach to correlate these extrapolated experimental melting temperatures with the corresponding crystallization temperatures, an equilibrium melting point of 209°C was obtained for -iPP. The equilibrium melting point estimated through the non-linear Hoffman—Weeks analysis is about 30°C higher than that (T _m ⁰=177°C) obtained on the basis of the linear extrapolation. These results are consistent with earlier claims that a linear extrapolation of T _m–T _c data leads to an underestimation of the equilibrium melting point. The results obtained for -iPP exemplify the importance of accounting for both the isothermal lamellar thickening effects and the non-linearity in the T _m–T _c correlation, when the determination of an equilibrium melting point is carried out using a procedure based on the predictions of the Lauritzen—Hoffman secondary nucleation theory.This revised version was published online in November 2005 with corrections to the Cover Date.     

Conformation Analysis of Ile-Ala-Val-Pro Peptide and Its Derivatives by Circular Dichroism

Ile-Ala-Val-Pro as a hypocholesterolemic peptide was isolated from soybean protein. We have synthesized four peptides, Ile-Ala-Val-Pro-Gly-Glu-Val-Ala, Leu-Ile-Ala-Val-Pro-Gly-Glu-Val-Ala, Ile-Ala-Val-Pro-Thr-Gly-Val-Ala, Leu-Ile-Ala-Val-Pro-Thr-Gly-Val-Ala, with a conserved Ile-Ala-Val-Pro amino acid sequence, for circular dichroism investigations. These four peptide sequences were also found in the amino acid sequence in soybean protein, which was defined from the genomic sequence. Additionally for a detailed analysis of conformation features of these peptides, the Ile-Ala-Val-Pro and Leu-Ile-Ala-Val-Pro were also synthesized. All peptides were prepared using standard fluorenylmethyloxycarbonyl methodology and the peptide yields ranged from 90 to 95% of the theoretical yields with purity after purification above 99%.     

Polycarboxylated Derivatives of b.beta;-Cyclodextrin

The synthesis of polycarboxylated derivatives of -cyclodextrin obtained by reacting maleic anhydride and suitable thiolic compounds is described. The derivatives were characterised by potentiometric analyses and ¹³C-NMR spectra. The products obtained show a great solubility in water, but also in ethanol and methanol and act as complexing agents for many bivalent metallic cations. These derivatives are probably biodegradable and non toxic.     

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     

Polynuclear hydroxy-bridged Structure in metallo-β-cyclodextrin complexes: A study of magnetic susceptibility versus temperature

Data of the variation of magnetic susceptibility with temperature were obtained by the Gouy balance method for a series of metallo-/-CD complexes. The results support the proposal for the presence of polynuclear hydroxy-bridged structures with interacting paramagnetic centres giving rise to an antiferromagnetic character for these complexes. In the case of the Cu(II) complex estimates of the Cu-Cu distance and the Cu-O-Cu bond angle were obtained from the data.     

Metal Ion Guest Responsive Benzoxazine Dimers and Inclusion Phenomena of Cyclic Derivatives

This study was carried out with the aim to optimize the dissolution propertiesof diclofenac (DIC) – a non-steroidal anti-inflammatory drug sparingly solublein water – through association -with -cyclodextrin (CD). Theeffect of CD on the aqueous solubility of DIC was evaluated by thephase solubility method. The amount of DIC dissolved increased linearly withthe addition of CD according to an AL type plot and without precipitationof the complex. The apparent stability constant of the complex, calculated supposinga 1:1 stoichiometry, was 295 M^-1; this value was confirmed by circulardichroism analysis. DIC/CD interactions were also studied in water by¹H and ¹³C NMR spectroscopy. Equimolar DIC/CD solid systems were prepared by physical-mixing, kneading, co-evaporation andfreeze-drying, and their properties in the solid state studied by DifferentialScanning Calorimetry, X-ray powder diffractometry and Fourier-TransformInfrared analysis. For sake of comparison, the mixture of DIC and CDseparately lyophilized was investigated too. The results demonstrated that thefreeze-dried product had the highest degree of amorphization and they were inagreement with the existence of an inclusion complex in the solid state. Thedissolution profiles of the drug from each solid system were affected by its physico-chemical properties, the freeze-dried being the most rapidly dissolvingforms.     

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.     

Application of β-cyclodextrin for the analysis of estrogenic steroids in human urine by high-performance liquid chromatography

Summary A procedure is described for simultaneous determination of estriol, estrone and 17-estradiol in human urine. After acid hydrolysis of the sulphate conjugates, the estrogens were extracted into diethyl ether. The ether extracts were concentrated and applied directly to an HPLC column. Using a 25 cm C-18 column and acetonitrile-water modified by the addition of -cyclodextrin as mobile phase, the separation of estriol, estradiol and estrone was achieved within 20 minutes. The extraction of estrogens from the biological matrix is excellent. Estrogens were detected using a UV-detector (280 nm) or a spectrofluorimetric detector (_exc=280nm, _em=312 nm). The latter detection system has been used for the determination of estrogens in the urine of non-pregnant women. The procedure is simple and can be used in clinical practice.     

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.     

Preferential inclusion of food colours via formation of their inclusion complexes withβ-cyclodextrin (β-CD)

The encapsulation of commercially utilized food colours with-cyclodextrin is reported. Thus, inclusion complexes of Sunset Yellow, Amaranth, Ponceau 4R, Carmoisine, Fast Red E, Tartrazine and Erythrosine with-CD were prepared. The formation of inclusion complexes was established by, among other methods, UV, reflectance and X-ray diffraction techniques. The host-to-guest ratio was determined by a UV spectral method. The effect of inclusion with-CD on binary mixtures such as Raspberry Red, Tomato Red and Orange Red was also studied.     

Reactions with β-cyanoethylhydrazine,III. A new approach for the synthesis of substituted 3,5-diaminopyrazole and 1,2,4-triazoles

The reactivity of -cyanoethylhydrazine toward enaminonitrile and aroyl isothiocyanates is reported. A variety of 3,5-diaminopyrazole and ³-1,2,4-triazolin-5-thione derivatives could be prepared.

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Reaktionen mit -Canyethylhydrazin, 3. Mitt.: Ein neuer Weg zur Synthese von substituierten 3,5-Diaminopyrazolen und 1,2,4-Triazolen

Zusammenfassung Es wird über die Reaktivität von -Cyanethylhydrazin gegenüber Enaminonitril und Aroylisothiocyanaten berichtet. Es konnte eine Reihe von 3,5-Diaminopyrazol-und ³-1,2,4-Triazolin-Derivaten hergestellt werden.