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  • Organic Chemistry  (4,530)
  • 1990 - 1994  (4,530)
  • 1
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Calculations were carried out to study the validity of σ-scales for hydrogen abstraction from substituted toluenes by tert-butyl, tert-butoxyl and tert-butylperoxyl radicals. Rate constants were compiled and evaluated from the literature for meta- and/or para-substituted toluenes. The substituents were characterized by factored ionic sigmas (σI, σR, σR+), ionic scales (σ, σ+) and various radical sigmas (σσ). The dependence of log k values on these substituent descriptors was investigated using ‘stepwise linear regression’ and ‘all possible regression’ methods. The following predictive equations can be recommended: for tert-butyl radicals, at 321 K: \documentclass{article}\pagestyle{empty}\begin{document}$$\begin{array}{*{20}c} {\log \,k_1 \, = \,1.024\, + \,0.776\,\sigma _1 \, + \,0.653\,\sigma _{\mathop C\limits^. }} \quad {(R\, = \,0.8137)} \end{array}$$\end{document} for tert-butoxyl radicals, at 313 K: \documentclass{article}\pagestyle{empty}\begin{document}$$\begin{array}{*{20}c} {\log k_2 = 5.529 - 0.623\sigma ^ +} \quad {(R = 0.9376)} \end{array}$$\end{document} and for tert-butylperoxyl radicals, at 303 K: \documentclass{article}\pagestyle{empty}\begin{document}$$\begin{array}{*{20}c} {\log k_3 = - 1.410 - 0.810\sigma + 0.337\sigma _{\mathop C\limits^. } } \quad {(R = 0.9628)}\end{array}$$\end{document} The results suggest that there is no unversal radical scale for hydrogen abstraction reactions, that the rate is primarily influenced by polar factors (inductive, resonance) and that only two radical scales (σĊ and σα·) are appropriate, showing a small, yet significant, role of radical stabilization.
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  • 2
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 7 (1994), S. 256-258 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The relative thermodynamic stabilities of 2-propenylbenzene (allylbenzene), and the E and Z forms of 1-propenylbenzene were determined over the temperature range 50-170°C by chemical equilibration in DMSO solution with t-BuOK as catalyst. The values of the thermodynamic parameters ΔG⊖, ΔH⊖ and ΔS⊖ at 298·15 K for each isomerization reaction between the title compounds were evaluated.
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  • 3
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: According to quantum chemical calculations, the anion radical of disilene adopts a syn- or anti-pyramidal geometry. The former is not a stable entity on the electronic hypersurface and it decreases further in energy by rotation of the Si-Si bond. Energy optimization of various structural alternatives reveals for the anion radical an Si-Si bond slightly longer than a single bond. The anti geometry prefers a C2h geometry whereas the syn geometry resembles a silylene coupled with a silylene radical anion. The fragmentation of disilene into two silylene units is less exothermic for the neutral species than for the anion (radical), as examined by the ab initio calculations.
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  • 4
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: New N-alkylation and N-arylation procedures starting from anilinomagnesium (ArNHMgBr) are reported. For N-alkylation with alkyl bromides, addition of hexamethylphosphoramide to an ArNHMgBr solution in tetrahydrofuran (THF) is effective. After heating at 55°C, N-monoalkylation product was obtained in 60-90% yield, slight dialkylation taking place. The combined use of aryliminodimagnesium [ArN(MgBr)2] with α,ω-dibromoalkanes led to N-arylazacycloalkanes. For N-arylation with iodobenzene, replacement of THF with pyridine and additional use of copper(I) iodide are effective. After heating at 115°C with iodobenzene, mono- and diarylation products were obtained, the former being predominant. The combined use of ArNHMgBr and N,N,N′,N′-tetramethylethylenediamine as the ligand of copper species is effective for elimination of diarylation and other undesired products, and leads to diarylamines in excellent yield. The method is of advantage over the conventional Ullmann and Chapman methods. The polar solvents and copper salt are effective additives for inducing ‘inert combinations’ of ArNHMgBr or ArN(MgBr)2 with alkyl and aryl halides into N—C coupling, to extend the unified view proposed for the reactivity of magnesium reagents. The difference in the roles of N—Mg and N—Cu species is discussed.
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  • 5
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Laser flash photolysis of a series of alklylbromo- and alkylfluorodiazirines in pentane at ambient temperature generates alkylhalocarbenes by decomposition of the diazirine excited states. The halocarbenes can be intercepted with pyridine to form ylides. The ylides absorb intensely between 350 and 400 nm and are fairly long lived (τ » 10 μs), making them convenient probes of the yield and dynamics of the carbene. The yield of the ylides increases with increasing pyridine concentration up to 1·5 M. At pyridine concentrations > 1·5 M the yield of ylide is saturated, signifying that every carbene generated in a laser pulse is captured by pyridine prior to reaction with solvent or intramolecular rearrangement. The yield of trappable carbene generated from alkylbromodiazirines closely tracks the bond dissociation energy of the C—H bond adjacent to the diazirine moiety. The data indicate that the excited states of the alkylbromodiazirines suffer C—H migration (or C—C migration with cyclobutylbromodiazirine) and nitrogen extrusion in competition with carbene formation. The yield of trappable carbene derived from the alkylfluorodiazirines is independent of the bond dissociation energy of the adjacent C—H bond. This is probably a consequence of the great thermodynamic stability of α-fluorocarbenes.
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  • 6
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Reaction of aryliminodimagnesium [ArN(MgBr)2, IDMg] with nitrobenzene (Ar1NO2) in tetrahydrofuran (THF) gives unsymmetrical (unsym) azoxybenzene, which is deoxygenated to give unsym-azobenzene. The reaction is utilized for the independent preparation of ONN and NNO isomers of unsym-azoxy compounds. The effects of the relative value of the difference between oxidation and reduction potentials of para-substituted reactants, special effects of ortho-substituents of the substrate and also effects of structure and concentration of mono- and bis-IDMg reagents were studied previously, and ‘cooperation of their aggregate excess needed for product formation’ was proposed. This unfamiliar concept for reactions of magnesium reagents was studied further. Supporting evidence was obtained from the retarding effect of trimethylene chains of nitro [3.3] metacyclophanes and the derived azoxy [3.3] metacyclophanes and also from the effect of the length of bis-IDMg's central α,ω-polymethylenedioxy chain appropriate for azoxy deoxygenation. By comparison with deoxygenation by X3P reagents (X = EtO, Me2N), the general needs of cooperation of excess magnesium reagents were confirmed and its role in their reactions is discussed.
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  • 7
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The low temperature 1H NMR spectra of 2,2-bis(3,5-dibromomesityl)ethenol in CS2-CD2Cl2 (3:7) display new signals which indicate the presence of four enol species whose OH is hydrogen bonded. Oligomerization to intermolecularly hydrogen-bonded enol dimers or tetramers is suggested.
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  • 8
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Measurements of absorption and emission spectra, fluorescence quantum yields (Φf) and lifetimes (τf) of ω-(1-pyrenyl)alkyl para-substituted benzoates PnX (X = H, Cl, CF3, CN, NO2, with n = 1-4) were carried out in solvents of various polarity. Intramolecular interaction in the ground state is not observed in any of these compounds. PnCN (n = 2-4) shows an intramolecular exciplex emission in solvents of low to high polarity. The broad, structureless emission at longer wavelength observed in ethyl acetate solution of P1CN is ascribed to an ‘exciplex-type’ emission which does not require actual overlapping of the two chromophores. P2CF3 also shows an exciplex emission in solvents of medium to high polarity. The solvent dependence of both Φf and τf increases as the electron-withdrawing ability of the para-sustituents increases. The relationship between fluorescence quenching by electron transfer and para-substituent of PnX is discussed by means of the free energy for electron transfer, ΔGET, obtained from the oxidation and reduction potentials of pyrene and methyl para-substituted benzoates in acetonitrile, respectively. PnH, with positive ΔGET, does not show a solvent dependence of Φf, except for P1H, in which ca 40% of the fluorescence is quenched in acetonitrile. PnCl, with slightly negative ΔGET, shows more efficient quenching, but does not show exciplex emission. PnCN, PnCF3 and PnNO2 have ΔGET values between -0·36 and -0·65 eV, and their fluorescence is fairly efficiently quenched. The fluorescence of PnCN is concluded to be strongly quenched by intersystem crossing from the singlet exciplex to the locally excited pyrene, and by electron transfer from the pyrene part to the benzoate part. That the formation of a singlet exciplex is necessary for intersystem crossing in bichromophoric compounds containing pyrene is thus clearly illustrated.
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  • 9
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Magnetic coupling between two sterically protected phenoxyl radicals through the cis- and trans-stilbene chromophores was studied by means of their EPR fine structures. While the zero-field splitting parameters D, which are governed by the magnitude of dipolar coupling, were dependent on the geometrical isomerism, the sign of exchange coupling was independent of it and dictated by the topology of the π-conjugated systems: ferromagnetic in o,m-isomers and antiferromagnetic in m,m'-isomers.
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  • 10
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The magnitude ρx(ρnuc) is shown to decrease with increase in the extent of bond making estimated by the kinetic isotope effect for the reactions of Y-benzoyl chlorides with anilines, XC6H4NH2, in acetonitrile at 25·0°C.
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  • 11
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The radical cation of N,N′-bis-(4-dimethylaminophenyl)pyridazine (3·+) has a near-IR band with a transition energy of 29·7 ± 0·5 kcal mol-1 (1 kcal = 4·184 kJ) in acetonitrile. This band is assigned to a Hush-type charge-transfer band, and the transition energy to the Marcus λ value for electron transfer. Such a large λ is inconsistent with previous estimates of λ for intermolecular electron transfer between mono-p-phenylenediamines and their radical cations. It agrees well with estimates of λ based on AM1 semi-empirical MO calculations, which gives the enthalpy contribution to λin at about 21 kcal mol-1 for 3·+. It is suggested that the traditional method of estimating λin by summing bond displacements weighted by force constants produces values which are significantly too low for systems such as phenylenediamines, where pyramidalization changes are important. The results suggest that λ for tetramethyl-p-phenylenediamine self-electron transfer (10/·+) has been significantly underestimated, and that this prototype organic electron transfer reaction is not as strongly diabatic as was previously concluded.
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  • 12
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The reaction of nitrosobenzene with aniline, to give azobenzene, in basic conditions was studied. It was shown that the reaction exhibits general base catalysis by different buffers giving a Brønsted coefficient β = 0·318. As in previous studies, a two-step process with a first step of attack of aniline on nitrosobenzene to give an addition intermediate and a second step of dehydration of this intermediate is proposed to interpret the mechanism of the reaction. The analysis of the Brønsted relationship and of the intermediate of the reaction led to the suggestion that hydoxide ion catalyses the reaction by a mechanism of general base catalysis in the dehydration step.
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  • 13
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Protonation of tetrafluoro-2,11-dithia [3·3]paracyclophane and tetrafluoro-2,11-dithia [3·3]metaparacyclophane in high-acidity super acid media, namely FSO3H.SbF5 (1:1) ‘magic acid’-SO2CIF, gave their corresponding acidic disulfonium ions. Additional ring protonation to give a disulfonium-monoarenium trication was not observed. With the non-fluorinated 2,11-dithia [3·3] cyclophanes, the disulfonium ions can be ring protonated in equilibrium to give a dynamic disulfonium-monoarenium trication. Tetrafluoro [2·2]-metaparacyclophane is monoprotonated at the meta ring and gives a complex mixture of conformational isomers. Multinuclear magnetic resonance data on the cyclophane precursors and their derived cations are compared and analysed. The energies, conformations and charge distributions of the isometric fluorinated and non-fluorinated [2·2] - and dithia [3·3] cyclophanes were calculated by the AM1 and PM3 methods, respectively. In all but one case the cyclophane arenium ions predicted by theory to be energetically most favoured are those observed in solution under stable ion conditions. In agreement with experiment, the instabilities of S,S,C-cyclophane trications are also theoretically predicted.
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  • 14
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    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 7 (1994), S. 116-116 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
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  • 15
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
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  • 16
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
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  • 17
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The kinetics of oxidation of metol (N-methyl-p-aminophenol) by thallium(III) have been studied in a perchloric acid medium. This organic compound is employed extensively in photographic work. The stoichiometry of the reaction is represented by: C6H4(OH)NHCH3 + TIIII → C6H4(O)NCH3 + TII + 2H+The kinetics indicate the rate law: \documentclass{article}\pagestyle{empty}\begin{document}$$k' = \frac{{Kk\left[{metal} \right]}}{{1 + K\left[{metal} \right]}}$$\end{document} where k′ is the pseudo-first-order rate constant. The rate constants and thermodynamic parameters for the rate-limiting step have been evaluated.
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  • 18
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Kinetic studies were carried out on the aminolysis of propargly and 1-methylpropargyl arenesulphonates in acetonitrile at 45·0°C. The cross-interaction constants, ρxz and βxz, are similar to, but smaller than, those for the SN2 processes at other primary and secondary carbon centers. Compared with the allyl series, the smaller magnitude of ρxz and βxz reflects a looser transition state, which in turn leads to a lower rate despite the greater Taft's σ* value and the lower intrinsic (ΔE0≠) and thermodynamic barriers (ΔE0).
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  • 19
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Transition structures for the Diels-Alder reactions of 1,3,4-oxadiazole with ethylene, acrylonitrile, maleonitrile, fumaronitrile, and 1,1-dicyanoethylene were located with ab initio molecular orbital calculations with the RHF/3-21G theoretical model. The activation energies were calculated by single-point calculations with the RHF/6-31G* and MP2/6-31G* theory levels on the RHF/3-21G geometries. Geometries of two transition structures and the corresponding reactants were generated at the MP2/6-31G* and the energies evaluated at the MP3/6-31G* level. The values obtained are comparable to those generated by MP2/6-31G*//3-21G. The asynchronicity of the transition structures follow the same trend as the corresponding all-carbon Diels-Alder reactions with buta-1,3-diene and cyclopentadiene, but the activation energies are almost in opposite correlation. This behavior is explained by the oxadiazole nitrogen lone pair repulsion with the π-orbitals of the nitrile groups.
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  • 20
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    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994), S. 213-215 
    ISSN: 0899-0042
    Keywords: ICRF-187 ; ICRF-186 ; ICRF-159 ; dexrazoxane ; doxorubicin ; dihydropyrimidine amidohydrolase ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enzymatic ring-opening hydrolyses of the doxorubicin cardioprotective agents (+)-(S)-ICRF-187 (dexrazoxane), (-)-(R)-ICRF-186, and rac-ICRF-159 by the enzyme dihydropyrimidine amidohydrolase (DHPase) have been studied. ICRF-187 underwent enzymatic ring-opening hydrolysis by DHPase 4.5 times faster than did ICRF-186. It was also shown that DHPase opens only one ring of ICRF-186 and does not act on this one-ring open hydrolysis product, as has been observed for ICRF-187. Differences in the rates at which the two optical isomers are acted upon by DHPase suggest that they could have differing protective effects. © 1994 Wiley-Liss, Inc.
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  • 21
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    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994), S. 216-219 
    ISSN: 0899-0042
    Keywords: supercritical fluid chromatography ; chiral separation ; NSAIDs ; ibuprofen ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Packed column SFC is used to resolve the enantiomers of two nonsteroidal antiinflammatories. A Chiralpak AD column is used with a binary mobile phase of carbon dioxide/methanol to achieve resolution. The effects of composition, pressure, temperature, and flow on ibuprofen enantiomer separation are examined. In this instance, temperature affords the greatest change in resolution followed by pressure and composition. Baseline resolution of ibuprofen is achieved in less than 7 min and fluibiprofen is baseline resolved in less than 4 min. © 1994 Wiley-Liss, Inc.
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  • 22
    ISSN: 0899-0042
    Keywords: thalidomide enantiomers ; HPLC ; hydroxylated metabolites ; mass spectrometry ; EM 12 ; in vitro metabolism ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The stereoselective metabolism of the former sedative thalidomide and the metabolism of its analogue EM 12 were studied in vitro with liver homogenates. In our study we focused on hydroxylated nonhydrolyzed metabolites of thalidomide. An analytical HPLC method was developed to determine these metabolites directly. The investigations showed a highly stereoselective biotransformation of thalidomide. 5-Hydroxy thalidomide was preferentially formed by (-)-(S)-thalidomide, whereas (+)-(R)-thalidomide was metabolized to two hitherto unknown compounds (Met A and B). Mass spectrometry of these metabolites Met A and B indicated that oxidation or hydroxylation took place in the glutarimide moiety. Biotransformation studies with the more stable thalidomide analogue EM 12 revealed four new metabolites (Met C—F) whose quantities differed in the selected liver homogenate. © 1994 Wiley-Liss, Inc.
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  • 23
    ISSN: 0899-0042
    Keywords: warfarin ; phenprocoumon ; CE ; chiral ; maltooligosaccharides ; enantiomeric excess ; assay ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The separation and quantitation of coumarinic anticoagulant drug enantiomers were achieved by direct chiral capillary electrophoresis using complex maltooligosaccharide mixtures as stereoselective electrolyte modifiers. Chiral separations were characterized by a high selectivity and efficiency, enabling enantiomeric excess determinations. In addition, preliminary results indicate the applicability of the method for the determination of individual enantiomers in biological samples. So the method can be used to perform stereoselective pharmacokinetic studies. © 1994 Wiley-Liss, Inc.
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  • 24
    ISSN: 0899-0042
    Keywords: HPLC ; reverse-phase additive ; β-cyclodextrin ; methylphenobarbitone ; molecular mechanics ; complex stability ; chiral separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Molecular modelling of β-cyclodextrin and optimisation of its potential energy suggests that a favoured conformation is that distorted from a symmetrical torus. The inclusion of water molecules into the torus cavity simulates the increased stability in an aqueous solvent. Complexes of β-cyclodextrin with (R)- and (S)-enantiomers of methylphenobarbitone have been modelled and energetically optimised by the application of molecular mechanics. The simulations suggests that the guest molecules adopt an orientation in which the phenyl ring is projected into the torus cavity, with in each case the plane of the ring parallel to a longer axis of the distorted torus and slightly displaced from the axis through the torus cavity. It is suggested that the asymmetry in the macrocyclic ring contributes to chiral recognition as a result of additional discriminatory binding to the barbiturate ring residue of each enantiomer, which occupy different 3D geometries. The enantiomers form complexes of different minimum potential energies. The resulting difference in complex stability can be related to the behaviour of β-cyclodextrin, as a mobile phase additive in reverse-phase HPLC to effect chiral separation of rac-medthylphenobarbitone during chromatography. © 1994 Wiley-Liss, Inc.
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  • 25
    ISSN: 0899-0042
    Keywords: hydroxychloroquine ; enantiomers ; stereoselectivity ; distribution ; interconversion ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Hydroxychloroquine (HCQ) stereoselective distribution was investigated in rabbits after 20 mg/kg po of racemic-HCQ (rac-HCQ) and 20 mg/kg po of each enantiomer, 97% pure (-)-(R)-HCQ and 99% pure (+)-(S)-HCQ. Concentrations were 4 to 6 times higher in whole blood than in plasma. Melanin did not affect plasma and whole blood levels since concentrations did not differ between pigmented and nonpigmented animals. After single and multiple doses of the separate enantiomers, only 5-10% of the antipode could be measured, in blood or plasma. Therefore, there was no significant interconversion from one enantiomer into the other. Following rac-HCQ, plasma (+)-(S)-levels always surpassed (-)-(R)-ones while in whole blood, (-)-(R)-HCQ concentrations were always the highest. When the enantiomers were administered separately, blood concentrations achieved after (-)-(R)-HCQ were higher, especially after multiple doses. These observations suggest that (-)-(R)-HCQ is preferentially concentrated by cellular components of blood. This enantioselective distribution of HCQ could be secondary to a stereoselective protein binding to plasma proteins, although a more specific binding of (-)-(R)-HCQ to blood cells cannot be ruled out. Since in whole blood (-)-(R)-HCQ is retained in cellular components, metabolism would favour the more available (+)-(S)-enantiomer. © 1994 Wiley-Liss, Inc.
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  • 26
    ISSN: 0899-0042
    Keywords: β-adrenergic blocking agent ; calcium antagonist ; enantiomers ; inflammation ; protein binding ; pharmacokinetics ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The influence of endotoxin-induced inflammation on the enantioselective pharmacokinetics of propranolol, oxprenolol, and verapamil, which bind to α1-acid glycoprotein, was studied in the rat. The racemic mixtures were given orally. In the control animals, for propranolol and oxprenolol, the plasma concentrations of the (R)-enantiomer were higher than those of the (S)-enantiomer, while for verapamil the reverse was true. Protein binding and intrinsic clearance are the main factors responsible for this enantioselectivity. After endotoxin treatment, for the three drugs tested the plasma concentrations and the plasma binding of both enantiomers were significantly increased. This effect was more pronounced for (R)-propranolol, (R)-oxprenolol, and (S)-verapamil than for their respective antipodes. The enantioselective effect of endotoxin on the plasma concentrations of the drugs studied seems mainly due to the enantioselective increase in binding to α1-acid glycoprotein. © 1994 Wiley-Liss, Inc.
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  • 27
    ISSN: 0899-0042
    Keywords: atenolol ; nitrile formation ; stability ; chromatography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The chemical stability of the acetamido moiety of the β-blocker atenolol toward possible dehydration causing a nitrile formation during an acid-catalyzed chiral derivatization procedure with O,O′-(R,R)-diacylated tartaric acid anhydrides was elucidated. All the necessary reference compounds including the oxazolidine-2-one derivatives of the respective aminopropanols were synthesized, their structures confirmed by various spectroscopic methods, and chromatographically compared using HPLC and GC-MS. In the course of this work it was shown that the acetamido moiety of atenolol is quite stable toward dehydrating agents but shows a significant thermolability, e.g., in the injection system of a GC, which leads to the dehydrated form of atenolol namely, “nitriloatenolol.” © 1994 Wiley-Liss, Inc.
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  • 28
    ISSN: 0899-0042
    Keywords: synthesis of enantiopure 2-, 3-, and 4-alkyl-branched acids ; diastereomeric phenylglycinol amides ; chain elongation by Arndt-Eistert synthesis ; malonic ester synthesis or via 2-alkylated alkyl carbonitriles ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A general approach to the synthesis of 2-, 3-, and 4-alkyl-branched acids of high enantiomeric purity is described. The enantiopure 2-alkyl-branched acids are prepared via liquid chromatographic resolution of diastereomeric phenylglycinol amides and their absolute configuration is deduced from the 1H-NMR data of the separated diastereomers. Chain elongation methods, by Arndt-Eistert synthesis, via 2-alkylated alkyl carbonitrile or by malonic ester synthesis, are used to prepare 3- and 4-alkyl-branched acids of high configurational purity and known absolute configuration starting from the enantiomeric 2-alkyl-branched acids. © 1994 Wiley-Liss, Inc.
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  • 29
    ISSN: 0899-0042
    Keywords: 2-, 3-, and 4-alkyl-branched acids ; enantioselective analysis ; sensory evaluation ; heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin ; octakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-γ-cyclodextrin ; Chamaemelum nobile (L.) Allioni ; Parmesan cheese ; red meat flavour ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Enantioselective GC analysis of 4-ethyloctanoic and 4-methylheptanoic acid, using heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin as the chiral stationary phase, is described and the sensory properties of several 4-alkyl-branched acids, using gas chromatography-olfactometry (GC-O) equipment and octakis(2,3-di-O-methyl-6-tert-butyldimethylsilyl)-γ-cyclodextrin as the stationary phase, are evaluated. The chirospecific analysis of various 2-, 3-, and 4-alkyl-branched acids from commercially available Roman chamomile (Chamaemelum nobile (L.) Allioni), Parmesan cheese, and subcutaneous mutton adipose tissue, using either GC-GC (MDGC) or GC-MS analytical methods, is described. © 1994 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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  • 30
    ISSN: 0899-0042
    Keywords: nonproteinogenic α-amino acid ; pronase ; optical resolution ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We describe a practical method to produce pure enantiomers of non-proteinogenic α-amino acids by pronase-catalyzed hydrolysis of their methyl esters. Each of the two pure enantiomers was obtained in high yield, while the reaction conditions were optimized with a view to large scale production. Part of this work was devoted to conceiving an analytical procedure especially designed to monitor the steric course of enzymatic reactions. © 1994 Wiley-Liss, Inc.
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  • 31
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994), S. 479-483 
    ISSN: 0899-0042
    Keywords: terfenadine metabolite ; enantiomer separation ; HPLC ; pharmacokinetics ; humans ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A stereoselective and sensitive achiral/chiral method for the determination of terfenadine acid metabolite in human plasma was developed. The metabolite was separated and quantitated using an achiral chromatographic procedure with a cyano column. The mobile phase was 1 mM sodium acetate buffer (pH 4.0) and acetonitrile (25:75% v/v) at a flow rate of 2 ml/min, at ambient temperature. The stereospecific resolution was accomplished using a chiral-AGP column and a mobile phase consisting of sodium acetate (0.01 M): methanol (98.7:1.3% v/v), and 20 mM di-n-butylamine at a flow rate of 1.2 ml/min. The column temperature was maintained at 32°C. The eluent was monitored at 230 nm (excitation) and 300 nm (emission) with a cut-off filter at 270 nm. This assay was used for a pharmacokinetic study in five subjects after administration of a single dose of 60 mg of terfenadine. The t½ values of the two enantiomers were similar, but the AUC values of the (+)-enantiomer were 2.05-2.35 times higher than those of (-)-enantiomer. © 1994 Wiley-Liss, Inc.
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  • 32
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994), S. 521-530 
    ISSN: 0899-0042
    Keywords: metallothionein ; copper binding ; glutathione ; circular dichroism ; charge transfer ; metal-ligand stoichiometries ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Metallothionein (MT) is a ubiquitous mammalian protein comprising 61 or 62 nonaromatic amino acids of which 20 are cysteine residues. The high sulfhydryl content imparts to this protein a unique and remarkable ability to bind multiple metal ions in structurally significant metal-thiolate clusters. MT can bind seven divalent metal ions per protein molecule in two domains with exclusive tetrahedral metal coordination. The domain stoichiometries for the M7S20 structure are M4(Scys)11 (α domain) and M3(Scys)9 (β domain). Up to 12 Cu(I) ions can displace the 7 Zn2+ ions bound per molecule in Zn7-MT. The incoming Cu(I) ions adopt a trigonal planar geometry with domain stoichiometries for the Cu12S20 structure of Cu6(Scys)11 and Cu6(Scys)9 for the α and β domains, respectively. The circular dichroism (CD) spectra recorded as Cu+ is added to Zn7-MT to form Cu12-MT directly report structural changes that take place in the metal binding region. The spectrum arises under charge transfer transitions between the cysteine S and the Cu(I); because the Cu(I)-thiolate cluster units are located within the chiral binding site, intensities in the CD spectrum are directly related to changes in the binding site. The CD technique clearly indicates stoichiometries of several Cu(I)-MT species. Model Cu(I)-thiolate complexes, using the tripeptide glutathione as the sulfhydryl source, were examined by CD spectroscopy to obtain transition energies and the Cu(I)-thiolate coordination geometries which correspond to these bands. Possible structures for the Cu(I)-thiolate clusters in the α and β domains of Cu12-MT are proposed. © 1994 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
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  • 33
    ISSN: 0899-0042
    Keywords: arylpropionic acid ; ketoprofen ; chiral inversion ; stereoselective pharmacokinetics ; monkey ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Pharmacokinetic studies are reported after single oral administration of 3 mg/kg of stereochemically pure (S)-ketoprofen [(S)-KP] and (R)-ketoprofen [(R)-KP] to three male Cynomolgus monkeys and after repeated administration for 6 months of 3, 15 and 75 mg/kg/day of (S)-KP to both male and female monkeys. A high-performance liquid chromatographic (HPLC) analysis was performed without derivatization of the samples, using a chiral column. The pharmacokinetic parameters for (S)-KP after administration of (S)-KP and for (R)-KP after administration of (R)-KP were, respectively, elimination half-life 2.32 ± 0.36 and 1.64 ± 0.40 h; oral clearance 3.50 ± 0.66 and 7.50 ± 3.20 ml/min/kg; apparent volume of distribution 0.74 ± 0.24 and 1.16 ± 0.76 liter/kg; mean residence time 1.79 ± 0.77 and 1.41 ± 0.65 h; area under the concentration/time curve 14.16 ± 2.93 and 7.31 ± 2.98 μg·h/ml. Forty-nine percent unidirectional bioinversion of (R)-KP to (S)-KP was observed in this species and the pharmacokinetic parameters for the (S)-KP resulting from this inversion were also calculated. In the study of 6-month repeated administration of (S)-KP, linear pharmacokinetic behavior and no evidence of drug accumulation were observed at the three dose levels. © 1994 Wiley-Liss, Inc.
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  • 34
    ISSN: 0899-0042
    Keywords: high-performance liquid chromatography ; chiral stationary phase ; optical isomer resolution ; ergot alkaloids ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A new covalently-bonded, silica-based stationary phase, using as the chiral selector the 1-(3-aminopropyl) derivative of (+)-(5R,8S,10R)-terguride, has been developed to resolve optically active isomers by HPLC. Good resolution of structurally related racemic ergot alkaloids were obtained using water-methanol mixtures as the eluent. Analysis of the influence of the type and concentration of the organic modifier, and the pH of the buffer in the mobile phase allowed the enantioseparation of these compounds to be optimized. Determination of the optical purity of a lisuride-containig drug is reported. © 1994 Wiley-Liss, Inc.
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  • 35
    ISSN: 0899-0042
    Keywords: diastereoisomer complexes ; nuclear magnetic resonance spectroscopy ; ergot alkaloid derivatives ; haproxen enantiomers ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 1H NMR (600 MHz) measurements of chemical shift changes were made in acidified (DCI) CD3OD/D2O 1:9 v/v equimolar solutions of (S)- and (R,S)-6-methoxy-α-methyl-2-naphthaleneacetic acid (naproxen) in the presence of 1-(3-aminopropyl)-(5R,8S,10R)-terguride (AMP-TER). The most significant bonding interactions concurring to the formation of diastereoisomer complexes are seen as chemical shifts in proximity to the positively charged nitrogen N(6)-CH3 and of H(12), H(13), H(14) protons of the ergoline skeleton, both the adducts having an electrostatic term and different π-π stabilizing interactions. Chemical shift data exclude any contribution of the aminopropyl chain to the chiral recognition mechanism. These findings provide an experimental basis for the enantiodiscriminative process accounting for the observed chromatographic resolutions of arylcarboxylic acids on chiral stationary phases derived from AMP-TER. © 1994 Wiley-Liss, Inc.
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  • 36
    ISSN: 0899-0042
    Keywords: mianserin ; enantiomer ; metabolism ; human plasma ; urine ; HPLC ; CYP2D6 ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An HPLC method is presented which allows the measurement in the same run of the enantiomers of mianserin, desmethylmianserin, and 8-hydroxymianserin in plasma and urine of mianserin-treated patients. Limits of quantitation for the (S)- and (R)- enantiomers of mianserin and desmethylmianserin were 4 and 2.5 ng/ml, respectively, in plasma, and for the (S)- and (R)-enantiomers of mianserin, desmethylmianserin, and 8-hydroxymianserin 5, 2.5, and 5 ng/ml, respectively, in urine. The measured ratios of (S)-mianserin/(R)-mianserin and (S)-desmethylmianserin/(R)-desmethylmianserin in the plasmas of 10 mianserin-treated patients, all extensive metabolizers of debrisoquine as determined by CYP2D6 genotyping, varied, respectively, from 1.0 to 4.06 and from 0.19 to 0.64. As the enantiomers of mianserin differ in their pharmacological profile, these results could partially explain why, until now, no consistent relationship has been established between the therapeutic response and total [(S) + (R)] plasma levels of this antidepressant. © 1994 Wiley-Liss, Inc.
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  • 37
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994), S. 564-571 
    ISSN: 0899-0042
    Keywords: achiral/chiral chromatography ; chiral HPLC ; circular dichroism ; Dictyostelium discoideum ; flavoprotein column ; fluorescence ; pteridines ; stereoconfiguration ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Optically active lumazines (biolumazine, dictyolumazine, monalumazine, and neolumazine) are prepared from the corresponding pterins by enzymatic reaction, using pterin deaminase excreted by Dictyostelium discoideum. The fluorescence properties, circular dichroism spectra, and chromatographic behavior of these lumazines are studied. D- and L-enantiomers of biolumazine, dictyolumazine, and monalumazine are separated using a chiral flavoprotein column. This column also separates the enantiomeric pterins of the threo form: monapterin and dictyopterin. However, the column does not separate the enantiomeric pterins of the erythro form: neopterin and biopterin. By coupling a reverse-phase column to the flavoprotein column, the separation of pterins and lumazines in function of their hydrophobicity, as well as the separation of the diastereomers, is achieved. This coupled achiral/chiral high-performance liquid chromatography method enables determination of the stereoconfiguration of natural lumazines by comparison with optically pure compounds. A lumazine derivative, present in the extracellular medium of Dictyostelium discoideum, is identified as D-dictyolumazine, i.e., 6-(D-threo-1,2-dihydroxypropyl)-lumazine. © 1994 Wiley-Liss, Inc.
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  • 38
    ISSN: 0899-0042
    Keywords: microsomal epoxide hydrolase ; kinetic parameters ; enantiomeric excesses ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The microsomal epoxide hydrolase (mEH)-catalyzed hydrolysis of cis-4,4′-dimethylstilbene oxide (1a), cis-4,4′-diethylstilbene oxide (1b), cis-4,4′-diisopropylstilbene oxide (1c), and cis-4,4′-dichlorostilbene oxide (1d) have been investigated using rabbit liver microsomal preparations. The kinetic parameters, Km and Vmax, and the absolute stereochemistry of the reactions have been determined and compared with those of cis-stilbene oxide (1e). All epoxides 1a-d are hydrolyzed by mEH with high product enantioselectivity to give (R,R)-(+)-diols with ee ≥ 90%. The presence of the substituents on the phenyl rings markedly reduces the rates of mEH catalyzed hydrolysis with respect to cis-stilbene oxide, by increasing Km and reducing Vmax in the cases of 1a, 1b, and 1d, or reducing only the Vmax in the case of 1c. The very low Vmax, together with a persistent ability to fit into the mEH active site, make all these epoxides, and particularly 1c, inhibitors of cis-stilbene oxide hydrolysis. The kinetic and stereochemical results are interpreted on the basis of the proposed topology of the mEH active site. © 1994 Wiley-Liss, Inc.
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  • 39
    ISSN: 0899-0042
    Keywords: resolution ; D,L-amino acid esters ; alkaline protease ; simple separation ; high enantiomeric excess and yields ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We developed a procedure for the resolution of esters of amino acids in 95% t-butanol, followed by saponification of the unreacted esters to afford both enantiomers with high yield and optical purity. The hydrolysis, catalyzed by alkaline protease, was conducted in a mixture of t-butanol (95%) and water (5%) at 25°C, with a pH controlled at pH 8.5 by the addition of NaOH (2 M). The hydrolyzed L-amino acid, which was insoluble under these conditions, precipitated during the course of hydrolysis. After separation of the precipitate, the pH of the filtrate was adjusted to 11.5 to saponify the unreacted ester. The D-antipode precipitated at pH 6.2-6.5. Both optically pure antipodes were obtained with high enantiomeric excesses and yields by simple filtration. © 1994 Wiley-Liss, Inc.
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  • 40
    ISSN: 0899-0042
    Keywords: chiral HPLC ; resolution ; absolute configuration ; X-ray analysis ; GABAB antagonist ; GABAB receptor affinity ; phaclofen ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Phaclofen, which is the phosphonic acid analogue of the GABAB agonist (RS)-3-(4-chlorophenyl)-4-aminobutyric acid (baclofen), is a GABAB antagonist. As part of our studies on the structural requirements for activation and blockade of GABAB receptors, we have resolved phaclofen using chiral chromatographic techniques. The absolute stereochemistry of (-)-(R)-phaclofen was established by X-ray crystallographic analysis. (-)-(R)-Phaclofen was shown to inhibit the binding of [3H]-(R)-baclofen to GABAB receptor sites on rat cerebellar membranes (IC50 = 76 ± 13 μM), whereas (+)-(S)-phaclofen was inactive in this binding assay (IC50 > 1000 μM). (-)-(R)-Phaclofen (200 μM) was equipotent with (RS)-phaclofen (400 μM) in antagonizing the action of baclofen in rat cerebral cortical slices, while (+)-(S)-phaclofen (200 μM) was inactive. The structural similarity of the agonist (R)-baclofen and the antagonist (-)-(R)-phaclofen suggests that these ligands interact with the GABAB receptor sites in a similar manner. Thus, it may be concluded that the different pharmacological effects of these compounds essentially result from the different spatial and proteolytic properties of their acid groups. © 1994 Wiley-Liss, Inc.
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  • 41
    ISSN: 0899-0042
    Keywords: antiarrhythmic drug ; mexiletine ; absolute configuration ; X-ray analysis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Data on the absolute configuration of mexiletine (MEX) do not appear to have been published, although in several published reports the configuration is referred to as (-)-(R) and (+)-(S), based on information from manufactures providing the drug stereoisomers. We demonstrate that (-)-MEX has the (R)-configuration by mean of a new stereospecific synthesis. X-Ray analysis of an optical active sample of (+)-MEX as its hydrobromide salt, obtained from chemical resolution of the racemic mixture, was carried out in order to obtain precise information on bond lengths and angles, useful for studies on structure-activity relationships. We also report the NMR analysis in presence of Eu(hfc)3 as shift reagent, which represents a simple method for the determination of enantiomeric excess (ee) in addition to the well-known chiral HPLC methods. © 1994 Wiley-Liss, Inc.
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  • 42
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    Chirality 6 (1994), S. 605-605 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 43
    ISSN: 0899-0042
    Keywords: semipreparative separation ; enantiomers ; chromatography ; tri-acetylcellulose ; melatonin ; 2-amidotetralins ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In order to obtain milligram amounts of the enantiomers of a series of compounds to be tested for binding to the melatonin binding site, a system for semipreparative enantiomeric separation was set up using tri-acetylcellulose as the chiral stationary phase. Interactions of this class of compounds with tri-acetylcellulose were examined on an analytical scale with a series of 20 compounds. Apparently, both steric and electrostatic interactions determine retention behavior on tri-acetylcellulose. Semipreparative separations were carried out for a subset of seven compounds. The purity of the first eluting enantiomer usually was around 99%, whereas the purity of the second eluting enantiomer was slightly less. The system described is easy to use and has the major advantage that a series of compounds can be separated with one technique. The purities obtained are sufficient for a first screen of their affinity. © 1994 Wiley-Liss, Inc.
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  • 44
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 45
    ISSN: 0899-0042
    Keywords: cimetidine ; sulfoxidation ; urinary metabolite ; enantiomeric composition of cimetidine sulfoxide ; sequential achiral - chiral high-performance liquid chromatography ; preparative chromatographic resolution ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The individual enantiomers of cimetidine sulfoxide were resolved by preparative chromatography using a Chiralcel OC stationary phase and were characterized by the determination of optical rotation and circular dichroism spectra. Cimetidine sulfoxide was isolated from the urine of two healthy male volunteers following oral administration of cimetidine (400 mg). Urine was collected every 2 h for 12 h postdosing, after which time HPLC analysis indicated negligible recovery of the drug as the sulfoxide. Some 7% of the dose was recovered as cimetidine sulfoxide over this period. The enantiomeric composition of cimetidine sulfoxide was determined by sequential achiral - chiral chromatography using the OC phase. Over the collection period the enantiomeric ratio was found to be constant in all samples at (+/-) of 71 ± 2.5:29 ± 2.5. The enantiomeric composition of cimetidine sulfoxide was also determined in rat urine (24 h) following the administration of cimetidine (30 mg/kg po) to male Wistar rats (n = 7). The enantiomeric ratio in this case was found to be (+/-) 57 ± 2.3:43 ± 2.3. These preliminary data indicate that sulfoxidation of cimetidine is stereoselective with respect to the (+)-enantiomer and that species variation in enantiomeric composition occurs. © 1994 Wiley-Liss, Inc.
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  • 46
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994), S. 615-622 
    ISSN: 0899-0042
    Keywords: absolute configuration ; chiral stationary phase ; enantiomer ; chiral recognition ; NSAID ; HPLC ; NMR ; CD ; X-ray ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Assignment of absolute configuration to a recently developed chiral selector useful in the separation of the underivatized enantiomers of naproxen and other nonsteroidal anti-inflammatory drugs (NSAIDs) is described. Circular dichroism, 1H NMR, and X-ray diffraction have been used to confirm the original assignment which was based solely upon elution orders from HPLC chiral stationary phases. All of these techniques agree in the assignment of the (S,S) absolute configuration to the enantiomer of the chiral selector which associates preferentially with (S)-naproxen. © 1994 Wiley-Liss, Inc.
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  • 47
    ISSN: 0899-0042
    Keywords: chiral stationary phases ; resolution of enantiomers ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The determination of enantiomeric purity of (R)- and (S)-2-hydroxy-4-phenylbutyric acid by chiral HPLC is described. Good resolution has been obtained on covalently bonded L-hydroxyproline saturated with Cu(II) ions. The method makes possible the determination of enantiomeric purity in media containing growing cells. © 1994 Wiley-Liss, Inc.
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  • 48
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994), S. 623-626 
    ISSN: 0899-0042
    Keywords: rat ovary microsomal aromatase ; enantiomers ; aminoglutethimide ; rogletimide ; cyclohexylaminoglutethimide ; stereochemical configurations ; aromatase inhibitors ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The in vitro aromatase activity in microsomal fractions from rat ovary and its inhibition by enantiomers of aminoglutethimide (AG), rogletimide (RG), and cyclohexylaminoglutethimide (ChAG) were studied by analysing the [3H]H2O released when [1β-3H]androstenedione was converted to estrone. Maximum velocity (Vmax) and the Michaelis-Menten constant (Km) of the microsomal aromatase enzyme were 17.40 ± 0.45 pmol/ml/mg protein/min and 1.02 ± 0.06 μM, respectively. The IC50s for the enantiomers were similar for (+)-R-AG and (-)-R-ChAG (0.86 ± 0.06 and 0.89 ± 0.15 μM, respectively). (+)S-ChA'G was most potent with IC50 of 0.075 ± 0.003 μM. The IC50s for (-)-S-AG, (+)-R-RG, and (-)-S-RG were in the same range (23.15 ± 2.74, 24.58 ± 2.46, and 24.43 ± 2.20 μM, respectively). © 1994 Wiley-Liss, Inc.
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  • 49
    ISSN: 0899-0042
    Keywords: benztropine ; histamine ; H1-receptors ; molecular modelling ; 4-methyl-diphenhydramine ; stereoselectivity ; synthesis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A series of optically active analogues of the H1-antihistamine ebastine, with chiral center(s) at the benzhydryl and/or phenylbutyl part of the molecule, have been synthesized. Their in vitro antihistaminic and antimuscarinic activities were investigated, along with a molecular modelling study. It was found that introduction of the benzhydryl chiral center yielded significant stereoselectivity for both antihistaminic and antimuscarinic activities. The steric preferences of the benzhydryl chiral center for antihistaminic and antimuscarinic actions were mirror images of each other. The (-)-isomer of 4-methylebastine (6d) showed more than 10-fold higher in vitro antihistaminic potency than ebastine. Meanwhile the selectivity of 6d for histamine H1-receptors was also increased by more than 20 times in comparison with ebastine. The chirality at the phenylbutyl part of the molecule does not significantly alter the antihistaminic or antimuscarinic activity of the compounds although the (S)-isomers showed slightly but unanimously higher antihistaminic activity than the (R)-isomers. These results have been discussed with existing stereoselectivity data of antihistamines and an asymmetric pharmacophore model for H1-antagonists has been described. © 1994 Wiley-Liss, Inc.
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  • 50
    ISSN: 0899-0042
    Keywords: organogels ; reversed micelles ; Aerosol-OT ; lipase ; 2-methylbutyric acid ; ethyl-2-methylbutyrate ; enantioselective reaction resolution ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Chromobacterium viscosum lipase (c.v. lipase) was immobilized in microemulsion-based órganogels and successfully utilized for the enantioselective esterification of (+/-)-2-methylbutynic acid to preferentially form ethyl-(+)-2-methylbutyrate. The reaction time course and enantioselectivity obtained with the organogel - lipase system was compared and contrasted to that achieved in a reversed micellar solution system that contained lipase solubilized in its inner water core as well as that in which powdered lipases were directly dispersed in an organic solvent. The unique properties and potential benefits of the organogel system are discussed. © 1994 Wiley-Liss, Inc.
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  • 51
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994), S. 654-657 
    ISSN: 0899-0042
    Keywords: successive optical resolution ; replacing crystallization ; threonine ; optically active cosolute ; L-serine ; 4-hydroxy-L-proline ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: DL-Threonine [DL-Thr; (2RS,3SR)-2-amino-3-hydroxybutanoic acid] was optically resolved by replacing crystallization using L-serine (L-Ser) and 4-hydroxy-L-proline (L-Hyp) as optically active cosolutes. D-Thr was allowed to crystallize preferentially from racemic aqueous solutions in the presence of these L-α-amino acids. The optical resolution of DL-Thr was more successfully achieved by using L-Ser, whose structure is more similar to that of DL-Thr than L-Hyp, and successively gave D- and L-Thr of 87 - 92% optical purities. The D- and L-Thr obtained were then recrystallized from water to give optically pure D- and L-Thr. © 1994 Wiley-Liss, Inc.
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  • 52
    ISSN: 0899-0042
    Keywords: ketorolac ; nonsteroidal antiinflammatory drugs ; chiral drugs ; enantiomers ; protein binding ; human serum albumin ; enantioselectivity ; pharmacokinetics ; fatty acids ; oleic acid ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The protein binding of the enantiomers of the nonopiate analgesic, ketorolac, was investigated in vitro using human plasma and solutions of human serum albumin (HSA) at physiological pH and temperature. In order to detect the very low levels of unbound enantiomers in protein solutions, tritium-labelled rac-ketorolac was synthesised by regiospecific isotopic exchange of the parent drug with tritiated water as the isotope donor. Radio-chemical purification of this compound by reversed-phase HPLC followed by direct resolution using a chiral α1-acid glycoprotein (Chiral-AGP) HPLC column afforded labelled enantiomers of high specific activity. The in vitro use of (R)- and (S)-[3H4]ketorolac enabled reproducible radiometric detection of enantiomers in protein solution ultrafiltrate. The unbound fractions of (R)- and (S)-ketorolac [fu(R) and fu(S), respectively] were determined when drug was added to various plasma or albumin solutions as either the separate enantiomers or as the racemate. Over an enantiomeric plasma concentration range of 2.0 - 15.0 μg/ml, fu(S) (mean range: 1.572 - 1.795%) was more than 2-fold greater (P < 0.001) than fu(R) (mean range: 0.565 - 0.674%). Both fu(R) and fu(S) were constant over this concentration range, and each was unaffected by the presence of the corresponding antipode (P > 0.05). At a concentration of 2.0 μg/ml in 40.0 g/liter fatty acid-free HSA, fu(R) and fu(S) were approximately 0.5 and 1.1%, respectively, and both values declined with increasing concentrations of the long chain fatty acid, oleic acid. We have previously shown that the pharmacokinetics of ketorolac in humans are markedly enantioselective and suggest in this report that these differences are largely the result of substantial differences in the protein binding of ketorolac enantiomers. These findings stress the importance of monitoring the unbound concentrations of the enantiomers of chiral drugs if correct interpretations are to be made of enantioselective pharmacokinetic data. © 1994 Wiley-Liss, Inc.
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  • 53
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994), S. 658-664 
    ISSN: 0899-0042
    Keywords: host-guest cyclodextrin complexes ; asymmetric induction ; solid-state reaction ; substituent effect ; steric restrictions ; hydrophobic interactions ; hydrogen bonding ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The effect of substituent groups on asymmetric induction by β-cyclodextrin (β-CD) was investigated in the reduction of a series of o-, m-, and p-substituted acetophenones (X = H, Br, Cl, CH3, NO2, OCH3) with aqueous NaBH4. The inclusion of the ketones studied in β-CD led to water-insoluble compounds so that the reaction proceeded in the solid state. The substitutions resulted generally in higher enantioselectivities than that obtained for acetophenone indicating stronger host - guest interactions. Acetophenone and its m- and p-derivatives gave preponderantly the (-)-alcohol while the prevailing enantiomer was the (+)-alcohol in the case of the o-derivatives. The enantioface selectivity was found to be mainly governed by steric demands imposed by the size and the shape of the β-CD cavity in the case of the o-substituted acetophenones and by hydrophobic interactions in the case of the m-derivatives. A more complicated situation arose from the asymmetic reduction of p-derivatives where a combination of these factors with hydrogen bonding of the carbonyl group to the hydroxyls of β-CD are responsible for the enantioselectivity. © 1994 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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  • 54
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994), S. 665-669 
    ISSN: 0899-0042
    Keywords: circular dichroism ; amphotericin B ; self-association ; manomer/oligomer ; solvent effects ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Circular dichroism (CD) spectroscopy has been used to evaluate the ability of 21 different solvents to influence the aggregation state of amphotericin B. Using the relative donor/acceptor tendencies known for each solvent system, it was possible to deduce information as to the factors which goven the self-association of amphotericin B. It was concluded that in the absence of strong solvent interaction, amphotericin B prefers to self-associate into oligomeric species. This intrinsic driving force can be overcome through the use of solvents which function as strong electron pair donors, probably forming specific solvent - solute species. © 1994 Wiley-Liss, Inc.
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  • 55
    ISSN: 0899-0042
    Keywords: sharpless asymmetric epoxidation ; detailed synthesis ; enantiomeric separations; diastereomeric separations ; cis- and trans-epoxy alcohols ; cis- and trans-allylic alcohols ; homoallylic alcohol ; chiral HPLC ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The detailed synthesis of (2R,3R)-3-benzylglycidol by the Sharpless asymmetric epoxidation route is described. The enantiomeric purity determination of this compound is complicated by the presence of small quantities of the diastereometric (2R,3S)-3-benzylglycidol from the asymmetric epoxidation of the cis-allylic alcohol, and the unreacted allylic alcohols that are not removed in the product isolation steps. We have developed a direct chiral HPLC method that can resolve all these components for the precise determination of enantiomeric excesses of chiral 3-benzylglycidols. © 1994 Wiley-Liss, Inc.
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  • 56
    ISSN: 0941-1216
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Synthesis of Sulfonylsubstituted Heterocycles by Cyclocondensation of Sulfones with Bifunctionalised Compounds2-Sulfonylketendithioacetales (1), alkyl-sulfonylacetates (6), 2-sulfonyl-acetophenones (9) and -nitriles (12) react by cyclocondensation with bifunctionalised compounds 2, 4, 7, 10 and 13 yielding the sulfonylsubstituted chinoline- 3, chinolone- 5, barbituric acid- 8, pyrane- 11 and coumarine 15 derivatives.
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  • 57
    ISSN: 0941-1216
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Silver(I) Complexes of 3-Substituted 1-Methyl-perhydro-1,2,4-triazine-5,6-dithionesHeterocyclic triazine compounds such as 1-methyl-perhydro-1,2,4-triazin-5,6-dithiones react with silver salts forming complex species [AgL2]+ (L = triazinedithione). In water the complexes are unstable owing to ligand hydrolysis. Stable solid complex [AgL2]Br(L = 1,3,3-trimethyl-perhydro-1,2,4-triazine-5,6-dithione) can be obtained by the digestion of AgBr-microcrystals with the triazinedithione in methanol. As shown by X-ray crystal structure analysis the silver ion in this complex is coordinated trigonal pyramidal by four sulfur donor atoms.
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  • 58
    ISSN: 0941-1216
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Oxidation of Pyrazolinones