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Enantiomeric Purity (enantiomeric + purity)
Kinds of Enantiomeric Purity Selected AbstractsAn Asymmetric Catalytic Darzens Reaction between Diazoacetamides and Aldehydes Generates cis -Glycidic Amides with High Enantiomeric Purity,ANGEWANDTE CHEMIE, Issue 35 2009Wei-Jun Liu Dr. Titanverstärkt: Die Titelreaktion wurde durch einen chiralen Titankomplex katalysiert, der in,situ aus käuflichem Ti(OiPr)4 und (R)-Binol gebildet wurde, und lieferte mit ausgezeichneter Enantiomerenreinheit cis -Glycidamide (siehe Schema). Mit dieser neuen Methode wurden chirale Bausteine für die Synthese der Seitenketten von Taxol und (,)-Bestatin hergestellt. [source] ChemInform Abstract: Efficient Syntheses of Fluorinated Aryl Alcohols of High Enantiomeric Purity via Boronic Esters.CHEMINFORM, Issue 12 2001Rajendra P. Singh Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Enantiomeric purity of (+/,)-methyl jasmonate in fresh leaf samples and commercial fragrancesJOURNAL OF SEPARATION SCIENCE, JSS, Issue 13 2007Maria L. Ruiz del Castillo Abstract The enantiomeric purity of (+/,)-methyl jasmonate in fresh leaf material of Jasminum from different species and Rosmarinus officinalis was examined by solid-phase microextraction-GC-MS (SPME-GC-MS). For comparison with these natural products, commercial jasmine and rosemary fragrances were also studied. The extraction conditions were selected as a result of testing different values of temperature (40, 50, and 60°C) and time (2, 15, 30, and 40 min). The results obtained in this work revealed a range of enantiomeric excesses for (+/,)-methyl jasmonate varying from 13 to 95% depending on the Jasminum specie considered. In contrast, (,)-methyl jasmonate always occurred as a pure enantiomer in all R. officinalis samples studied. This implies those Jasminum species in which the enantiomeric purity of (,)-methyl jasmonate is high enough and any R. officinalis sample might be used as natural sources of pure (,)-methyl jasmonate. Concerning the commercial fragrances, those of jasmine showed enantiomeric composition of (,)-methyl jasmonate ranging from 1 to 15% whereas those of rosemary exhibited practically the pure (,)-methyl jasmonate. This fact suggests the addition and nonaddition of the racemic mixture of methyl jasmonate to the commercial jasmine and rosemary samples, respectively. [source] Semipreparative chiral supercritical fluid chromatography in the fractionation of lansoprazole and two related antiulcer drugs enantiomersJOURNAL OF SEPARATION SCIENCE, JSS, Issue 8 2008Laura Toribio Abstract The semipreparative chiral separation of lansoprazole and two related compounds (pantoprazole and rabeprazole) using supercritical fluid chromatography (SFC) is presented in this work. Different loads were evaluated in order to obtain high enantiomeric purities and production rates. The volumes injected were 1, 2 and 4 mL. The concentrations of the racemic mixtures were 3 and 6 g/L for lansoprazole and 1.5 g/L for pantoprazole and rabeprazole. In all the cases, the recoveries, for a purity higher than 99.9%, were better for the second eluted enantiomer than for the first one. This fact conditioned the production rate of the first eluted enantiomer that, considering a fixed purity, was always lower than that obtained for the other one. In the case of lansoprazole it was possible to obtain 0.025 and 0.090 mg/min of the first and second eluted enantiomer, respectively, with an enantiomeric purity of 99.9%. For rabeprazole enantiomers 0.037 and 0.062 mg/min, and in the case of pantoprazole the results were better (0.062 and 0.122 mg/min) due to the higher resolution. [source] Enantiomeric composition studies in Lavandula species using supercritical fluidsJOURNAL OF SEPARATION SCIENCE, JSS, Issue 17 2005Gema Flores Abstract Characteristic aroma compounds in plants and essential oils of Lavandula from different varieties were examined. The study of the qualitative and quantitative composition of the major volatile components was faced by developing a method based on the use of supercritical fluid extraction-GC-MS (SFE-GC-MS). The optimization of a variety of parameters affecting SFE extraction enabled RSDs from three replicates lower than 2% to be achieved. Equally, recoveries of up to 59% were obtained by applying the proposed method. The use of multidimensional GC was necessary to enantiomerically resolve the target compounds. The obtained results showed enantiomeric purities >90% for all studied compounds in all varieties considered, proving the natural invariability of the enantiomeric composition of the compounds of interest. This information can be useful in authenticity studies as well as in selecting natural sources of enantiomerically pure compounds. [source] Chiral NMR discrimination of amines: Analysis of secondary, tertiary, and prochiral amines using (18-crown-6)-2,3,11,12-tetracarboxylic acid,CHIRALITY, Issue 3-4 2008Ann E. Lovely Abstract Enantiomeric discrimination is observed in the 1H and 13C NMR spectra of secondary and tertiary amines in the presence of (,)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (1). Nonequivalence of the resonances of prochiral nuclei in primary and secondary amines is also observed when they associate with 1. The amines are added in their neutral form and are protonated by the carboxylic acid groups of 1 to produce the corresponding ammonium and carboxylate ions. Secondary amines associate with 1 through two hydrogen bonds and an ion pair interaction. Tertiary amines can only form one hydrogen bond to accompany the ion pairing. Chiral discrimination in the 1H and 13C NMR spectra of a series of aryl-containing secondary amines is of sufficient magnitude to determine enantiomeric purities. The discrimination in the spectra of tertiary amines with 1 is smaller, but 13C NMR spectra provided enough distinction for the determination of enantiomeric purity. Chirality, 2008. © 2007 Wiley-Liss, Inc. [source] Advances in the enantioseparation of second-generation antidepressant drugs by electrodriven methodsELECTROPHORESIS, Issue 1 2006Roberto Mandrioli Abstract Stereochemistry is steadily increasing in importance in the development of new drugs, and the availability of pure enantiomer drugs can make therapy safer and more efficacious. In particular, almost all second-generation antidepressant drugs possess one or more chiral centres; however, only some of them are administered as single enantiomers. A fundamental part of the quality control of pharmaceutical formulations is the determination of enantiomeric excess and enantiomeric purity; this is also important for the therapeutic drug monitoring of depressed patients. For this purpose, efficient and reliable analytical methods are needed and electrodriven techniques (most of all CE, CEC and MEKC) are very efficient and inexpensive candidates for the role. In this review, the enantioselective electrodriven methods available for the analysis of second-generation antidepressant are presented and discussed. In particular, the following pharmacological classes of antidepressants will be considered: selective serotonin reuptake inhibitors (fluoxetine, citalopram, paroxetine, sertraline); norepinephrine reuptake inhibitors (reboxetine); serotonin and norepinephrine reuptake inhibitors (venlafaxine, milnacipran, duloxetine); and noradrenergic and specific serotonergic antidepressants (mirtazapine). [source] Determination of enantiomeric purity of a novel COX-2 anti-inflammatory drug by capillary electrophoresis using single and dual cyclodextrin systemsELECTROPHORESIS, Issue 9 2003Carlos Pérez-Maseda Abstract E-6087 is the most advanced compound among the cyclooxygenase-2 (COX-2) inhibitor drugs developed in our company. Its activity is mainly associated with the S(,)-enantiomer (E-6232), whereas the R(,)-enantiomer (E-6231) becomes an impurity whose content should be determined. Five main impurities and degradation products of E-6232 have been found (E-6144, E-6024, E-6072, E-6397 and E-6132), and some of them co-elute with the distomer when using a chiral high-performance liquid chromatography (HPLC) method. Consequently, we have optimized the separation of all the impurities from the two enantiomers of E-6087 by capillary electrophoresis (CE), in order to use the method for the enantiomeric purity determination of E-6232. The effect of the methanol (MeOH) content in the background electrolyte (BGE), the sulfobutyl ether-,-cyclodextrin (SBE-,-CD) and heptakis-(2,6-di- O -methyl)-,-cyclodextrin (DM-,-CD) concentration, and the capillary temperature have been studied. Separation of all compounds could be achieved in different systems, either in a single CD-system (with SBE-,-CD) or in a dual CD-system (with DM-,-CD as a neutral CD). By using the dual CD system a limit of detection (LOD) and a limit of quantitation (LOQ) of 0.03% and 0.1% of distomer, respectively, were achieved*. [source] Chiral alcohol production by NADH-dependent phenylacetaldehyde reductase coupled with in situ regeneration of NADHFEBS JOURNAL, Issue 9 2002Nobuya Itoh Phenylacetaldehyde reductase (PAR) produced by styrene-assimilating Corynebacterium strain ST-10 was used to synthesize chiral alcohols. This enzyme with a broad substrate range reduced various prochiral aromatic ketones and ,-ketoesters to yield optically active secondary alcohols with an enantiomeric purity of more than 98% enantiomeric excess (e.e.). The Escherichia coli recombinant cells which expressed the par gene could efficiently produce important pharmaceutical intermediates; (R)-2-chloro-1-(3-chlorophenyl)ethanol (28 mg·mL,1) from m -chlorophenacyl chloride, ethyl (R)-4-chloro-3-hydroxy butanoate) (28 mg·mL,1) from ethyl 4-chloro-3-oxobutanoate and (S)- N-tert -butoxycarbonyl(Boc)-3-pyrrolidinol from N -Boc-3-pyrrolidinone (51 mg·mL,1), with more than 86% yields. The high yields were due to the fact that PAR could concomitantly reproduce NADH in the presence of 3,7% (v/v) 2-propanol in the reaction mixture. This biocatalytic process provided one of the best asymmetric reductions ever reported. [source] Enantiomeric composition of (E)- and (Z)-sabinene hydrate and their acetates in ,ve Origanum spp.FLAVOUR AND FRAGRANCE JOURNAL, Issue 2 2005Olga Larkov Abstract The enantiomers of (E)- and (Z)-sabinene hydrate and of (E)- and (Z)-sabinene hydrate acetate from extracts of Origanum ramonense Danin, O. dayi Post, O. majorana L., O. vulgare L. ssp. vulgare and O. syriacum L. ssp. syriacum were analysed by GC,MS with chiral and non-chiral capillary columns. The order of elution, the enantiomeric ratios and relative percentages of the four pairs of enantiomers were determined. The (1S)-enantiomers of (E)-sabinene hydrate and (E)-sabinene hydrate acetate were predominant in O. dayi, whereas in the other Origanum spp. the (1R)-enantiomers were predominant. (Z)-sabinene hydrate acetate was not detected in O. syriacum, while the (1R)-enantiomer was present in an optically pure form in O. ramonense, O. majorana and O. vulgare; in O. dayi the enantiomeric purity was 97%. The enantiomeric distributions of (E)- and (Z)-sabinene hydrate and their acetates were determined for the ,rst time in Origanum spp. Copyright © 2004 John Wiley & Sons, Ltd. [source] Catalytic Asymmetric Synthesis of Branched Chiral Allylic Phenyl Ethers from (E)-Allylic AlcoholsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 18 2009Angela Abstract The first di-,-amidate dipalladium complexes and a new di-,-carboxylate dipalladium complex of the COP (cobalt oxazoline palladacycle) palladium(II) catalyst family are reported and characterized crystallographically. The di-,-amidate complex 3 and its enantiomer (ent - 3) are the first asymmetric catalysts that allow commercially available, or readily accessible, (E)-2-alken-1-ols to be transformed to enantioenriched branched allylic aryl ethers upon reaction of their trichloroacetimidate derivatives with phenols. The 3-aryloxy-1-alkene products are formed in high enantiomeric purity (typically 90,98% ee) and useful yields (61,88%). [source] Facile Synthesis of Enantiopure 4-Substituted 2-Hydroxy-4- butyrolactones using a Robust Fusarium LactonaseADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 17 2009Bing Chen Abstract A facile chemo-enzymatic process has been developed for producing stereoisomers of 4-substituted 2-hydroxy-4-butyrolactones with good to excellent enantioselectivity. This process involves an easy separation of the diastereoisomers by column chromatography and efficient enzymatic resolution by whole cells of Escherichia coli JM109 expressing Fusarium proliferatum lactonase gene. This biocatalyst shows strong tolerance towards different substrate structures and at least three out four possible isomers could be obtained in excellent enantiomeric purity. Different substrate concentrations (10,mM,200,mM) were examined, giving a substrate to catalyst ratio of up to 26:1. This general and efficient enzymatic process provides access to stereoisomers of 4-substituted 2-hydroxy-4-butyrolactones readily and cost-effectively. The stereochemical assignments were conducted systematically based on NMR, X-ray diffraction and circular dichroism, leading to further understanding of the enzyme's stereoselectivity. [source] One-Pot, Regioselective Synthesis of Substituted Arylglycines for Kinetic Resolution by Penicillin G AcylaseADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 11-12 2008Peter Grundmann Abstract Amido-alkylation of electron-rich arenes with phenylacetamide and glyoxylic acid offers an inexpensive route to a large variety of N -phenylacetylated arylglycines that are suited for immediate enzymatic resolution by penicillin G acylase. When performed under mild conditions at 5,°C in acetic acid/HCl, this simple one-pot operation resulted in the formation of single regioisomers only (,98%). Subsequent kinetic resolution of the amino acid derivatives by penicillin G acylase at pH,8.0 occurred generally with E values>100 and thus furnished free (S)-configurated arylglycines with high enantiomeric purity. The corresponding enantiopure (R)-substrates, easily separable by a phase-selective extraction process, provided the corresponding (R)-enantiomers upon conventional hydrolysis. This one-pot, two-step procedure for arylglycine synthesis, resolution and work-up requires a minimum of equipment and grants rapid access to both enantiopure (S)- and (R)-antipodes of non-natural ,-amino acids in small- to large-scale quantities. [source] Synthesis and deuterium labelling of the pure selective estrogen receptor modulator (SERM) acolbifene glucuronidesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 3 2007Jean-Yves Sancéau Abstract Acolbifene (EM-652·HCl, SCH 57068·HCl), a highly potent and orally active selective estrogen receptor modulator (SERM), is at late stage clinical development for the treatment of estrogen-sensitive breast cancer. Acolbifene-7-glucuronide 1 (major) and acolbifene-4,-glucuronide 2 (minor) were identified as metabolites of acolbifene in the human. The two monoglucuronides and a diglucuronide 3 as well as the corresponding 2H-labelled derivatives 4,6 were synthesised for use as preclinical and clinical standards for LC,MS/MS analysis. All glucuronides were prepared by the Schmidt glycosylation of monoprotected acolbifene with a glucuronyl imidate at ,10°C to prevent epimerisation at the C-2 position. The two monoglucuronides 1 and 2 of acolbifene were separated by semi-preparative HPLC. Incorporation of three deuteriums was achieved by alkylation of chromanone 15 with C2H3MgI followed by dehydration with C2H3CO22H/2H2O. After chemical resolution and salt neutralisation, [2H3]acolbifene 19 was obtained with 99.4% enantiomeric purity and >98% isotopic purity. Copyright © 2007 John Wiley & Sons, Ltd. [source] Mechanistic studies of intramolecular CH insertion reaction of arylnitrenes: isotope effect, configurational purity and radical clock studiesJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 1 2005Shigeru Murata Abstract In order to reveal the mechanism of the intramolecular CH insertion of arylnitrenes, three experiments were carried out: measurement of isotope effects, determination of the extent of configurational retention and radical clock studies. Irradiation of the deuterium-substituted azide 4 - d in an inert solvent exclusively afforded the indolines 5 - h and 5 - d, in which the kinetic isotope effect kH/kD on the intramolecular CH insertion of the nitrene was evaluated as 12.6,14.7 at room temperature. A chiral chromatographic analysis of the indoline 11 obtained from the optically active azide (S)- 6 revealed that the enantiomeric purity of the starting azide was almost completely lost during the intramolecular CH insertion of the photolytically generated nitrene (enantiomeric excess <10%). The thermolysis of the azide 7 at 180°C mainly gave a mixture of the cyclopropyl ring-opened products 20,22, together with the intramolecular CH insertion product with an intact cyclopropyl ring 19. On the basis of these observations, we concluded that the intramolecular CH insertion of the nitrene proceeds primarily by the hydrogen abstraction,recombination mechanism. We propose, however, a small contribution of the concerted mechanism to the intramolecular CH insertion, based on the solvent dependence of the isotope effect and the extent of the configurational retention. Copyright © 2004 John Wiley & Sons, Ltd. [source] Enantioselective separation of chiral vicinal diols in capillary electrophoresis using a mono-6A -aminoethylamino-,-cyclodextrin as a chiral selectorJOURNAL OF SEPARATION SCIENCE, JSS, Issue 1 2009Peng Liu Abstract This paper describes an improved access to mono-6A -aminoethylamino-,-CD (,-CDen), a very efficient cationic chiral selector for CZE in the separation of eight chiral aromatic vicinal diols. The ,-CDen concentration has a strong influence on the efficiency of enantioseparation. The effects of the pH and concentration of the BGE, the capillary temperature, and the applied voltage on the resolution and separation selectivity have been studied. Excellent chiral resolution was achieved under the optimal conditions of ,-CDen 10 mM, pH 10, 200 mM borate buffer at 15 kV and 20°C within 20 min. Moreover, the developed method was successfully applied to the determination of the enantiomeric purity of the catalytic asymmetric dihydroxylation (AD) reaction products. [source] Semipreparative chiral supercritical fluid chromatography in the fractionation of lansoprazole and two related antiulcer drugs enantiomersJOURNAL OF SEPARATION SCIENCE, JSS, Issue 8 2008Laura Toribio Abstract The semipreparative chiral separation of lansoprazole and two related compounds (pantoprazole and rabeprazole) using supercritical fluid chromatography (SFC) is presented in this work. Different loads were evaluated in order to obtain high enantiomeric purities and production rates. The volumes injected were 1, 2 and 4 mL. The concentrations of the racemic mixtures were 3 and 6 g/L for lansoprazole and 1.5 g/L for pantoprazole and rabeprazole. In all the cases, the recoveries, for a purity higher than 99.9%, were better for the second eluted enantiomer than for the first one. This fact conditioned the production rate of the first eluted enantiomer that, considering a fixed purity, was always lower than that obtained for the other one. In the case of lansoprazole it was possible to obtain 0.025 and 0.090 mg/min of the first and second eluted enantiomer, respectively, with an enantiomeric purity of 99.9%. For rabeprazole enantiomers 0.037 and 0.062 mg/min, and in the case of pantoprazole the results were better (0.062 and 0.122 mg/min) due to the higher resolution. [source] Enantioselective HPLC resolution of synthetic intermediates of armodafinil and related substancesJOURNAL OF SEPARATION SCIENCE, JSS, Issue 6-7 2008Ramisetti Nageswara Rao Abstract Armodafinil is a unique psychostimulant recently approved by the US Food and Drug Administration for the treatment of narcolepsy. The chromatographic resolution of its chiral intermediates including related substances in the total synthesis of armodafinil was studied on polysaccharide-based stationary phases, viz. cellulose tris-(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and amylose tris-(3,5-dimethylphenylcarbamate) (Chiralpak AD-H) by HPLC. The effects of 1-propanol, 2-propanol, ethanol, and trifluoroacetic acid added to the mobile phase and of column temperature on resolution were studied. A good separation was achieved on cellulose-based Chiralcel OD-H column compared to amylose-based Chiralpak AD-H. The effects of structural features of the solutes and solvents on discrimination between the enantiomers were examined. Baseline separation with Rs >1.38 was obtained using a mobile phase containing n -hexane,ethanol,TFA (75:25:0.15 v/v/v). Detection was carried out at 225 nm with photodiode array detector while identification of enantiomers was accomplished by a polarimetric detector connected in series. The method was found to be suitable not only for process development of armodafinil but also for determination of the enantiomeric purity of bulk drugs and pharmaceuticals. [source] Enantiomeric purity of (+/,)-methyl jasmonate in fresh leaf samples and commercial fragrancesJOURNAL OF SEPARATION SCIENCE, JSS, Issue 13 2007Maria L. Ruiz del Castillo Abstract The enantiomeric purity of (+/,)-methyl jasmonate in fresh leaf material of Jasminum from different species and Rosmarinus officinalis was examined by solid-phase microextraction-GC-MS (SPME-GC-MS). For comparison with these natural products, commercial jasmine and rosemary fragrances were also studied. The extraction conditions were selected as a result of testing different values of temperature (40, 50, and 60°C) and time (2, 15, 30, and 40 min). The results obtained in this work revealed a range of enantiomeric excesses for (+/,)-methyl jasmonate varying from 13 to 95% depending on the Jasminum specie considered. In contrast, (,)-methyl jasmonate always occurred as a pure enantiomer in all R. officinalis samples studied. This implies those Jasminum species in which the enantiomeric purity of (,)-methyl jasmonate is high enough and any R. officinalis sample might be used as natural sources of pure (,)-methyl jasmonate. Concerning the commercial fragrances, those of jasmine showed enantiomeric composition of (,)-methyl jasmonate ranging from 1 to 15% whereas those of rosemary exhibited practically the pure (,)-methyl jasmonate. This fact suggests the addition and nonaddition of the racemic mixture of methyl jasmonate to the commercial jasmine and rosemary samples, respectively. [source] Method for enantiomeric purity of a quinuclidine candidate drug by capillary electrophoresisJOURNAL OF SEPARATION SCIENCE, JSS, Issue 13 2006Tore Ramstad Abstract A chiral procedure based on EKC was developed and validated for determination of the enantiomeric purity of PHA-543613, a drug candidate that was under development for treatment of the cognitive deficits of Alzheimer's disease and schizophrenia. Separation of enantiomers is accomplished via differential, enantiospecific complexation with a single-isomer, precisely sulfated beta-CD and heptakis-6-sulfato-,-CD (HpS-,-CD). Both neutral and sulfated CDs were screened before selecting HpS-,-CD as the chiral selector. The separation is conducted in a 61 cm×50 ,m uncoated fused silica capillary with 25 mM HpS-,-CD in pH 2.50, 25 mM lithium phosphate as the separation buffer with detection at 220 nm. Application of reverse polarity at ,30 kV results in an elution time of about 12 min for PHA-543613 and 13 min for the undesired S -enantiomer. Quantification is versus an authentic reference S -enantiomer as an external standard in combination with an internal standard. The procedure was validated over the range 0.1,2.0% w/w. The detection limit is 0.01,0.02%. The amount of distomer intrinsic to the drug substance is about 0.1% or less. The developed method was used to generate stability data on multiple lots: in one case for up to 3 years. [source] Use of evaporative light scattering detector in the detection and quantification of enantiomeric mixtures by HPLCJOURNAL OF SEPARATION SCIENCE, JSS, Issue 10 2006Tong Zhang Abstract Routinely used in our laboratories at analytical scale, an evaporative light scattering detector (ELSD) has proved to be versatile in the detection of enantiomeric resolution using chiral stationary phases by HPLC. Though this kind of detector has been widely used in various domains, its application in enantiomeric resolution has not been discussed in the literature and is found to have very specific features especially in the quantitative perspective. In contrast with the UV detection, the peak area from ELSD for both enantiomers of a racemic mixture may not be the same. This complicates the assessment of the enantiomeric purity of unknown samples. This current work deals with some practical aspects in the detection of enantiomers and in accurate quantitative determination of enantiomeric purity by ELSD. Effects of analyte nature (more precisely molecular weight and volatility), peak shape and peak shape difference between enantiomers on the quantitative integration by ELSD are discussed in connection with the UV-detection results. The calibration for quantitative enantiomeric analysis and its effectiveness are demonstrated. [source] Study on the enantiomeric ratio of the pharmaceutical substances alkannin and shikoninBIOMEDICAL CHROMATOGRAPHY, Issue 10 2004A. N. Assimopoulou Abstract The chiral pair alkannin and shikonin (A/S) are potent pharmaceutical substances with a wide spectrum of biological activity; their enantiomeric ratio does not in,uence the major biological activity studied hitherto. Nevertheless, in pharmaceutical development and approval of chiral drugs from the Health and Regulatory Authorities, full documentation of methods of analysis of enantiomeric drugs, is required in order to evaluate the enantiomeric purity of starting materials and ,nal products and to control the stability of enantiomers in pharmaceutical formulations under several experimental conditions. In the present study, the enantiomeric ratio of A/S was determined in several commercial samples of alkannin and shikonin and also the proportion of A/S derivatives in several Alkanna root samples, which are all used as active ingredients in pharmaceuticals. Light and air proved not to in,uence the enantiomeric ratio of A/S on a shikonin commercial sample, and temperature also did not alter the A/S ratio on shikonin and alkannin commercial samples. Microencapsulation of alkannin and shikonin commercial samples in ethylcellulose microspheres and also molecular inclusion of a shikonin commercial sample in , -hydroxypropyl-cyclodextrin, which are used as drug delivery systems, did not alter the A/S enantiomeric ratio. Copyright © 2004 John Wiley & Sons, Ltd. [source] Enantioselective synthesis and antioxidant activity of 3-(3,4-dihydroxyphenyl)-glyceric acid,Basic monomeric moiety of a biologically active polyether from Symphytum asperum and S. caucasicumCHIRALITY, Issue 8 2010Maia Merlani Abstract The racemic and enantioselective synthesis of a novel glyceric acid derivative, namely, 2,3-dihydroxy-3-(3,4-dihydroxyphenyl)-propionic acid as well as the antioxidant activities is described. The virtually pure enantiomers, (+)-(2R,3S)-2,3-dihydroxy-3-(3,4-dihydroxyphenyl)-propionic acid and (,)-(2S,3R)-2,3-dihydroxy-3-(3,4-dihydroxyphenyl)-propionic acid were synthesized for the first time via Sharpless asymmetric dihydroxylation of trans-caffeic acid derivatives using the enantiocomplementary catalysts, (DHQD)2 -PHAL and (DHQ)2 -PHAL. The determination of enantiomeric purity of the novel chiral glyceric acid derivatives was performed by high-performance liquid chromatographic techniques on the stage of their alkylated precursors. The novel glyceric acid derivatives show strong antioxidant activity against hypochlorite and N,N -diphenyl- N -picryl-hydrazyl free radical. Their antioxidant activity is about 40-fold higher than that of the corresponding natural polyether and three-fold higher of trans-caffeic acid itself. Chirality, 2010. © 2010 Wiley-Liss, Inc. [source] Molecular tweezers for enantiodiscrimination in NMR: Di-(R,R)-1-[10-(1-hydroxy-2,2,2-trifluoroethyl)-9-anthryl]-2,2,2-trifluoroethyl benzenedicarboxylates,CHIRALITY, Issue 6 2010Sergio Gil Abstract A series of new chiral molecular tweezers, di-(R,R)-1-[10-(1-hydroxy-2,2,2-trifluoroethyl)-9-anthryl]-2,2,2-trifluoroethyl phthalate (2), isophthalate (3) and terephthalate (4), were synthesized and their structure studied by NMR and molecular mechanics. Their effectiveness as chiral solvating agents for the determination of the enantiomeric purity of chiral compounds using NMR was demonstrated. Chirality 2010. © 2009 Wiley-Liss, Inc. [source] Use of (S)-BINOL as NMR chiral solvating agent for the enantiodiscrimination of omeprazole and its analogsCHIRALITY, Issue 5 2010Jordi Redondo Abstract The application of (S)-1,1,-binaphthyl-2,2,-diol as NMR chiral solvating agent (CSA) for omeprazole, and three of its analogs (lanso-, panto-, and rabe-prazole) was investigated. The formation of diastereomeric host,guest complexes in solution between the CSA and the racemic substrates produced sufficient NMR signal splitting for the determination of enantiomeric excesses by 1H- or 19F-NMR spectroscopy. Using of hydrophobic deuterated solvents was mandatory for obtaining good enantiodiscrimination, thus suggesting the importance of intermolecular hydrogen bonds in the stabilization of the complexes. The method was applied to the fast quantification of the enantiomeric purity of in-process samples of S -omeprazole. Chirality, 2010. © 2009 Wiley-Liss, Inc. [source] High-performance liquid chromatography separation of enantiomers of mandelic acid and its analogs on a chiral stationary phaseCHIRALITY, Issue 5 2010Ritu Aneja Abstract The enantiomers of mandelic acid and its analogs have been chromatographically separated on a chiral stationary phase (CSP) derived from 4-(3,5-dinitrobenzamido) tetrahydrophenanthrene. The rationale of separations of these compounds is discussed with respect to the method development for determining enantiomeric purity and possibility of obtaining enantiomerically pure materials by high-pressure liquid chromatography. The relationship of analyte structure to the extent of enantiomeric separation has been examined and separation factors (,) are presented for various groups of structurally related compounds. Chiral recognition models have been suggested to account for the observed separations. These models provide mechanistic insights into the chiral recognition process. Chirality 2010. © 2009 Wiley-Liss, Inc. [source] Parallel SFC/MS-MUX screening to assess enantiomeric purityCHIRALITY, Issue 8 2008Derek B. Laskar Abstract Enantiomeric excess (ee) was evaluated for two internally synthesized compound libraries using a high-throughput automated, intelligent four-channel parallel supercritical fluid chromatography/mass spectrometry system equipped with a multiplexed ion source interface (SFC/MS-MUX). The two libraries contained compounds spanning a wide range of enantiomeric ratios with structurally diverse chemical scaffolds and stereogenic centers. The system analyzed each sample simultaneously against four chiral columns using up to six organic modifiers. Enhancements to our previously published parallel supercritical fluid chromatography/mass spectrometry system were implemented to address the challenges associated with automated trace enantiomer identification and quantitation. A reversal of enantiomer elution order was observed for several samples across multiple CSPs and modifiers. The relationship between elution order and % ee accuracy is presented for compounds exhibiting high, middle and low % ee values. Despite incidences in which the minor enantiomer eluted prior to the major enantiomer with less than baseline resolution, the overall % ee was in agreement with separations in which full baseline resolution was achieved. The methods presented here demonstrate the value and utility of high-throughput ee determinations to support drug discovery and development programs. Chirality, 2008. © 2008 Wiley-Liss, Inc. [source] Chiral NMR discrimination of amines: Analysis of secondary, tertiary, and prochiral amines using (18-crown-6)-2,3,11,12-tetracarboxylic acid,CHIRALITY, Issue 3-4 2008Ann E. Lovely Abstract Enantiomeric discrimination is observed in the 1H and 13C NMR spectra of secondary and tertiary amines in the presence of (,)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (1). Nonequivalence of the resonances of prochiral nuclei in primary and secondary amines is also observed when they associate with 1. The amines are added in their neutral form and are protonated by the carboxylic acid groups of 1 to produce the corresponding ammonium and carboxylate ions. Secondary amines associate with 1 through two hydrogen bonds and an ion pair interaction. Tertiary amines can only form one hydrogen bond to accompany the ion pairing. Chiral discrimination in the 1H and 13C NMR spectra of a series of aryl-containing secondary amines is of sufficient magnitude to determine enantiomeric purities. The discrimination in the spectra of tertiary amines with 1 is smaller, but 13C NMR spectra provided enough distinction for the determination of enantiomeric purity. Chirality, 2008. © 2007 Wiley-Liss, Inc. [source] Sensitivity improvement of circular dichroism detection in HPLC by using a low-pass electronic noise filter: Application to the enantiomeric determination purity of a basic drugCHIRALITY, Issue 2 2007Marie Lorin Abstract The quality control of chiral drugs requires the determination of their enantiomeric purity. Nowadays, circular dichroism (CD) spectroscopy is gaining increasing importance in pharmaceutical analysis because of the commercially available CD detector in liquid chromatography. The separation of the two enantiomers of a basic drug (efaroxan) was achieved by high performance liquid chromatography using an amylose-derivated column with both UV and CD detections. A baseline-resolved separation (resolution: 5) was obtained after optimization of the mobile phase composition with hexane-ethanol-diethylamine (90:10:0.05; v/v/v). The use of a commercial low-pass electronic noise filter of the CD signal has improved the signal-to-noise ratio by a factor twelve and allowed the quantitation of each enantiomer in the 1.25,300 ,g ml,1 concentration range. The CD linear calibration curve, expressed in terms of stereoisomer height ratio versus concentration ratio, was plotted over the 0.4,6% range. A correlation coefficient greater than 0.999 was obtained by least-squares regression and the limit of detection for the distomer/eutomer ratio was estimated at 0.14%. Although the method validation showed good repeatability on the retention times (RSD < 0.9%), on the peak height ratios (RSD < 8.7%) of each enantiomer only up to 99.2% enantiomeric purity was achieved. Chirality, 2006. © 2006 Wiley-Liss, Inc. [source] Configurational stability of 2-benzoylcyclohexanone: Unexpected solvent effects on the rate of racemizationCHIRALITY, Issue 4 2005Gilbert E. Tumambac Abstract The kinetics of the racemization of 2-benzoylcyclohexanone 1 in hexanes, ethanol, and mixtures thereof have been investigated by time dependence of enantiomeric purity using enantioselective HPLC. In pure hexanes and ethanol, the racemization half-lives were determined as 552 and 23.8 min, respectively, at 66°C. Surprisingly, racemization of 1 in mixtures of hexanes and ethanol was found to involve an induction period followed by a sigmoidal decrease of the enantiomeric excess with half-lives varying between 11.5 and 24.0 min. This unexpected solvent influence on the rate of racemization of 1 was attributed to complex isomerization mechanisms involving three possibly interconverting enol tautomers of 1.Chirality 17:171,176, 2005. © 2005 Wiley-Liss, Inc. [source] | ||||||||||