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  • 1995-1999
  • 1990-1994  (1,270)
  • 1993  (1,270)
  • Organic Chemistry  (969)
  • Atomic, Molecular and Optical Physics  (301)
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  • 1995-1999
  • 1990-1994  (1,270)
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  • 1
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0899-0042
    Keywords: enantiomers ; conjugates ; protein binding ; tissue binding ; stereoselective pharmacokinetics ; first-pass effect ; drug metabolism ; liver disease ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: As an experimental model for reduced liver function rats with surgical portacaval shunts (pcs) may be used. Carvedilol, a nonselective β-adrenoceptor antagonist with vasodilating activity, is extensively metabolised by phase I as well as phase II pathways. In order to study the stereoselective pharmacokinetics of carvedilol in liver disease, pcs and control rats were given rac-carvedilol intravenously and p.o. The carvedilol enantiomers and their conjugates were assayed in plasma, urine, and bile. Carvedilol was highly bound to plasma proteins; binding was reduced by pcs. In all groups, the plasma concentrations of (R)-carvedilol exceeded those of (S)-carvedilol significantly. In comparison to the control group the plasma concentrations of both enantiomers increased after pcs, while the difference between the stereoisomers decreased. The total clearance decreased proportionally to the decrease in liver weight (30%). Both the apparent oral clearance, as well as its stereoselectivity were reduced, by up to 90 and 43%, respectively. The biliary clearance of the parent drug after i.v. dosage increased in rats with pcs due to the reduced hepatic metabolism. © 1993 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
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  • 3
    ISSN: 0899-0042
    Keywords: stereoselective excretion ; enantioselective ; chromatography ; assay validation ; hydroxychloroquine metabolism ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A sequential achiral-chiral high-performance liquid chromatographic system has been developed for the quantitation in urine of the enantiomers of hydroxychloroquine (HCQ), and of its 3 major metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ). HCQ and its metabolites were separated and quantified on a cyano-bonded phase, and the enantiomeric ratios were determined using a Chiral-AGP chiral stationary phase. The assay validation and application of this method to a preliminary study in a human volunteer are presented. In this subject, the initial 0-4 h urine contained the 2 HCQ enantiomers in a ratio of (+)-HCQ:(-)-HCQ of 3:2; by the 2,064 h of the study, this ratio had reversed to (+)-HCQ:(-)-HCQ of 3:7. © 1993 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 8-14 
    ISSN: 0899-0042
    Keywords: (±)- ; (±)- ; (-)-atenolol ; sotalol ; amosulalol ; enantiomers ; β1 - and β2-adrenoceptors ; rat left atria and portal vein ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The effects of (±)-, (+)-, and (-)-atenolol, sotalol, and amosulalol alone on the rat left atria and portal vein and on the respective β1- and β2-adrenoceptor-mediated responses to isoprenaline have been determined. (±)-Atenolol at 10-6 M had no effect whereas high concentrations of (+)- and (-)-sotalol, 10-5-10-4 M, and (±)-, (+)-, and (-)-amosulalol depressed the response of the rat left atria to cardiac stimulation which indicates membrane stabilizing activity. None of the drugs tested had any effect alone on the rat portal vein. The order of potency as antagonists was (±)-amosulalol 〉 (±)-atenolol 〉 (±)-sotalol at β1-adrenoceptors and (±)-amosulalol 〉 (±)-sotalol 〉 (±)-atenolol at β2-adrenoceptors. (±)-Atenolol and (±)-amosulalol are β1-selective whereas (±)-sotalol is β2-selective. For each of the racemic β-blockers, the β1- and β2-adrenoceptor blocking activity was predominantly due to the (-)-enantiomer. © 1993 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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  • 5
    ISSN: 0899-0042
    Keywords: (+)-(2S,3S)-cis-2,3-dihydro-2-[(methylamino)methyl]-1-[4-(trifluoromethyl)phenoxy]-1H-indene hydrochloride ; serotonin uptake inhibitor ; circular dichroism ; benzene sector and chirality rules ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The absolute configuration of (+)-cis-2,3-dihydro-2[(methylamino)methyl]-1-[4-(trifluoromethyl)pheno〈y]-1H-indene hydrochloride, the more active enantiomer of a new serotonin inhibitor, was established as 1S,2S. This assignment was based on the application of the benzene sector and chirality rules to the interpretation of the inhibitor's circular dichroism spectrum and the spectra of other related chiral 1-substituted 2,3-dihydro-1H-indenes. © 1993 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
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  • 6
    ISSN: 0899-0042
    Keywords: enantiomeric separation ; chiral phase ; ovomucoid ; octahydrobenzo(g) quinoline ; chiral recognition mechanism ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantiomeric resolution of six closely related hexa- and octa-hydrobenzo(g) quinoline racemates by HPLC on an ovomucoid column (Ultron ES-OVM) is described. First, the influence of uncharged mobile phase additives (with different hydrogen bonding properties) and pH on retention and enantioselectivity is investigated. It is shown that an optimum pH of around 6 for the given separations is much more important than the choice of modifier. Second, the influence on enantioselectivity of small differences in molecular structure is examined. In one case a large difference is obtained for diastereomeric racemates depending on the cis- or trans-configuration of the quinoline skeleton. Higher flexibility of the solute seen in the cis enantiomers seems to improve enantioselectivity. © 1993 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 320-328 
    ISSN: 0899-0042
    Keywords: lipases ; amano M-AP-10 ; transesterification ; hydrolysis ; aminolysis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Enzyme-catalyzed reactions in organic media of rac-ketoprofen esters with different nucleophiles such as alcohols, amines, and water have been studied. Among the parameters optimized are the enzyme, the activated substrate, and the solvent. With the enzymes used in this study the preferred substrate was the trifluoroethyl ester of rac-ketoprofen (rac-2), whose (R)-enantiomer reacted preferentially. The enzyme of choice was the lipase M-AP-10 from Mucor miehei and best results were obtained with diisopropyl ether as solvent. Three different methods have been scaled-up for the resolution of 75-150 g of substrate: transesterification with 1-butanol (90% yield of (S)-ketoprofen, 88% ee), transesterification with 2-(2-pyridyl)ethanol (94% yield, 92% ee), and hydrolysis in wet organic solvent (93% yield, 97% ee). Despite the comparable chemical and optical yields obtained with these three methods, the use of 2-(2-pyridyl)ethanol and the hydrolysis allowed a much easier work-up and isolation of the desired (+)-(S)-ketoprofen. © 1993 Wiley-Liss, Inc.
    Additional Material: 7 Tab.
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 334-337 
    ISSN: 0899-0042
    Keywords: lactone synthesis ; stereoselective oxidation ; monooxygenases ; Pseudomonas putida NCIMB 10007 ; Acinetobacter calcoaceticus NCIMB 9871 ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The current practices of using monooxygenase enzymes to perform regio- and stereoselective oxidation reactions in organic syntheses are reviewed. The isolation of a monooxygenase from Pseudomonas putida NCIMB 10007 and its use in the conversion of bicyclo[3.2.0]hept-2-en-6-one into two isomeric optically active lactones is described. The monooxygenase utilises NADH as cofactor and NADH-recycling is accomplished using formate and formate dehydrogenase. As alternative methodology, it is shown that a secondary alcohol can be converted into a chiral lactone using a dehydrogenase and a monooxygenase working in tandem with in situ cofactor recycling. © 1993 Wiley-Liss, Inc.
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 350-355 
    ISSN: 0899-0042
    Keywords: adrenoceptors ; formoterol ; eudismic ratios ; diastereomers ; stereoselectivity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The knowledge that enantiomers of chiral compounds may differ widely in biological activity, qualitatively as well as quantitatively, is not new. Nevertheless most of the pharmacological data available to date on chiral drugs are obtained from experiments with racemates which assume that the biological activity generally resides in one of the enantiomers. With the advancements made in stereospecific synthesis and stereoselective analysis of drugs pharmacologists are now offered new possibilities to explore the steric aspects of drug action. This survey will discuss pharmacological data obtained with enantiomer pairs of phenylethylamine derivatives which interact with adrenergic mechanisms. The degree of resolution is seldom specified in published work on stereoselectivity of drugs. In a recent study from our laboratory the enantiomers of the β2-adrenoceptor agonist formoterol and their diastereomers have been evaluated. We found that the (R;R)-enantiomer was by far the most potent. However, the relative potencies obtained for the (R;S)-, (S;R), and (S;S)- isomers were critically dependent on the degree of enantiomeric purity. It is concluded that the certainty of potency ratios observed for chiral drugs is limited by the enantiomeric purity and by unspecific effects of the least active enantiomer at very high concentrations. © 1993 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
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  • 10
    ISSN: 0899-0042
    Keywords: amplification of enantiomeric excess ; autocatalysis ; origin of optical activity ; models ; nonlinear kinetics ; simulations ; stereoselectivity ; tetralin hydroperoxide ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The autoxidation of tetralin is treated as a model reaction system to define the applicability of stereospecific autocatalysis. This concept, predicting a spontaneous amplification of enantiomeric excess generated by an autocatalytic chemical reaction, is used in several theoretical models as an explanation for the origin of natural optical activity. The reaction system investigated obeys the basic criteria of these models: a chiral intermediate (tetralin hydroperoxide) is produced from an achiral substrate (tetralin) via an autocatalytic pathway where the feedback mechanism is expected to generate a state of broken chiral symmetry. In order to test the amplification capacity of this reaction a computer analysis of the kinetic scheme is performed. This simulation is derived from the known kinetic scheme of autoxidation and is validated by fitting the experimentally observed data of hydroperoxide evolution. Calculations show that this model allows powerful amplification of enantiomeric excess and a transient amplification of the optical rotation. It is also demonstrated that the model system exhibits pronounced sensitivity toward any loss of absolute configuration of the involved chiral species. Since an amplification effect results exclusively at a high degree of stereoselectivity, it is concluded that stereospecific autocatalysis is possible in systems which show template reactions, crystallization, or colloidal effects. © 1993 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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  • 11
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 370-374 
    ISSN: 0899-0042
    Keywords: (+)-chlorthalidone ; racemization ; pH profile ; influence of liposomes ; reaction kinetics ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The extent of racemization of (+)-chlorthalidone as a function of pH is examined. The minimum of the log K/pH curve is pH 3. The reaction mechanism of inversion is postulated to involve a carbenium cation over the entire pH range and a ring opening reaction in the alkaline range. The influence of liposomes on the inversion rate is also studied, retardation of the racemization rate being observed with increasing liposome concentration. A model of drug distribution between liposome phase and aqueous phase based on the Nernst distribution principle is presented and reaction kinetic aspects are considered. © 1993 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
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  • 12
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 400-402 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 2 Ill.
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  • 13
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 403-403 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 14
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 191-198 
    ISSN: 0899-0042
    Keywords: stereoselectivity ; regioselectivity ; aliphatic hydroxylation ; rat ; guinea pig ; 6-n-propylchromone-2-carboxylic acid ; Mosher's esters ; 1H-NMR configurational assignment ; 19F-NMR configurational assignment ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Following administration of 6-n-propylchromone-2-carboxylic acid (6-n-PCCA) (500 μmol/kg) to male rats, three metabolic products were detected and isolated from the 0-24 h urine. All were identified as resulting from oxidation exclusively along the 6-n-propyl moiety. Some 66% of the dose was excreted in the 0-24 h urine, 55% of which was 6-PCCA, with 15% as (6-1′-hydroxypropyl)chromone-2-carboxylic acid (6-1′-HPCCA), 22% as 6-(2′-hydroxypropyl)chromone-2-carboxylic acid (6-2′-HPCCA), and 4% as (6-3′-carboxypropyl)chromone-2-carboxylic acid (6-3′-CPCCA). Derivatization of the methyl esters of the hydroxylated metabolities with S-α-methoxy-α-(trifuloromethyl)-phenylacetyl chloride (Mosher's reagent) allowed the evaluation of urinary enantiomeric composition by HPLC and assignment of their absolute configurations by NMR. This was found to be 90:10 (R/S) for 6-2′-HPCCA, and 7:93 (R/S) for 6-1′-HPCCA. When rats were dosed with the racemic 1′- and 2-hydroxy metabolites; no stereoselective metabolism or excretion was observed. Administration of 6-n-PCCA to male guinea pigs revealed that this species was unable to metabolise this compound. © 1993 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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  • 15
    ISSN: 0899-0042
    Keywords: chiral HPLC ; solvent effect ; quantitative substituent effects ; molecular recognition mechanism ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A two level full factorial design has been applied to quantify the effect of three selected structural parameters on the capacity factors and chiral separation of atropisomers in N-arylthiazoline-2-(thi)-ones derivatives on tris(p-methylbenzoyl) cellulose beads. The behavior of the two enantiomers is influenced by different factors which might result from different retention sites within the same stationary phase. It appears that the two enantiomers behave independently on the CSP, the order of elution and separation being controlled by a minor steric modification in a very precise location in the molecule for one enantiomer. The methodology of the experimental design allows the comparison of equations generated from data issued from designed compounds. These equations afford much more information than the step by step comparison of individual molecules. In our case, the tris(p-methylbenzoyl)cellulose beads and microcrystalline cellulose triacetate appear as complementary CSPs for the resolution of atropisomers of the series studied. © 1993 Wiley-Liss, Inc.
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  • 16
    ISSN: 0899-0042
    Keywords: enantiomer resolution ; gas chromatography ; Chirasil-Val ; alcohol ; basic compounds ; imidazole ; chiral discrimination ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The direct resolution of enantiomers of a series of imidazol-2-yl-substituted alcohols has been achieved by gas chromatography on a well-deactivated fused-silica capillary column, coated with L-Chirasil-Val as the chiral stationary phase. The separation of these basic compounds is accomplished without exaggerated peak tailing. Compared to simpler alcohols the resolution factors (α) observed are extraordinarily large. While the imidazolyl substituent may contribute to the mechanism of the chiral discrimination, the crucial interaction is assumed to be through the hydroxy group, based on the observation that the resolution factors for the corresponding O-acetyl derivatives are markedly reduced. © 1993 Wiley-Liss, Inc.
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  • 17
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 241-245 
    ISSN: 0899-0042
    Keywords: chiral counterion ; reversed-phase chiral ion-pair chromatography ; diastereomeric ion-pairs ; chiral mobile phase additive ; (-)-2,3:4,6,-di-O-isopropylidene-2-keto-L-gulonic acid ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The direct separation of enantiomeric amines has been carried out using a chiral counter ion, (-)-2,3:4,6,-di-O-isopropylidene-2-keto-L-gulonic acid [(-)-DIKGA] dissolved in polar mobile phases, water:methanol or isopropanol:acetonitrile. High separation factors, α = 1.2-1.7, were obtained for several compounds of pharmacological interest such as metoprolol, oxprenolol, remoxipride, mefloquine and p-OH-ephedrine. © 1993 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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  • 18
    ISSN: 0899-0042
    Keywords: cellulose tris(3,5-dimethylphenyl carbamate) ; cellulose tribenzoate ; chiral HPLC ; enantiomers ; temperature dependence ; chiral recognition ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Chiral chromatography on cellulose tris(3,5-dimethylphenyl carbamate) (Chiralcel OD) and cellulose tribenzoate (Chiralcel OB) coated stationary phases has been successfully used for the optical resolution of rac-(thio)glycidyl esters (acetate, propionate, butyrate). Glycidyl esters could sufficiently be resolved on the OD column whereas for the thio analogues baseline resolution is obtained on CSP OB using hexane/2-propanol mobile phases. The separation factor (α) and resolution (RS) depend on column temperature, eluent composition, and flow rate, respectively. Best results were obtained for the butyrates and at low temperatures in general. © 1993 Wiley-Liss, Inc.
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  • 19
    ISSN: 0899-0042
    Keywords: simulated moving bed technology ; chiral separation ; cellulose triacetate ; preparative scale liquid chromatography ; racemic epoxide ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The feasibility of using simulated moving bed technology (SMB) for chiral separation on cellulose triacetate is demonstrated on the preparative scale: 1 kg of a chiral epoxide has been separated. On comparing SMB technology with conventional liquid chromatography it turns out that the main advantage of SMB lies in the significant reduction of mobile phase consumption. The process design for SMB is made theoretically and the predictions are confirmed by our pilot study. © 1993 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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  • 20
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 282-287 
    ISSN: 0899-0042
    Keywords: phenoxyl radicals ; hydrogen bond ; host guest interactions ; diastereomers ; absolute configuration ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Chiral recognition with magnetic methods requires the formation of diastereomers. Due to the variety of appropriate reactions, hydrogen bond formation, esterification, and acetalization as well as host-guest interactions were chosen for basic investigations. The results obtained indicate that in the case of diamagnetic compounds the chemical shifts and for paramagnetic compounds the β-proton coupling constants are the most useful parameters. By combination of both pieces of information, assignment of the absolute configuration was achieved. © 1993 Wiley-Liss, Inc.
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  • 21
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. iv 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 22
    ISSN: 0899-0042
    Keywords: chromatography ; chiral stationary phases ; separation of enantiomers ; CD spectra ; C4 and C2 symmetry ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Various possibilities to obtain intrinsically chiral calix[4]arenes are discussed. The enantiomers of three 1,3-dietheresters and one monoether compound derived from dissymmetric calix[4]arenes with C4 symmetry were separated by HPLC using chiral stationary phases and characterized by their CD spectra. © 1993 Wiley-Liss, Inc.
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  • 23
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 315-319 
    ISSN: 0899-0042
    Keywords: chiral selectors ; natural product derived hosts ; optically active hosts ; clathrate hosts ; bulky 1,2-diols ; inclusion compounds ; host-guest complexes ; chiroselective cocrystallization ; chiroselective vapor sorption ; preparative scale enantioseparation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: New optically active host compounds for chiroselective crystalline inclusion formation derived from natural lactic acid are synthesized. They enable useful enantiomer separations of different chiral compounds via cocrystallization and sorption on preparative scale including various ketones, lactones, alcohols, sulfoxides, and methyloxiranes. In the cases of 3-methylcyclohexanone, 4-methyl-δ-valerolactone, and 2-phenylpropanol, ees 〉 99% were obtained from one cocrystallization step using these hosts. © 1993 Wiley-Liss, Inc.
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  • 24
    ISSN: 0899-0042
    Keywords: stereoselective protein binding ; chiral liquid chromatography ; human serum albumin ; α1-acid glycoprotein ; anticoagulant ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Stereoselectivities for the binding of rac-acenocoumarol to human serum albumin (HSA), α1-acid glycoprotein (AGP), and human plasma were determined by chiral HPLC analysis of the ultrafiltrates on a Chiral-AGP column. The results confirmed the previously detected inverse stereoselectivities; for HSA the ratio of the enantiomeric constants was KR/KS ∼ 2, while for AGP it was KR/KS ∼ 0.3. In plasma the contribution of HSA dominates, although in pathological states, elevated AGP levels may compensate for stereoselective distribution. © 1993 Wiley-Liss, Inc.
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  • 25
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 238-240 
    ISSN: 0899-0042
    Keywords: chiral HPLC ; Chiralcel OD ; Chiralcel OD-R ; guaifenesin ; methocarbamol ; dextromethorphan ; levomethorphan ; racemorphan ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: HPLC chiral separations on silica gel coated with derivatized cellulose stationary phases are described. Most examples make use of the Chiralcel OD column from Daicel, Inc. With a judiciously chosen mobile phase, baseline separations of the enantiomers can be achieved. If those separations are used as a base for enantiomeric purity determination, detectable limits of 0.1% of the minor enantiomer are routinely accessible. Examples are given concerning separations of guaifenesin, methocarbamol, and racemorphan. © 1993 Wiley-Liss, Inc.
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  • 26
    ISSN: 0899-0042
    Keywords: enzymic kinetic resolution ; porcine pancreatic lipase (PPL) ; hydrolysis ; transesterification ; acylation ; enol esters ; chiral HPLC ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Both hitherto unknown (+)-(R)- and (-)-(S)-thioglycidyl esters, (R)-(2) and (S)-(2), have been synthesized with different high enantiomeric excesses (ee) by two routes from the corresponding rac-glycidyl esters rac-(1). The first includes a porcine pancreatic lipase (PPL)-mediated kinetic resolution of these esters followed by sulfuration with practically complete inversion to the (+)-(R)-enantiomer (+)-(R)-(2) (36-86% ee). (-)-(S)-Thioglycidyl esters (-)-(S)-(2) are obtained by the reverse reaction sequence (43-80% ee). In the latter case the hydrolysis rate is lower than that of analogous glycidyl esters. Moreover, the dependence of enantiomeric excess on the size of the acyl-group is of the opposite tendency. Therefore, in both cases suitable selection of the acid residue gives rise to maximum enantioselectivity. The irreversible lipase-catalyzed acylation of rac-glycidol and rac-thioglycidol, however, was found to be a less suitable alternative. The enantiomeric excess of recovered homochiral esters was determined by chiral chromatography using modified cellulose stationary phases (OB, OD). © 1993 Wiley-Liss, Inc.
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  • 27
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 277-281 
    ISSN: 0899-0042
    Keywords: anomalous dispersion ; absolute structure ; enantiomer determination ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The paper discusses several feasibility prediction criteria with particular emphasis on light atom molecules. For several examples of refined absolute structures, feasibility predictions are calculated and compared with a posteriori calculated values of the Bijvoet ratio. An extension of the Pathasarathy table of the expected value of the Bijvoet ratio is given for parameter ranges corresponding to light anomalous scatters. Practical conclusions are drawn for absolute structure determination of compounds containing oxygen or nitrogen as anomalous scatterers. © 1993 Wiley-Liss, Inc.
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  • 28
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    Chirality 5 (1993), S. 293-293 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 29
    ISSN: 0899-0042
    Keywords: calcium channel blockers ; enantiomers ; stereoselectivity ; solubilization ; enantiomeric resolution ; stereodifferential complexation ; 1H-NMR chiral recognition ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Structure-interaction relationships, stereoselectivity, and solubility enhancement in inclusion compexation of β-cyclodextrins (CDs) with some racemic and enantiomerically pure 1,4-dihydropyridine derivatives (DHPs) were investigated. 1:1 and 1:2 (mole ratio) complexes were prepared and characterized by X-ray powder diffraction, differential scanning calorimetry (DSC), MS-FAB spectrometry, 1H-NMR spectroscopy, water and phase solubility. The solubility studies have revealed different complexation equilibria for optically pure DHP enantiomers, and corresponding racemic mixtures in water solutions. By means of 1H-NMR chemical shift measurements, the inclusion of aromatic fragments of racemic and enantiomerically pure DHP molecules within the cavities of different CDs was elucidated. Considerable stereoselectivity in complexation interactions was observed. The results indicate the potential use of cyclodextrins as chiral selectors for enantiomeric resolution of 1,4-DHP calcium antagonists. © 1993 Wiley-Liss, Inc.
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  • 30
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    Chirality 5 (1993), S. 295-299 
    ISSN: 0899-0042
    Keywords: enantiomers ; BSA ; N-alkanoyl-leucines ; chiral recognition ; radiolabeling ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In order to get further insight into the mechanism by which bovine serum albumin (BSA) discriminates between enantiomers of organic acids, some radioisotopically labeled, nonaromatic carboxylic acids were studied under varying mobile phase conditions. It was found for a series of N-alkanoyl-DL-[3H]leucines that the D-enantiomers were much more strongly retained and that the composition of the mobile phase could be adjusted to give very large (α 〉 20) enantiomeric separation factors. The elution order was consistent with what has been found earlier for other N-acyl derivatives as well as for N-arylcarbamoyl derivatives of simple aliphatic amino acids. A marked increase in the hydrophobic interaction of the D-enantiomers with the chiral phase was found upon a lowering of the mobile phase strength, conditions under which the L-form was only slightly influenced. These and other results are consistent with a chiral recognition model by which inclusion of the compound in a hydrophobic chiral cavity of BSA with simultaneous charge interaction is assumed to take place and whereby discrimination is determined by the steric bulk and orientation of the α-substituent. © 1993 Wiley-Liss, Inc.
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  • 31
    ISSN: 0899-0042
    Keywords: chiral Lewis acid ; sequential transformations ; domino reaction ; intramolecular hetero-Diels-Alder reaction ; enantioselective cycloadditions ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Enantioselective reaction of the aldehydes 1a-g and the 1,3-dicarbonyl compound 2 in the presence of the chiral Lewis acid 5, derived from diacetone glucose, leads in a sequential transformation consisting of a Knoevenagel condensation and an intramolecular Diels Alder reaction to the cycloadducts 4a-g with an ee value up to 88%. The selectivity is strongly dependent upon the temperature and solvent giving best results at room temperature in isodurene; in agreement with the principle of isoinversion, the ee values decrease at lower and higher temperatures. © 1993 Wiley-Liss, Inc.
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  • 32
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    Chirality 5 (1993), S. 479-482 
    ISSN: 0899-0042
    Keywords: chiral resolution ; high-performance liquid chromatography (HPLC) ; β-blocker ; cellulose ; Tris-3,5-dimethylphenylcarbamate ; chiral stationary phase ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The simultaneous determination of the enantiomers of the β1-selective adrenergic antagonist atenolol in human plasma and urine is described. After an alkaline preextraction atenolol is extracted from biological material at pH 12.3 using dichloromethane/propan-2-ol. The separation of the underivatized enantiomers is achieved by high-performance liquid chromatography on a chiral stationary phase (Chiralcel OD, cellulose tris-3, 5-dimethylphenylcarbamate, coated on silica gel) with fluorimetric detection. (-)-(S)-Pindolol is used as an internal standard. The detection limits of 5 ng/ml enantiomer in plasma and 50 ng/ml enantiomer in urine are sufficient for pharmacokinetic studies after therapeutic doses. © 1993 Wiley-Liss, Inc.
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  • 33
    ISSN: 0899-0042
    Keywords: continuous bed ; chiral phase ; cellulase ; enantiomers ; HPLC ; β-blockers ; propranolol ; alprenolol ; metoprolol ; labitolol ; practolol ; pindolol ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Columns prepared by coupling cellulase as a chiral selector to silica beads are very efficient for the separation of enantiomers. In this paper we show that continuous polymer beds compete favorably with silica beads as chromatographic supports for such separations. The chiral stationary phase is prepared either by entrapment in and simultaneous covalent linkage of ally1 cellulase to the continuous beds during their preparation or by covalent immobilization of cellulase on an epoxy-activated continuous bed. Enantiomers of β-blockers were separated rapidly and with high resolution. The enantiomers of practolol were thus baseline resolved within 45 sec. The recognition center-or at least part of it - coincides with the active center of the enzyme, since the enantiomers could not be separated in the presence of the competitive enzyme inhibitors cellobiose and D-glucose and the separation was also impaired upon addition of the substrate carboxymethyl cellulose to the eluent. Similar observations have been reported for silica columns derivatized with cellulase. The capacity factor and the separation selectivity could be tuned by the pH and the concentration of the mobile phase, a phosphate buffer. No modifier was required, as is sometimes the case with silica-based supports. The continuous beds give faster enantiomer separations than do columns of silica and are more pH-stable and cost effective to prepare. © 1993 Wiley-Liss, Inc.
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  • 34
    ISSN: 0899-0042
    Keywords: diborane and sodium borohydride reduction ; diastereomeric amino alcohols ; Swern oxidation ; antitetrabenazine activity ; biogenic amine uptake inhibition ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The synthesis of the enantiomers of bupropion, (rac)-2-tert-butylamino-3′-chloropropiophenone 1 (Wellbutrin®) is described. The enantiomers were compared with the racemate in both the tetrabenazine-induced sedation model and the inhibition of uptake of biogenic amine assay. No significant differences were found in their potencies to reverse tetrabenazine-induced sedation in mice or in their IC50 values as inhibitors of biogenic amine uptake into nerve endings obtained from mouse brain. © 1993 Wiley-Liss, Inc.
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  • 35
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    Chirality 5 (1993), S. 516-526 
    ISSN: 0899-0042
    Keywords: chiral ; cyclodextrin ; drug ; electrophoresis ; micellar electrokinetic ; resolution ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: High-performance capillary electrophoresis (HPCE) and micellar electrokinetic capillary chromatography (MECC) were applied to the resolution of racemic nonsteroidal antiaromatase drugs and intermediates. Successful results were obtained in both modes using α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), or 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD) as chiral selectors. Depending on the structure of the solute, one of the cyclodextrins was generally better suited for resolution of the racemate. The basic solutes were analyzed under HPCE conditions, whereas the nonionizable compounds such as glutethimide (Doriden®) were analyzed in MECC mode. For the azole-type antiaromatase Fadrozole, both HPCE and MECC modes could be used to achieve the separation of the enantiomers. The influence of experimental factors such as pH, the presence of organic modifier, temperature, the micelle concentration, and the concentration of the chiral selector is also discussed on the basis of the results obtained with some chiral barbiturates. The possibility of analyzing the enantiomers directly in plasma samples was also demonstrated. © 1993 Wiley-Liss, Inc.
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  • 36
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    Chirality 5 (1993), S. 596-601 
    ISSN: 0899-0042
    Keywords: microbial metabolism ; chiral inversion ; chiral inversion of 2-phenylpropionic acid ; oxidation of ibuprofen ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The metabolism of (R,S)-ibuprofen has been investigated in 24 microbial cultures. Of these Cunninghamella elegans, Mucor hiemalis, and Verticillium lecanii catalyzed the oxidation of the drug to 2-[4-(2-hydroxy-2-methylpropyl)phenyl]propionic acid, a known mammalian metabolite. The extent of metabolism was greatest with V. lecanii, with some 47% of the substrate being consumed over a 7-day incubation period. Enantiomeric analysis indicated stereoselective metabolism of (R)-ibuprofen, the enantiomeric composition of the residual substrate being R/S = 0.25. Following a preparative scale incubation of (R,S)-ibuprofen with V. lecanii, in which the reaction was allowed to go to completion, the metabolite was found to be predominantly of the S-configuration (S/R = 2.1), suggesting that chiral inversion of either the drug and/or the metabolite had taken place. Analysis of extracts following incubation of (R,S)-, (R)-, and (S)-2-phenylpropionic acid with V. lecanii, for 21 days, indicated that chiral inversion of the (R)-enantiomer to its optical antipode had taken place. The results of these investigations indicate that microorganisms, in addition to mammals, are able to mediate the chiral inversion of 2-arylpropionic acids. This observation may have implications for the preparation of optically pure 2-arylpropionic acids. © 1993 Wiley-Liss, Inc.
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  • 37
    ISSN: 0899-0042
    Keywords: NSAIDs ; enantioselectivity ; prostaglandin E2 ; thromboxane B2 ; HUVEC ; PMN ; keratinocytes ; P388D1 ; platelets ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The pharmacological activity of rac-ketoprofen and its enantiomers was investigated in vitro using different cellular models. The effect of these compounds on arachidonic acid metabolism was assessed by measuring the inhibition of prostanoid generation under the action of several agonists. Thus, we have evaluated the inhibition of (1) thromboxane B2 synthesis in rabbit platelets and human polymorphonuclear leukocytes (PMNs), (2) prostaglandin E2 synthesis in three cultured cells, namely human umbilical vein endothelial cells (HUVEC), human keratinocytes, and mouse macrophage-like P388D1 cells. The IC50 values found for (+)-(S)-ketoprofen were in the range between 0.1 nM and 0.8 μM, being slightly lower in all models than those found for rac-ketoprofen (0.4 nM-3 μM). On the other hand, (-)-(R)-ketoprofen showed inhibition of cyclooxygenase only at concentrations two or three orders of magnitude higher than those required for the (+)-(S) enantiomer. These results, obtained with cell types of relevance for inflammatory processes and with compounds of high optical purity, demonstrate that the prostanoid biosynthesis inhibition caused by the drug rac-ketoprofen is exclusively due to its dextrorotatory enantiomer. © 1993 Wiley-Liss, Inc.
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  • 38
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    Chirality 5 (1993), S. 616-621 
    ISSN: 0899-0042
    Keywords: cellulose tris(4-isopropoxyphenylcarbamate) ; cellulose tris(3,5-dimethyl-4-methoxyphenylcarbamate) ; amylose tris(3,5-dimethyl-4-methoxyphenylcarbamate) ; optical resolution ; HPLC ; chiral stationary phase ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Ten phenylcarbamate derivatives of cellulose and amylose having alkoxy groups such as ethoxy, isopropoxy, and isobutoxy at 4-position, and methyl groups at 3- and 5-positions and methoxy group at 4-position were synthesized and their chiral recognition abilities as stationary phases for high-performance liquid chromatography were investigated and compared to those with tris(4-methoxyphenylcarbamate)s of cellulose and amylose. In 4-alkoxy derivatives of cellulose, chiral recognition ability increased as the bulkiness of 4-alkoxy groups increased. 4-Isopropoxy and 4-isobutoxy derivatives showed high chiral recognition. On the other hand, chiral discrimination of amylose 4-alkoxy derivatives scarcely depended on the bulkiness of the alkoxy group, and 4-methoxy and 4-isopropoxy derivatives showed high chiral recognition. 3,5-Dimethyl-4-methoxyphenylcarbamates of cellulose and amylose possessed higher chiral recognition ability than the corresponding 4-methoxy derivatives. © 1993 Wiley-Liss, Inc.
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  • 39
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 40
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    Chirality 5 (1993), S. 58-60 
    ISSN: 0899-0042
    Keywords: menthol ; nasal delivery ; adverse effects ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: It is shown, using in vitro measurements of beat frequency of rat tracheal cilia, that (+)-(1S, 2R, 5S)-menthol and (-)-(1R, 2S, 5R)-menthol have equipotent ciliotoxicities despite the fact that inhalation of menthol vapours from the crystals of the pure enantiomers show clearly that the (-)-(1R, 2S, 5R)-menthol produces a more potent cooling sensation. Differential scanning calorimetry demonstrates the formation of a racemic compound when equimolar amounts of the two enantiomers are admixed. © 1993 Wiley-Liss, Inc.
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  • 41
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    Chirality 5 (1993), S. 84-90 
    ISSN: 0899-0042
    Keywords: in vitro dissolution ; enantioselective ; enantiomers ; bioequivalency ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The stereoselectivity of the in vitro dissolution of two commercially available sustained release formulations of rac-verapamil (rac-VER) has been investigated. The studies were carried out using a single-tablet continuous-flow apparatus and the concentrations of R- and S-VER released from the formulations were measured using enantioselective chromatography on a high performance liquid chromatography (HPLC) chiral stationary phase containing immobilized α1-acid glycoprotein (Chiral AGP-column). The data from this study demonstrates that the two formulations have different dissolution profiles and that the amount of drug dissolved was highly dependent on pH. In addition, between pH 3 and 8, the total cumulative amount of R-VER released was greater than the amount of S-VER and a statistically significant difference (P 〈 0.01) was detected at pH 6. The results of this study indicate that bioavailability and bioequivalency studies should consider the possibility of enantioselective dissolution when racemic compounds are present in the formulations. © 1993 Wiley-Liss, Inc.
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  • 42
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    Chirality 5 (1993), S. 91-96 
    ISSN: 0899-0042
    Keywords: 1,4-benzodiazepines ; oxazepam ; 3-O-methyloxazepam ; stereoselective nucleophilic substitution ; kinetics ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: pKa1 values of 3-methoxy-N-desmethyldiazepam in acetonitrile and methanol containing various acid concentrations were determined by spectrophotometry to be 3.5 and 1.3, respectively. Temperature-dependent racemization of enantiomeric 3-methoxy-N-desmethyldiazepam in methanol containing 0.5 M H2SO4 was studied by circular dichroism spectropolorimetry and the racemization reactions were found to follow apparent first-order kinetics. Thermodynamic parameters of the racemization reaction were found to be: Eact = 18.8 kcal/mol, and at 25°C: ΔH
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  • 43
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    Chirality 5 (1993), S. 97-101 
    ISSN: 0899-0042
    Keywords: 1,3-oxathiolane ; chiral α-methylbenzylamine ; optical resolution ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: cis- and trans-5-Ethoxy-1,3-oxathiolane-2-carboxylic acids were obtained in pure form. The cis isomer was resolved into its enantiomers through diastereoisomeric salt formation with enantiomerically pure α-methylbenzylamine. Reduction of the salt followed by benzoylation led to 2-benzoyloxymethyl-5-ethoxy-2(R)-5(S)-1,3-oxathiolane and 2-benzoyloxymethyl-5-ethoxy-2(S)-5(R)-1,3-oxathiolane, useful intermediates in nucleoside chemistry. © 1993 Wiley-Liss, Inc.
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  • 44
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    Chirality 5 (1993), S. 105-111 
    ISSN: 0899-0042
    Keywords: enantiomers ; racemization ; epimers ; epimerization ; configurational stability ; nonenzymatic reactions ; oxazepam ; amfepramone ; thalidomide ; atropine ; chlorthalidone ; pilocarpine ; 16α-substituted 3-methoxyestrones ; chlorpromazine ; telenzepine ; tofisopam ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A variety of reactions can be categorized under the global concept of the “interconversion of stereoisomers.” Thus, racemization or epimerization can result from inversion of labile chiral centers. From the examples available, some predictive rules are suggested for a chiral center of the type R″R′RC—H undergoing base-catalyzed inversion and a provisional table of affecting groups is presented. Unimolecular inversion of nonsymmetrical, nonplanar ring systems can also result in racemization or epimerization, but no generalization can yet be offered. Beside these cases of nonenzymatic reactions, a limited variety of enzymatic reactions can operate to interconvert stereoisomers, the outcome rarely being a racemic mixture. An important aspect of stereoisomer interconversion is the time scale in which the phenomenon is observed. Thus, several reactions to nonezymatic racemization or epimerization are fast compared to the duration of action of the drug and therefore have pharmacological significance, while other are slower and are of pharmaceutical relevance only. © 1993 Wiley-Liss, Inc.
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  • 45
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    Chirality 5 (1993), S. 120-125 
    ISSN: 0899-0042
    Keywords: beclobrate ; beclobric acid ; acyl glucuronides ; hydrolysis ; isomerization ; irreversible binding ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Acyl glucuronides are known to be labile conjugates, which undergo hydrolysis and bind irreversibly to proteins. The lipid-regulating agent (±)-beclobrate is immediately converted to the free acid after oral administration. Further metabolism leads to formation of the corresponding diastereomeric acyl glucuronides. Beclobric acid glucuronides were quantified by indirect measurement with an HPLC method based on chiral fluorescent derivatization of the carboxylic acid and subsequent normal-phase chromatography. The renal clearance of unchanged drug is low, with almost all drug excreted into urine as glucuronic acid conjugates. Beclobric acid glucuronide is also detectable in plasma. In vitro degradation studies with beclobric acid glucuronide (at a concentration of 5 μM in 150 mM phosphate buffer pH 7.4) exhibited a minor tendency for acyl migration and hydrolysis, i.e., a higher stability than has been observed for the acyl glucuronides of most other drugs. The in vitro degradation half-lives of the two beclobric acid β-1-O-acyl glucuronides were 22.7 and 25.7 h. After incubation with pooled plasma and human serum albumin in buffer pH 7.4 irreversible binding was measured in vitro. No significant difference between the two enantiomers was detected with respect to the magnitude of in vitro irreversible binding. In 3 healthy male volunteers the extent of irreversible binding of both beclobric acid enantiomers to plasma proteins was investigated after single and multiple oral doses of racemic beclobrate (100 mg once daily). Irreversible binding of both enantiomers was observed in all volunteers. The adduct densities for (-)- and (+)-beclobric acid after single 100 mg beclobrate doses were 0.147 × 10-4 and 0.177 × 10-4 mol/mol protein. Multipie dosing increased irreversible binding 3- to 4-fold. © 1993 Wiley-Liss, Inc.
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  • 46
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    Chirality 5 (1993), S. 143-149 
    ISSN: 0899-0042
    Keywords: 31P NMR of chymotrypsin adducts ; serine protease adducts ; phosphonate ester-chymotrypsin adducts ; organophosphorus adducts of serine proteases ; diastereomeric serine protease adducts ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Generation of diastereomeric phosphonate ester adducts of chymotrypsin was evidenced for the first time by 31P NMR and spectrophotometric kinetic measurements. 31P NMR signals were recorded for 4-nitrophenyl 2-propyl methylphosphonate (IMN) at 32.2 ppm and for its hydrolysis product at 26.3 ppm downfield from phosphoric acid. The inhibition of α-chymotrypsin at pH 〉 8.0 by the faster reacting enantiomer of IMN or 2-propyl methylphosphonochloridate (IMCl), or other phosphonate ester analogs of these compounds, all caused a ∼6.0 ppm downfield shift of the 31P signal to the 39-40 ppm region. IMN, when applied below the stoichiometric amount of chymotrypsin, under the same conditions, generated two signals, at 39.0 and at 37.4 ppm. Scans accumulated in hourly intervals showed the decomposition of both diastereomers, with approximate half-lives of 12 h at pH 8.0 and 22°C, into a species with a resonance at 35.5 ppm. The most likely reaction to account for the appearance of this new peak is the enzymic dealkylation of the isopropyl group from the covalently bound phosphonate ester. We base this conclusion mostly on the similarity of the upfield shift to the hydrolysis of phosphonate esters. Contrary to experience with phosphate ester adducts of serine proteases, no signal was detected higher than 25.0 ppm downfield from phosphoric acid for several phosphonate ester adducts of chymotrypsin and in no case did the resonance for the adduct shift further downfield in the course of the experiments. © 1993 Wiley-Liss, Inc.
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  • 47
    ISSN: 0899-0042
    Keywords: (S)-naphthylurea chiral stationary phase ; subcritical fluid chromatography ; supercritical fluid chromatography ; antimalarial agents ; enantiomeric separations ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The behavior of mefloquine, halofantrine, enpiroline, quinine, quinidine, chloroquine and primaquine is studied by subcritical fluid chromatography on a (S)-naphthylurea column (250 mm × 4.6 mm ID) with a subcritical mobile phase composed of carbon dioxide, methanol and triethylamine (flow rate of 3 ml/min). Except for primaquine and chloroquine, each enantiomer was separated at a temperature between 40 and 60°C, and at a pressure below 15 MPa. A 98/2, v/v CO2/methanol 0.1% triethylamine mixture allowed the separation of halofantrine enantiomers while the enantiomers of the more polar metabolite (N-desbutylhalofantrine) were separated with a 80-20 v/v mixture as used for mefloquine, enpiroline, quinine and quinidine. The influence of temperature, pressure and of the nature of the mobile phase is discussed. © 1993 Wiley-Liss, Inc.
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  • 48
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    Chirality 5 (1993), S. 199-199 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 49
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    Chirality 5 (1993), S. 201-206 
    ISSN: 0899-0042
    Keywords: enantiomer ; racemates ; separations ; chiral homology ; synergism ; push/pull model ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A new “push/pull” model has been developed to explain synergistic effects observed in a system in which a chiral stationary phase (CSP) is used in combination with its homologous chiral mobile phase additive (CMPA). The model predicts the beneficial CMPA enantiomer and the counterproductive CMPA enantiomer a priori. Thus, an (R)-CSP will obtain positive synergism from a homologous (S)-CMPA and negative synergism from a homologous (R)-CMPA. The reverse is true for an (S)-CSP. The importance of structural homology between the CSP and the CMPA is demonstrated. Furthermore, the analysis time is decreased relative to the use of a CSP alone, because the retention time of the analyte peaks decreases when the CMPAs are used. © 1993 Wiley-Liss, Inc.
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  • 50
    ISSN: 0899-0042
    Keywords: hydroxypropyl-β-cyclodextrin ; cyclodextrin ; polarimetric detection ; optical rotation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A high-performance liquid chromatographic (HPLC) method has been developed for separation and determination of components in hydroxypropyl-β-cyclodextrin (HP-β-CD). The method involves separation on an amino-bonded HPLC column using water-acetonitrile as a mobile phase with a polarimetric HPLC detector for quantification. It provides good selectivity and sensitivity and can also be used to compare different sources of HP-β-CD and to measure batch to batch variation. The similarity of the values of molar optical rotation for β-cyclodextrin (β-CD) and HP-β-CD suggests that a polarimetric HPLC detector may be used with a straightforward area normalization method, to quantify the proportion of β-CD in any HP-β-CD sample. Trace amounts of β-CD in HP-β-CD have been measured to a precision of 0.01%. © 1993 Wiley-Liss, Inc.
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  • 51
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    Chirality 5 (1993), S. 232-237 
    ISSN: 0899-0042
    Keywords: enantiomer ; supercritical fluid chromatography (SFC) ; gas chromatography (GC) ; resolution ; polymer ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The application of cellulose-based stationary phases for chiral separations has been extended to open tubular column chromatography. Efficient columns were obtained by coating the capillaries with mixtures of chiral cellulose materials and conventional achiral stationary phases for gas chromatography. In this study, various siloxane and polyethylene glycol polymers were used as achiral components and mixed with different substituted benzoylcellulose derivatives as chiral components. Systematic investigations were carried out to determine the optimal ratio for the components of the stationary phase. Depending on the chromatographic mode - gas chromatography (GC) or supercritical fluid chromatography (SFC) - the stationary phases were found to behave differently. The applicability of the technique was demonstrated by the resolution of various racemic compounds. © 1993 Wiley-Liss, Inc.
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  • 52
    ISSN: 0899-0042
    Keywords: enantiomers ; countercurrent gas-liquid chromatography ; preparative separation ; amino acid derivatives ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Preparative separation of derivatives of amino acid enantiomers was carried out by a countercurrent gas-liquid chromatography (CCGLC) with chiral liquid phases, N-stearoyl-L-valine tert-butylamide and/or N-stearoyl-L-leucine tert-butylamide. In order to make effective use of these phases and also to lower the viscosity, Apiezon C was added as diluent. Through a repeated operation of a temperature gradient, purities more than 99% of leucine and α-amino butyric acid derivatives were proved to be obtained. © 1993 Wiley-Liss, Inc.
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  • 53
    ISSN: 0899-0042
    Keywords: β-cyclodextrin ; enantiomeric separation ; pH effects ; ionic strength effects ; flow rate effects ; solvent selectivity ; optimization ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The goal of this work is to investigate the direct chromatographic separation of the enantiomers of fluoxetine and its active metabolite norfluoxetine. The liquid chromatographic retention behavior of these enantiomers on a β-cyclodextrin bonded-phase column was investigated with respect to mobile phase composition, pH, ionic strength, and solvent selectivity. Relationships were established between these factors and the three most important chromatographic parameters: retention time, resolution, and selectivity. Most of the evidence suggests that the unique selectivity of this column isdue to inclusion complex formation, which provides the physical basis for enantiomeric resolution. After these studies a set of optimum chromatographic conditions was chosen for the simultaneous separation/determination of a mixture of the four enantiomers using fluorescence detector. © 1993 Wiley-Liss, Inc.
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  • 54
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    Chirality 5 (1993), S. 272-276 
    ISSN: 0899-0042
    Keywords: chirality ; helical stereochemistry ; la coupe du roi ; chiral recognition ; chiral polysectioning ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Oligo(bipyridine) strands and Cu(I)/Ag(I) form duplexes having a 21-screw coincidental with a C2-axis. A segment containing a complete turn of the duplex can be considered to be a coupe du roi ensemble of two homochiral strands. Moreover, for D2d symmetry monocationic Cu(I) complexes of bipyridine trimers and pentamers, addition of the requisite Cu(I) cations is a true chemical example of la coupe du roi. In this reaction, an achiral monocationic complex is converted into a multiple-cationic duplex of two homochiral and homotopic 21-helical halves. The chirality of the resulting duplex is a function of the particular set of bipyridine enantiotopic faces which are used for binding the additional cations. © 1993 Wiley-Liss, Inc.
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  • 55
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    Chirality 5 (1993) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 56
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    Chirality 5 (1993), S. 300-302 
    ISSN: 0899-0042
    Keywords: chiral separation ; α1-acid glycoprotein (AGP) ; nornicotine ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A sensitive and reproducible HPLC method utilizing a commercially available chiral α1-acid glycoprotein (AGP) phase has been developed to separate and quantify the enantiomers of nicotine. The method is suitable for routine use as indicated by column life. The quantification of (R/S:0.05/99.95)-nicotine or (R/S:99/1)-nicotine was possible. In addition, the separation or at least partial separation of the enantiomers of nornicotine and nornicotine-derived compounds was achieved. © 1993 Wiley-Liss, Inc.
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  • 57
    ISSN: 0899-0042
    Keywords: chiral stationary phase ; mobile phase modifier ; digoxin ; warfarin ; medium chain fatty acid ; bilirubin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Specific ligand markers for the various binding sites of human serum albumin (HSA) have been described in the literature. Some of these markers (medium chain fatty acids, warfarin, digoxin, and bilirubin) were used as mobile phase modifiers. Using a high performance liquid chromatographic (HPLC) column containing HSA as stationary phase, their influence was investigated on the separation in this phase of the enantiomers of three benzodiazepines (temazepam, oxazepam, and lorazepam). Displacement effects were observed with medium chain fatty acids. This influence was proportional to the chain length and to the concentration of acid. Allosteric cooperative effects were noted with digoxin for the three benzodiazepines. Both displacement and cooperative effects were observed with warfarin. Stereoselectivity was decreased for temazepam and oxazepam and increased for lorazepam. © 1993 Wiley-Liss, Inc.
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  • 58
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    Chirality 5 (1993), S. 102-102 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 59
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    Chirality 5 (1993), S. 104-104 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 60
    ISSN: 0899-0042
    Keywords: NSAID ; chirality ; enantiomers ; protein binding ; equilibrium dialysis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Equilibrium dialysis was used to study in vitro the enantioselective binding of R, S, and racemic ketoprofen at physiological pH and temperature in human serum albumin (HSA) (1, 20, and 40 g/liter) and in plasma. The binding of enantiomers in a racemic mixture was studied to see the effect of each isomer on the other's interaction with the protein. The free fractions were determined by high-performance liquid chromatography. The binding of ketoprofen enantiomers to albumin was enantioselective, depending on both drug and protein concentrations. Enantioselectivity was observed in plasma too but was the opposite of that in HSA at 40 g/liter. The percentage of each isomer unbound was higher in the racemic mixture than with the isomer alone. The displacement of probes specific for HSA sites I and II, studied by spectrofluorimetry, suggests that all three preparations of ketoprofen are bound mainly to site I and secondarily to site II. © 1993 Wiley-Liss, Inc.
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  • 61
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    Chirality 5 (1993), S. 150-153 
    ISSN: 0899-0042
    Keywords: aminoacyl adenylate esters ; hydrolytic stabilization by intramolecular interaction ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Studies of the properties of aminoacyl derivatives of 5′-AMP are aimed at understanding the origin of the process of protein synthesis. Aminoacyl (2′,3′) esters of 5′-AMP can serve as models of the 3′-terminus of aminoacyl tRNA. We report here on the relative rates of hydrolysis of AC-D- and L-Phe AMP esters as a function of pH. At all pHs above 3, the rate constant of hydrolysis of the AC-L-Phe ester is 1.7 to 2.1 times that of AC-D-Phe ester. The D-isomer seems partially protected from hydrolysis by a stronger association with the adenine ring of the 5′-AMP. © 1993 Wiley-Liss, Inc.
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  • 62
    ISSN: 0899-0042
    Keywords: enantioselective hydrolysis ; lipase ; esters ; substituent effects ; chiral liquid chromatography ; enantiomer separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In order to make a preliminary study of substituent effects on the rate and enantioselectivity obtained in esterolytic reactions catalyzed by a lipase from Candida rugosa, a series of racemic esters, derived from some α-alkyl and α-halo phenylacetic acids, were prepared. The reactions were studied at pH 6.0 and 50°C under which conditions uncatalyzed hydrolysis was relatively slow. Reaction samples were studied at different points of time by means of analytical chiral reversed-phase liquid chromatography, which permitted the simultaneous determination of product enantiomeric excess and of the degree of total ester hydrolysis. These data were then used to calculate initial rates as well as enantioselectivity. An increase of the steric bulk of the α-substituent was found to highly decrease the rate of the reaction. On the other hand, rates were higher for the p-nitrophenyl esters than for the corresponding 2-chloroethyl esters. Consistently, the enantioselectivity was found to be higher for the latter type of ester. The esters of the α-halo (bromo and chloro) phenylacetic acids gave mandelic acid as the final product. This was caused by a rapid solvolysis of the α-halo phenylacetic acid initially formed. © 1993 Wiley-Liss, Inc.
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  • 63
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    Chirality 5 (1993), S. 168-172 
    ISSN: 0899-0042
    Keywords: chiral stationary phase ; chiral 2-oxetanone ; TLC ; SFC ; preparative LC ; push-pull chromatography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Chiral β-lactones offer an easy and economic approach to novel chiral R- or S-configurated LC phases. The preferred method for their preparation is based on conventional ready-to-use aminopropyl-functionalized silicas, e.g., aminopropyl HPLC columns. The new stationary phases can be used for analytical and preparative separations and are particularly suitable for the resolution of rotatory and heterocyclic stereoisomers. Applications in the LC, SFC, and TLC mode are possible, including the use of β-lactone-based mobile phase additives in a “push-pull” combination. A large variety of organic solvents can be used as eluents. © 1993 Wiley-Liss, Inc.
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  • 64
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    Chirality 5 (1993), S. 181-187 
    ISSN: 0899-0042
    Keywords: enantiomers ; direct separation ; 2-aminotetralins ; dopamine receptor agonist ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 5,6- and 6,7-Dihydroxy-2-aminotetralin (ADTN), racemic dopamine receptor agonists, were resolved into their enantiomers by a new chiral HPLC assay. The separation was performed on a Crownpack CR column, which contains an 18-crown-6-type chiral crown ether as a chiral selector. The chiral recognition is based on the compiexation of the protonated primary amino group and the oxygen atoms inside the cavity of the crown ether. The amino group is attached to the chiral centre and therefore these compounds could be resolved. Mobile phase was perchloric acid pH 2.0 and the detection was UV at 200 nm. Resolution factors were 3.1 for 5,6-ADTN and 1.1 for 6,7-ADTN resulting in very low limits of quantitation (〈0.1%) of the enantiomer present as impurity. Data on the validation of the assay and on the stability of the column are also reported. © 1993 Wiley-Liss, Inc.
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  • 65
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    Chirality 5 (1993), S. 385-392 
    ISSN: 0899-0042
    Keywords: D-amino acids ; bacterial starter cultures ; amino acid racemases ; nutrition ; gas chromatography ; chiral stationary phases ; Chirasil-Val ; Lipodex ; cyclodextrins ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Bacteria of the genera Acetobacter, Bifidobacterium, Brevibacterium, Lactobacillus, Micrococcus, Propionibacterium, and Streptococcus, which are used as so-called starter cultures for the large-scale production of fermented foods and beverages in food biotechnology, have been investigated for the chirality of their amino acids (AA) by gas chromatography (GC). Bacteria were grown in complex media, centrifuged, and washed with 0.85% aqueous NaCl. Aliquots were totally hydrolyzed (6 M HCl, 110°C, 18 h), or extracted with 70% aqueous ethanol in order to isolated free AA. The AA were adsorbed on Dowex WX 8 cation-exchanger, eluted with 4 M ammonia and converted into their N(O)-trifluoroacetyl(TFA) 2-propyl esters or TFA methyl esters. The AA derivatives were investigated by capillary GC using the chiral stationary phases Chirasil-L-Val, Chirasil-D-Val, and Lipodex E. Besides L-AA, in all bacteria D-amino acids (D-AA) were detected; those in the highest relative amounts were D-Ala and D-Asp (occurring in all bacteria) and, in several cases, D-Glu. Lower, but significant amounts of other D-AA such as D-Ser, D-Pro, D-Val, D-Thr, D-Ile, D-Leu, D-Met, D-Phe, D-Tyr, D-Orn, and D-Lys were also detected in certain bacteria. These findings explain the origin of D-AA found in all fermented foods and drinks produced with the aid of bacterial starter cultures. © 1993 Wiley-Liss, Inc.
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  • 66
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    Chirality 5 (1993), S. 407-413 
    ISSN: 0899-0042
    Keywords: stereoselecting ; drug metabolism ; drug interactions ; cytochrome P-45 ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A surprisingly large number of marketed drugs are racemic mixtures. The pharmacokinetic literature on racemic drugs contains a vast amount of information on drug-drug interactions derived from the measurement of total drug concentrations in plasma and urine. The appreciation of the role of stereochemistry in drug interactions with racemic warfarin resulted in a long-overdue scientific rigor being applied to the study of drug interactions. It also compelled us to recognize that much of the literature was uninterpretable. A better understanding of oxidative metabolism, particularly the complexity of the cytochrome P-450 family of enzymes, has also strengthened the scientific basis of drug interactions. We now recognize that investigators and clinicians must consider both stereoselectivity and isozyme selectivity in the study of drug interactions to understand the nature of the interaction so as to more effectively use new and potent drugs. © 1993 Wiley-Liss, Inc.
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  • 67
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    Chirality 5 (1993), S. 422-427 
    ISSN: 0899-0042
    Keywords: 2-arylpropionates ; enantiomers ; stereoselectivity ; chiral inversion ; pharmacokinetics ; bile-duct cannulated rats ; biliary excretion ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: To examine the stereoselectivity of biliary excretion, the optically pure enantiomers of ketoprofen (KT), ibuprofen (IBU), and flurbiprofen (FLU) were intravenously administered to normal and bile duct-cannulated rats at 10 mg/kg. The recovery of total KT in bile was significantly higher after administration of (S)-KT than after (R)-KT [90.1 ± 3.5% vs 68.8 ± 8.2%, n =3, P 〈 0.05]. In normal rats the terminal half-life of (R)-KT was significantly shorter than that of (S)-KT after administration of (R)-KT (2.2 ± 0.6 h vs 14.3 ± 4.9 h, n = 3, P 〈 0.05). The terminal half-life of both enantiomers was significantly shorter in rats with continuous bile drainage as compared to normal rats. No significant differences in pharmacokinetic parameters could be found between both enantiomers in bile duct-cannulated animals. The total amount of IBU in bile was slightly higher after administration of (S)-IBU than after (R)-IBU administration. The percentage of (R)-IBU after (R)-IBU administration, however, was very low [(R)-IBU: 1.5 ± 0.9%, (S)-IBU: 23.4 ± 5.8%]. In normal rats the clearance of (R)-IBU was significantly higher as compared to (S)-IBU. Differences in pharmacokinetic parameters between normal and bile duct-cannulated rats were not statistically significant due to high interindividual variability. The total recovery of FLU, which was excreted in bile to a lower extent than either KT or IBU, also tended to be greater after S-enantiomer administration. Only small amounts of (S)-FLU could be recovered in bile after (R)-FLU administration. The pharmacokinetic parameters did not differ significantly between (R)- and (S)-FLU or between normal and bile duct-cannulated rats due to its low inversion rate and low excretion via bile. © 1993 Wiley-Liss, Inc.
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  • 68
    ISSN: 0899-0042
    Keywords: verapamil ; dissolution ; stereospecific ; enantiomer ; HPLC ; in vitro ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The determination of the in vitro dissolution profiles of three different modified-release formulations of (±)-verapamil were determined and compared to a reference (Calan SR). The determination of (±)-verapamil utilized a microwave-facilitated derivatization reaction with an enantiomerically pure reagent followed by measurement of drug by reversed-phase high-performance liquid chromatography (HPLC). The dissolution profile of each of the four modified-release formulations was followed for the first hour in simulated gastric fluid (pH 1.2) and then in simulated intestinal fluid (pH 7.5) for up to a total of 12 h. The resulting dissolution profiles of each modified-release formulation suggested that only one of the three test formulations had a similar dissolution to the Calan SR reference. Interestingly, the (S:R)-enantiomer ratios of two of the test products were significantly different from unity, and the third test product was also significantly different from unity if 4 out of 5 outliers were omitted. It is suggested that dissolution testing of modified-release formulations containing chiral active ingredients must be stereospecific in order to discern whether a drug-excipient interaction occurs. Additionally, it may be suggested that dissolution techniques relying more upon diffusion of medium through the tablet matrix, rather than erosion of the tablet, may accentuate enantiomeric differences in release rates. © 1993 Wiley-Liss, Inc.
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  • 69
    ISSN: 0899-0042
    Keywords: asymmetric induction ; circular dichroism ; Cotton effect ; dialdo carbohydrate derivative ; diastereo-selectivity ; diastereozero-plane ; ellipticity exaltation ; IR spectroscopy ; magnesium enediolate ; relative configuration ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: To control stereoselectivity in aldol-like reactions with chiral carbohydrate templates, we studied the interaction between completely protected dialdo compounds and magnesium enediolates of arylacetic acids. Diastereomeric mixtures of the highly functionalized acids obtained were esterified to isolate individual methyl uronates. It was found that all the diastereomeric esters exhibit Cotton effects of the same positive sign in the 220-230 nm region and so possess the same S configuration of the aryl chiral center C(6). Chiral center C(5) configurational assignments were performed using IR and ORD spectroscopy. We separated and specified four pairs of diastereomeric methyl uronates. It follows that the precursory acids have the same 5R*, 6S (major isomers) and 5S*, 6S (minor isomers) configurations. A tentative mechanism for complexation and possible models of Mg2+ -protected dialdose intermediate complexes has been proposed. We have concluded that a kind of orbital steering is realized, accompanied by some “tuning” of molecular assembly conditioned by two-point coordination between Mg2+ and potential cation-binding sites in the substrate molecules. Thus it has been demonstrated that reasonable diastereo-selectivity can be achieved even through the use of small matrix molecules using rather small functional groups, which do not impose any stringent steric requirements. © 1993 Wiley-Liss, Inc.
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  • 70
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    Chirality 5 (1993) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 71
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    Chirality 5 (1993), S. 501-504 
    ISSN: 0899-0042
    Keywords: glycidyl 1-naphthyl ether enantiomers ; glycidyl 4-nitrophenyl ether enantiomers ; glutathione conjugation ; epoxide hydrolase ; diol formation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The detoxication of the enantiomers of glycidyl 4-nitrophenyl ether (GNPE), (-)-(R)- and (+)-(S)-GNPE, and glycidyl 1-naphthyl ether (GNE), (-)-(R)- and (+)-(S)-GNE, by rat liver glutathione transferase and epoxide hydrolase was studied. Enantioselectivity was observed with both enzymes favoring the (R)-isomers as determined by the formation of conjugate, diol, and remaining substrate measured by HPLC. Enantiomers of GNE were detoxified by cytosolic epoxide hydrolase but those of GNPE were not. Substantial nonenzymatically formed conjugates of enantiomers of GNPE were detected showing (S)-GNPE the more reactive of the pair. © 1993 Wiley-Liss, Inc.
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  • 72
    ISSN: 0899-0042
    Keywords: enantioselective retention ; albumin ; bilangmuir adsorption model ; frontal analysis ; saturation capacity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: On a column with bovine serum albumin (BSA) immobilized covalently to silica, the adsorption isotherms of the enantiomers of mandelic acid, tryptophan, 2-phenylbutyric acid, and N-benzoylalanine are measured using a buffered mobile phase. Knowing the amount of BSA immobilized on the column (36 mg), the ratio of the number of enantiomer molecules needed to saturate the enantioselective retention mechanism to the number of BSA molecules is determined. The mean of the set of eight enantiomers is 0.28. These data confirm that at most one enantioselective site exists for each BSA molecule for the kind of enantiomers studied. © 1993 Wiley-Liss, Inc.
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  • 73
    ISSN: 0899-0042
    Keywords: chiral discrimination ; chiral stationary phase ; alkyl aryl sulfoxides ; quantitative structure-enantioselective retention relationships ; comparative molecular field analysis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The interaction mechanism of a variety of racemic alkyl aryl sulfoxides with a π-acid HPLC stationary phase containing N,N′-(3,5-dinitrobenzoyl)-trans-1,2-diaminocyclohexane chiral selector was investigated by means of quantum-chemical calculations (MNDO), partial least squares (PLS) analysis, and 3D comparative molecular field analysis (CoMFA). Quantitative structure-enantioselective retention relationships (QSERR), were derived which have yielded significant insights into physicochemical properties primarily responsible for chiral recognition. The increase in retention (k′) is favored especially by the analyte π-basic character, accounted for by the sum of the electrophilic superdelocalizabilities of all aromatic carbon atoms (SPhHOMO), and to minor extent by the H-bond basicity of the sulfoxide oxygen and the hydrophilicity of solutes. In contrast, the separation factor (α) varied mainly with the steric properties of the substituents and with polar and electrostatic properties of the sulfoxide group. A 3D-QSERR analysis using CoMFA methodology has provided a more complete description of factors responsible for chiral recognition and has proven to be a useful tool to examine differences in noncovalent fields (both the electrostatic and the steric) mostly associated with variations of enantioselectivity. © 1993 Wiley-Liss, Inc.
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  • 74
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    Chirality 5 (1993), S. 554-559 
    ISSN: 0899-0042
    Keywords: HPLC ; chiral stationary phases ; resolution of enantiomers ; β-adrenergic blockers ; alcohols ; acetates ; Chiralcel OB ; Chiralcel OD ; Chiralpak OT(+) ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantiomeric purities of optically active intermediates for β-adrenergic blocking agents prepared via enzyme-assisted processes can be determined rapidly and with high accuracy using HPLC on commercially available columns with chiral supports [Chiralcel OD, OB; Chiralpak OT(+)]. The dependence of the resolution parameters on the substitution pattern of both hydroxy compounds and their esters is reported. © 1993 Wiley-Liss, Inc.
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  • 75
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    Chirality 5 (1993), S. 359-365 
    ISSN: 0899-0042
    Keywords: synthetic siderophore analogs ; hydroxamates ; ferrichrome ; ferrioxamine ; coprogen ; Pseudomonas putida ; membrane receptors ; transport proteins ; growth promotion ; growth inhibition ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Molecular recognition by microbial receptors for siderophores [natural iron(III) carriers] is examined with synthetic iron(III) carriers as structural probes. The iron(III) carriers have been designed to reproduce the two essential features of the natural siderophores: the capability to form octahedral iron(III) binding cavities and to fit specific membrane receptors. Specifically, analogs of tripodal ferrichrome and linear ferrioxamines have been prepared and examined. The ferrichrome analogs rely on C3-symmetric binders that are assembled from triscarboxylates as anchors, amino acids as bridges, and terminal hydroxamate groups as binding sites. The ferrioxamine analogs are based on linear assemblies of three identical monomers, each derived from a chiral amino acid. The deliberate use of animo acid residues as variable building blocks enables us to systematically modify the molecules' envelopes and the preferred absolute configuration of the iron(III) complexes until optimal performance is reached. Examination of the synthetic analogs in Pseudomonas putida demonstrates that the domains around the iron(III) center and their chiral sense dictate the extent of recognition by the membrane receptors. It is also shown that the synthetic siderophore analogs may be designed to either exert a broader, or a more narrow range of microbial activity than the natural siderophores. The implications of these findings are discussed in relation to the possible design of species-specific antimicrobial agents. © 1993 Wiley-Liss, Inc.
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  • 76
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    Chirality 5 (1993), S. 379-384 
    ISSN: 0899-0042
    Keywords: biosynthesis ; multidimensional gas chromatography ; peach-like aroma ; enantiomeric ratio ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A filamentous fungus, Fusarium poae INRA 45, was grown in two liquid Czapek-type media (a Czapek medium, and a yeast extract plus casaminoacids-enriched Czapek medium). Eight γ-lactones, i.e., γ-penta-, γ-octa-, γ-nona-, γ-deca-, and γ-dodecalactone, (6Z)-γ- and (6E)-γ-dodecenolactones, and a di-unsaturated γ-dodecalactone, were tentatively, or conclusively, identified by capillary gas chromatography (GC) and coupled GC-MS, in the volatile fractions of the cultures. Kinetics of the formation of γ-decalactone, (6Z)-γ- and (6E)-γ-dodecenolactones, (three major lactones), and γ-dodecalactone (a minor lactone) were quantitatively studied by computerized GC integration. Variations of the (R/S) ratios of the lactone enantiomers were quantitatively studied by computerized multidimensional gas chromatography (MDGC) integration. The levels of the lactones were superior in the enriched Czapek-type medium to those of the Czapek medium, but the compositions of these media did not influence significantly the (R/S) ratios of these lactones. Formation of the enantiomers is discussed in terms of metabolism of potential precursors. © 1993 Wiley-Liss, Inc.
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  • 77
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    Chirality 5 (1993), S. 405-406 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 1 Ill.
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  • 78
    ISSN: 0899-0042
    Keywords: atenolol enantiomers ; enantioselective HPLC bioassay ; stereoselective pharmacokinetics ; oxazolidine-2-one derivative ; fluorimetric detection ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An enantioselective HPLC bioassay has been developed relying on extraction of (R)- and (S)-atenolol from alkalinized plasma or serum (pH 〉 12) into dichloromethane containing 5% (v/v) 1-butanol followed by an achiral derivatization of the drug with phosgene leading to (R)- and (S)-oxazolidine-2-one derivatives. Under these conditions there was quantitative conversion of the acetamido group to the corresponding nitrile. These stable derivatives were separated on a (R,R)-diaminocylohexane-dinitrobenzoyl chiral stationary phase [(R,R)-DACH-DNB] using dichloromethane/methanol 98/2 as mobile phase. Determination limits of 0.5 ng for (R)- and 0.6 ng for (S)-atenolol could be achieved using fluorimetric detection. The assay was applied to a human pharmacokinetic study which was performed in a randomized cross-over, double-blind fashion in 12 healthy volunteers, administering single oral doses of 100 mg (R,S)-, 50 mg (R)-, and 50 mg (S)-atenolol AUC0-24 and Cmax values of (R)-atenolol were slightly but significant higher than those of (S)-atenolol. The R/S ratios were 1.09 for AUC(R)/AUC(S) and 1.03 for Cmax (R)/Cmax(S) (P 〈 0.01) respectively after administration of the racemic drug. However, there were no differences between AUC, Cmax, and t½ values of each enantiomer, whether they were administered as single enantiometers or in the form of its racemic mixture. © 1993 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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  • 79
    ISSN: 0899-0042
    Keywords: cellulose ; amylose ; silica gel ; high performance liquid chromatography ; direct separations ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Direct enantiomeric separations of 17 chiral amidotetralins by means of high performance liquid chromatography were performed on stationary phases composed of tris(3,5-dimethylphenylcarbamate) derivatives of cellulose and amylose, coated on silica gel. The enantiomers of 15 out of 17 amidotetralins were resolved with a resolution of more than 1.5 by at least one of the chiral stationary phases. The stationary phases showed complementary results with regard to the separation of the amidotetralins, that is, pairs that did not separate on the cellulose-type column were well separated on the amylose-type column, and vice versa. There was no significant correlation between the chromatographic properties of the chiral stationary phases. © 1993 Wiley-Liss, Inc.
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  • 80
    ISSN: 0899-0042
    Keywords: chiral additive ; cyclodextrin ; RP-HPLC ; atropisomers ; experimental design ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The effect of the position and type of the substituent on the chromatographic separation of N-arylthiazoline-2-thione and arylthiazoline-2-one atropisomers are described in reversed-phase HPLC using β- or -β-cyclodextrin as chiral mobile phase additive. A quantitative approach to experimental design has been developed. © 1993 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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  • 81
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    Chirality 5 (1993), S. 483-483 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 82
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    Chirality 5 (1993), S. 492-494 
    ISSN: 0899-0042
    Keywords: GI-side effects ; NSAID ; ulcerogenicity ; rac-flurbiprofen enantiomers ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The most common, and sometimes life-threatening, side-effects associated with the human use of the analgesic, nonsteroidal antiinflammatory drugs (NSAIDs) are gastrointestinal. These include gastritis, ulceration, and severe bleeding. The aryl propionic acid class of NSAIDs are among the most widely used of these drugs in the world, including rac-ibuprofen, rac-flurbiprofen, and rac-ketoprofen. Marketed as racemates, it was assumed that the “inactive” (R)-enantiomers, having no cyclooxygenase inhibiting effect, also had no toxic effect. In a 30-day dose response study of (S)-, (R)-, and rac-flurbiprofen given daily over a range of doses the (R)-isomer alone proved to be without apparent gastrointestinal (GI) toxicity. On the other hand the racemate proved to be 2 to 4 times as ulcerogenic in enantiomerically equivalent doses as the (S)-enantiomer. These results have significant clinical implications. © 1993 Wiley-Liss, Inc.
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  • 83
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    Chirality 5 (1993), S. 485-491 
    ISSN: 0899-0042
    Keywords: anaesthetics ; local:bupivacaine ; enantiomers:stereoselective pharmacokinetics ; enantiomers:stereoselective pharmacodynamics ; enantiomers:tissue distribution ; sheep ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: rac-Bupivacaine HCl was infused intravenously to constant arterial blood drug concentrations in sheep using a regimen of 4 mg/min for 15 min followed by 1 mg/min to 24 h. At 24 h, arterial blood was sampled, the animal was killed with a bolus of KCl solution, then rapidly dissected and samples were obtained from heart, brain, lung, kidney, liver, muscle, fat, gut, and rumen. Tissue:blood distribution coefficients for (+)-(R)-bupivacaine exceeded those of (-)-(S)-bupivacaine (P 〈 0.05) for heart, brain, lung, fat, gut, and rumen by an overall mean of 43%. Blood:plasma distribution coefficients of (-)-(S)-bupivacaine exceeded those of (+)-(R)-bupivacaine by a mean of 29% and this offset the tissue:blood distribution coefficients so that the previously significant enantioselective differences disappeared. It is concluded that although enantioselectivity of bupivacame distribution is shown by the measured tissue:blood distribution coefficients, it is not shown when tissue:plasma water distribution coefficients are calculated, suggesting that there is no intrinsic difference between the bupivacaine enantiomers in tissue affinity. Sheep given fatal intravenous bolus doses of rac-bupivacaine had significantly greater concentrations of (+)-(R)-bupivacaine than (-)-(S)-bupivacaine in brain (P = 0.028) and ventricle (P = 0.036); these could augment the greater myocardial toxicity of this enantiomer found in vitro. © 1993 Wiley-Liss, Inc.
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  • 84
    ISSN: 0899-0042
    Keywords: CTA I ; chiral recognition ; enthalpy of complexation ; titration ; interaction sites ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The resolution of racemic δ-phenyl-δ-valerolactone by chromatography on cellulose triacetate CTA I results in one of the best separations of optical antipodes observed so far on this chiral stationary phase. The thermodynamics of the stereoselective interaction of the enantiomers of δ-phenly-δ-valerolactone have been studied by chromatography at different temperatures and by direct microcalorimetric investigations of the complexation with CTA I. This analysis suggests that the separation process is mainly controlled thermodynamically and that kinetic effects, if any, play a minor role. Microcalorimetric titration experiments indicate that specific (optimum) complexation sites on CTA I for the stronger retained enantiomer of δ-phenly-δ-valerolactone are rapidly saturated, whereas the first eluted enantiomer seems to interact much less selectively with defined interaction sites on the chiral polymer matrix. © 1993 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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  • 85
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The Gibbs energies of activation of the solvolytic reactions of tert-butyl halides (chloride, bromide and iodide) in eight mono-alcohols and eight di-alcohols were dissected into contributions from the initial state and transition state. The unified approach proposed by Abraham was applied and the various factors making up the overall solvent effect in both states were identified and compared. To perform this study, the Gibbs energies of transfer of the initial state were calculated using the infinite dilution activity coefficient values of the solutes in the solvents, γ∞. These values were determined from the UNIFAC group-contribution method, with the modified Flory-Huggins equation in the combinatorial term and with group interaction parameters from the Parameter Table exclusively based on experimental γ∞ data reported in the literature. It is concluded that solvent polarizability and polarity-HBD acidity and cavity effects during the activated process are mainly due to transition-state contributions.
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  • 86
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    Journal of Physical Organic Chemistry 6 (1993), S. 163-170 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The molecular structure of [4] metacyclophane is optimized at the ab initio STO-3G SCF level and a genuine minimum is located. In the STO-3G structure the benzene ring is less bent and geometrically distorted than in the previously reported MNDO structure. Although some bond alternation is calculated for the carbon-carbon bond lengths of the bent benzene ring, their values still fall in the range of highly delocalized compounds. Despite the fact that the STO-3G strain energy [SE(tot.)] is larger than the corresponding MNDO strain energy, the distribution of SE(tot.) over the bent benzene ring [SE(bb.)] and the oligomethylene bridge [SE(br.)] is similar. To facilitate the hitherto unsuccesful identification of [4] metacyclophane, its electronic transition energies were calculated with CNDO/S-CI using the STO-3G geometry as input geometry. The reliability of the CNDO/S-CI results was assessed by a comparison of calculated and experimental electronic transition energies for p- and, m-xylene, [5] para- and [5] metacyclophane and [4] paracyclophane following the same approach.
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  • 87
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The stoichiometry of the reaction of TIIII with ascorbic acid (H2A) in the presence and absence of chloride ion conforms to TIIII + H2A 〉 TII + 2H+ + A. where A is dehydroascorbic acid. The reaction exhibits complex kinetics and the reactivity of various chlorothallium (III) species decreases in the order of [TIOH]2+ 〉 TI3+ 〉 [TICI]2+ 〉 [TICI2]+ 〉 TICI3 〉 [TICI4]-. The mass balance relationship was employed to calculate the equilibrium concentration of the chloride ion for evaluation of the rate constants.
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  • 88
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    Journal of Physical Organic Chemistry 6 (1993), S. 193-194 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
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  • 89
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Substituent effects on the thermal elimination reactions of carbonates and thiocarbonates were investigated MO theoretically using the AM1 method. For both substrates, an electron-withdrawing group is found to facilitate the decomposition. A two-step process is favoured by carbonates, whereas one- and two-step processes can compete in the pyrolysis of thiocarbonates. The ability to transmit substituent effect is greater with oxygen (carbonates) than with sulphur (thicarbonates) in contrast to the experimental results of Taylor and co-workers. Modelling studies with replacement of the phenyl ring with a vinyl group are found to be justified in this type of work.
    Additional Material: 9 Tab.
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  • 90
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The erythro-thioimidazole precursor to the cyclopropyloxiranylmethyl radical has been prepared. Treatment with 7-19 equiv. of triphenyltin hydride at 70°C gave only 3-cyclopropylprop-2-en-1-ol, the product of epoxide ring opening. No product in which the cyclopropyl ring had opened was observed. Kinetic analysis allowed the assignment of a lower limit for the rate of oxiranylcarbinyl radical rearrangements of 1 × 1010 s-1 at this temperature.
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  • 91
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    Journal of Physical Organic Chemistry 6 (1993), S. 251-253 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The calorimetric isotherm of water sorption by solid human serum albumin (HSA) was measured in water-dioxane mixtures. This isotherm has been successfully described at low water contents in the solvent within the framework of the presented model. The adsorption equilibrium constant and the monolayer formation energy were estimated from this model. The interaction enthalpies of solid HSA with the solvent in water-rich mixtures do not differ essentially from the solution enthalpy of HSA in water. This means that the solvent water content may be sufficient for the intermolecular interactions of HSA suspended in a water-organic mixture to be similar to those in aqueous protein solution.
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  • 92
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The crystal and molecular structure of N-nitro-N-methyl-p-nitroaniline was solved with good precision: R = 0·058 and average estimated standard deviation for bond lengths = 0·003 Å. Analysis of the geometry reveals that the NO2 attached to the N atom is strongly conjugated. Application of the HOSE model to its geometry and to geometries of 12 other para-substituted nitrobenzenes yields good linear regressions between canonical structure weights and Hammett σ values by interpolation, σ for the N(Me)NO2 group is estimated to 0·36.
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  • 93
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    Journal of Physical Organic Chemistry 6 (1993), S. 281-286 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The Marcus cross relation provides a tool to calculate cross rates from the corresponding identity rates and the equilibrium constant. Assumptions made in deriving the Marcus cross relation and conclusions which can be drawn from agreement or disagreement between experimental and calculated cross rates are discussed. For a small variation in identity rate constants, agreement between experimental and calculated cross rates are discussed. For a small variation in identity rate constants, agreement between experimental and calculated cross rates simply means that the rate constant of a hypothetical thermoneutral cross reaction has a value within the range covered by the identity rates. Whether or not this value corresponds to the mean value of logarithmic identity rate constants can only be checked for a large variation in identity rates. Therefore, a newly defined index M is used to relate the difference in experimental and calculated logarithmic rate constants to the variation in the logarithmic identity rates. Provided that the Marcus cross relation is not obeyed, this indicates non-additivity of kinetic parameters. Applying this analysis to protontransfer reactions between different transition metal acids and between 9-alkylflourenes and (9-alkylfluorenyl)lithium shows that claims about agreement or disagreement of experimental rate constants with the rate constants calculated by means of the Marcus cross relation have to be revised in part.
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  • 94
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    Journal of Physical Organic Chemistry 6 (1993), S. 302-306 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: A thermodynamic hydrogen-bond basicity scale, pKHB, and a spectroscopic hydrogen-bond basicity scale, Δν(OH), were measured which permitted the construction of the solute hydrogen-bond basicity scale, β2H, for 71 nitriles embracing a wide range of structures from trichloroacetonitrile to cyanamides. Field, resonance, and polarizability contributions of the X substituents to the hydrogen-bond basicity of XCN compounds were established. Steric effects do not contribute to the hydrogen-bond basicity of nitriles.
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  • 95
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    Journal of Physical Organic Chemistry 6 (1993) 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
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  • 96
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    Journal of Physical Organic Chemistry 6 (1993), S. 341-346 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The UV spectra of 3,4-diphenyl-1,2,5-thiadiazole 1,1-dioxide (I) and that of its thiadiazoline and thiadiazolidine derivatives were measured in several aprotic and protic solvents. Strong specific interactions of I with protic solvents are observed and the formation of stable carbinolamine type derivatives of I with methanol or ethanol is proposed. Spectroscopic data (UV, 1H and 13C NMR) and electrochemical evidence for their formation are given and a new thiadiazoline derivative of I (3-ethoxy-2-methyl-3,4-diphenyl-1,2,5-thiadiazoline 1,1-dioxide) was synthesized. The equilibrium constant for the reaction of I with ethanol is reported.
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  • 97
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    Journal of Physical Organic Chemistry 6 (1993), S. 361-366 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The negative slope (ΔρY+ 〈 0) of the Hammett-type plot using kinetic solvent isotope effect, log kSOH/kSOD versus σ+, for methanolysis of 1-(Y-phenyl)ethyl chlorides is rationalized by an ion-pair mechanism in which a solvent molecule attacks the relatively stable carbocation formed in the pre-equilibrium.
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  • 98
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    Journal of Physical Organic Chemistry 6 (1993), S. 357-360 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The nucleophilic substitution reactions of isopropyl arenesulphonates with anilines and benzylamines in acetonitrile at 65·0°C were investigated. The cross-interaction constants ρxz (and βxz) between substituents in the nucleophile (X) and leaving group (Z) are positive and relatively small. The transition state (TS) variation is consistent with that predicted by the More O'Ferrall-Jencks diagram, as expected from the positive ρxz. The small magnitude of ρxz correctly reflects a relatively loose TS structure, in contrast to the tight TS for ethyl (or methyl) derivatives under similar reaction conditions.
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  • 99
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    Journal of Physical Organic Chemistry 6 (1993) 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
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  • 100
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    Journal of Physical Organic Chemistry 6 (1993), S. 376-379 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The 1,2-carbenic hydride shift of neopentylmethoxycarbene was suppressed by the methoxy substituent. Thermally activated hydride shifts were observed with phenoxymethylmethoxycarbene and phenoxymethyltrifluoro-ethoxycarbene, where appropriate potentiating substituents were introduced at both the migration origin and the migration terminus. Similarly, the 1,3-CH insertion reaction of tert-butylfluorocarbene could be induced by thermal activation.
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