A mixed stationary phase containing two versatile cyclodextrin-based selectors for the simultaneous gas chromatographic enantioseparation of racemic alkanes and racemic alpha-amino acid derivatives

In an effort to simultaneously enantioseparate racemic unfunctionalized alkanes and racemic alpha-amino acid derivatives by gas chromatography (GC) in forthcoming experiments related to the search for extraterrestrial homochirality, the two versatile modified cyclodextrin (CD) selectors octakis(6-O-methyl-2,3-di-O-pentyl)-gamma-cyclodextrin (Lipodex G) and heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin were dissolved in a polysiloxane and the mixed binary chiral selector system was coated onto a 50m x 0.25 mm i.d. fused silica capillary column. Whereas the former CD selector enantioseparates racemic unfunctionalized alkanes the latter CD selector preferentially resolves N-(O,S)-trifluoroacetyl-alpha-amino acid alkyl esters. With both CD selectors employed as mixed binary chiral selector system present in one chiral stationary phase (CSP), the simultaneous gas chromatographic enantioseparation of racemic alkanes and of racemic derivatized alpha-amino acids is achieved in a single temperature-programmed run. Also for other classes of racemic compounds, the scope of enantioseparation could be extended as compared to the conventional use of the single CD selectors in GC.     

Stereoisomeric flavour compounds LXVIII. 2-, 3-, and 4-Alkyl-branched acids,part 2: Chirospecific analysis and sensory evaluation

Enantioselective GC analysis of 4-ethyloctanoic and 4-methylheptanoic acid, using heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin as the chiral stationary phase, is described and the sensory properties of several 4-alkyl-branched acids, using gas chromatography-olfactometry (GC-O) equipment and octakis(2,3-di-O-methyl-6-tert-butyldimethylsilyl)-γ-cyclodextrin as the stationary phase, are evaluated. The chirospecific analysis of various 2-, 3-, and 4-alkyl-branched acids from commercially available Roman chamomile (Chamaemelum nobile (L.) Allioni), Parmesan cheese, and subcutaneous mutton adipose tissue, using either GC-GC (MDGC) or GC-MS analytical methods, is described. © 1994 Wiley-Liss, Inc.     

Determination of the absolute configuration of secondary alcohols with Horeau's method including enantioselective gas chromatography

The reaction of optically active secondary alcohols with excess of racemic 2-phenylbutyric acid anhydride in pyridine proceeds at different rates to the diastereoisomeric esters (kinetic partial resolution). According to Horeau the (unknown) absolute configuration of the alcohol can be derived from the optical rotation of the remaining excess of 2-phenylbutyric acid in the reaction mixture. Measuring the optical rotation may be very difficult in cases of small absolute rotation values and may be inaccurate due to the necessity to completely remove all chiral impurities. The application of Horeau's method is greatly facilitated by gas chromatographic determination of the enantiomeric ratio of the remaining 2-phenylbutyric acid after methylation using a short capillary column with heptakis(2,6-di-O-methyl-3-O-pentyl)-β-cyclodextrin as a chiral stationary phase. Baseline resolution of the enantiomers is achieved after approximately 10 min of retention time. Due to the high selectivity of capillary gas chromatography the probability of impurities in the mixture to interfere with the measurement of the enantiomeric ratio is extremely low. © 1994 Wiley-Liss, Inc.     

Substituent effects on chiral resolutions of derivatized 1‐phenylalkylamines by heptakis(2,3‐di‐O‐methyl‐6‐O‐tert‐butyldimethylsilyl)‐β‐cyclodextrin GC stationary phase

Chiral resolutions of trifluoroacetyl‐derivatized 1‐phenylalkylamines with different type and position of substituent were investigated by capillary gas chromatography by using heptakis(2,3‐di‐O‐methyl‐6‐O‐tert‐butyldimethylsilyl)‐β‐cyclodextrin diluted in OV‐1701 as a chiral stationary phase. The influence of column temperature on retention and enantioselectivity was examined. All enantiomers of meta‐substituted analytes as well as fluoro‐substituted analytes could be resolved. Temperature had a favorable influence on enantioselectivity for small amines with substituents at the ortho‐position. The type of substituent at the stereogenic center of amines also had a crucial effect as the ethyl group led to poor enantioseparation. Among all analytes studied, trifluoroacetyl‐derivatized 1‐(2′‐fluorophenyl)ethylamine exhibited baseline resolution with the shortest analysis time.     

Stereoisomeric flavour compounds XXXV: Chiral aroma compounds of sherry I. Optically pure stereoisomers of solerone and solerole

The enantioseparation of the sherry aroma components 5-oxo-4-hydroxyhexanoic acid γ-lactone (solerone) and 4,5-dihydroxyhexanoic acid γ-lactone (solerole) is achieved, using Chiraspher (Merck) as the chiral HPLC phase and the optical purity ascertained directly by HRGC with heptakis(3-O-acetyl-2,6-di-O-pentyl)-β-cyclodextrin (Lipodex D) as the chiral stationary phase. The absolute configurations of 4,5-dihydroxyhexanoic acid γ-lactones are assigned by ¹H-NMR spectral data of diastereomeric α-methoxy-α-trifluoromethylphenylacetic acid (MTPA) esters, according to Mosher's model. Sensory qualities of the isomers are given.     

Gas chromatographic separation of PCB atropisomers on cyclodextrin stationary phases

Gas chromatographic study on chiral separation of PCBs was performed in a series of capillary columns coated with 0.1-μm film of modified cyclodextrin (CD) stationary phases. The preparation of columns included the investigation into the effect of the content of cyclodextrin derivative in polysiloxane, the type of polysiloxane and temperature of analysis on the quality of separation and retention of atropisomers of 15 selected PCB congeners. The separation properties towards PCBs of stationary phase heptakis(2,3-di-O-methyl-6-O-tert-butyl-dimethylsilyl)-β-CD dissolved in SE-30, SE-54, and OV-1701, were compared with those of 6-monokis-octamethylene-permethyl-β-CD anchored to polydimethylsiloxane polymer (ChirasilDex column, Chrompack, Middelburg, The Netherlands) and octakis(2,6-di-O-methyl-3-O-pentyl)-γ-CD in OV-1701 (MEGA, Legnano (MI), Italy). The correctness of quantitative enantiomer ratio determination was assesed by splitless analysis of PCBs reference solutions in concentration of 1.25–125 ng/ml (PCBs 45 and 91) and 2.5–250 ng/ml (PCB 95) (the PCB congeners are numbered according to IUPAC). Chirality 10:540–547, 1998. © 1998 Wiley-Liss, Inc.     

Application of force field calculations to the prediction of chirally discriminating chromatographic behaviour for β-CDs

β-Cyclodextrin and its derivatives have been utilised to effect chiral separation in HPLC and CZE, both as stationary phases and mobile phase additives. The basis of the method is assumed to depend upon the formation of inclusion complexes of differing stabilities between enantiomeric analytes and the cyclodextrin, resulting in a differential dynamic distribution between chromatographic phases. In this study, force field calculations have been employed to model the inclusion complexes of enantiomeric brompheniramine, ephedrine, pseudoephedrine, ibuprofen, mandelic acid, methylphenobarbitone, and hexobarbitone with β-cyclodextrin. The resulting values for Δ(ΔH), the difference in enthalpy of complex formation between enantiomeric pairs has been compared with literature chromatographic data to explain the ability of the systems to achieve enantiomeric separations. © 1996 Wiley-Liss, Inc.     

Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin combining cinchona alkaloid moiety

Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated β-cyclodextrin (β-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than β-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of β-CD moiety, which lead to the different enantioseparation of β-CD-QN-based CSP and β-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding β-CD-based CSP for certain samples.     

Cyclodextrin derivatives in GC separation of racemic mixtures of volatiles: Part III

The gas chromatographic performance of differently derivatized α-, β-, and γ-cyclodextrins in the separation of racemic mixtures of volatiles is investigated. The performances of 2,3,6-permethylated α-, β-, and γ;-cyclodextrins and 2,6-dimethyl-3-trifluoro-acetyl α-, β-, and γ-cyclodextrins mixed with different ratios of OV-1701 or OV-1701-OH terminated were tested with racemates with widely differing structures. The influence of the percentage of cyclodextrins in polysiloxane, of film thickness of the stationary phase, of the length of the column, of column conditioning, and of the operating temperatures in the separations of different racemates has been evaluated.     

Gas chromatographic enantioseparation of unfunctionalized chiral alkanes: a challenge in separation science (overview, state of the art, and perspectives)

The chromatographic enantioseparation of small unfunctionalized chiral alkanes C*HR(1)R(2)R(3) (R = alkyl) represents a challenge in separation science. Because of the lack of any functional groups, enantiorecognition in the presence of a chiral selector is solely based upon weak enantioselective Van der Waals forces. Racemic alkanes containing seven and eight carbon atoms, i.e. 3-methylhexane (C7), 2,3-dimethylpentane (C7), 3-methylheptane (C8), 3,4-dimethylhexane (C8), 2,4-dimethylhexane (C8), 2,3-dimethylhexane (C8), and 2,2,3-trimethylpentane (C8) have been gas chromatographically enantioseparated on different modified cyclodextrins. The substitution pattern and cavity size of the cyclodextrin selectors have a pronounced effect on the degree of enantiorecognition observed. Thermodynamic parameters of enantiorecognition between four chiral alkanes and octakis(6-O-methyl-2,3-di-O-pentyl)-gamma-cyclodextrin (Lipodex G) have been determined. The possible role of molecular inclusion is indicated by the complete loss of enantioselectivity when the cyclodextrins are replaced by the corresponding linear dextrins ("acyclodextrins"). The enantioseparations of all seven chiral C7-C8 alkanes, six of them simultaneously, has been achieved on mixed binary selector systems whereby two different modified cyclodextrins are present in one gas chromatographic column. The smallest chiral (nonisotopically labeled) allene, i.e., 2,3-pentadiene, has been resolved gas chromatographically on a cyclodextrin selector.     

(Z)-1,1-dichloro-2-(4-benzyloxyphenyl)-2,3-bis(4-methoxyphenyl)cyclopropane: The synthesis and enantiomeric separation of an antitumor agent

(Z)-1,1-Dichloro-2-(4-benzyloxyphenyl)-2,3-bis(4-methoxyphenyl)cyclopropane ( 5 ), a potential antitumor agent designed to treat breast cancer, was prepared in three steps. A stereospecific palladium-catalyzed cross coupling reaction which provided the intermediate (Z)-triaryl alkene 4 was a crucial step in the synthesis. Makosza phase transfer reaction on 4 gave the enantiomeric (Z)-dichlorocyclopropane derivatives 5 which were resolved by semipreparative HPLC on a chiral stationary phase consisting of amylose tris-3,5-dimethylphenyl carbamate coated on silica gel. © 1994 Wiley-Liss, Inc.     

Determination of the enantiomeric composition of mexiletine and its four hydroxylated metabolites in urine by enantioselective capillary gas chromatography

The enantiomers of mexiletine and four of its hydroxylated metabolites were directly separated by capillary gas chromatography using a heptakis(6-O-tert-butyl-dimethylsilyl-2,3-di-O-methyl)-β-cyclodextrin column. The method was applied to the analysis of urine samples from cancer patients who were treated with racemic mexiletine as part of a study of the use of mexiletine in the relief of neuropathic pain. Samples analyzed before and after deconjugation of the urine with β-glucuronidase/arylsulfatase showed a high stereoselectivity in the formation and conjugation of these compounds. © 1996 Wiley-Liss, Inc.     

Direct separation of albuterol enantiomers in biological fluids and pharmaceutical formulations using α1-acid glycoprotein and pirkle urea type columns

A direct, isocratic, and simple chromatographic method is described for the resolution of racemic albuterol using the α₁-acid glycoprotein chiral stationary phase (AGP-CSP) under reverse phase conditions. The effect of various organic modifiers, temperature, and phosphate buffer ionic strength on the separation factor (α) and stereochemical resolution factor (R_s) has been studied. The enantiomeric separation of albuterol was also achieved using a urea-type CSP of (S)-indoline-2-carboxylic acid and (R)-1-(α-naphthyl)ethylamine, known as Chirex 3022, running in the normal phase mode. The effect of different organic acids added to the mobile phase was examined and the chiral recognition mechanism(s) is discussed. Solid phase extraction with C₁₈ Sep-Pak cartridges was applied as a clean-up step to determine the enantiomeric ratio between (?)-R and (+)-S-albuterol in pharmaceutical formulations and in human plasma. © 1995 Wiley-Liss, Inc.     

Comparison between cellulose and amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phases for enantiomeric separation of 17 amidotetralins

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.     

Enantiomeric composition and prevalence of some bicyclic monoterpenoids in amber

Among the more prevalent chiral monoterpenoid compounds in conifers are α-pinene, β-pinene, and smaller amounts of camphene and limonene. The most prevalent chiral monoterpenoid compounds in fossilized resin (referred to as amber in this paper) appear to be borneol, isoborneol, and camphene. Most of these compounds have easily measured enantiomeric excesses. The borneol and isoborneol in some amber samples have pronounced enantiomeric excesses despite the fact that they are tens of millions of years old. The enantiomeric ratios of the monoterpenoids in different ambers vary tremendously and often are distinct. However, in any single amber sample, the stereochemistry (absolute configuration) of the excess monoterpenoid enantiomers appears to be identical. The camphene in amber may be a secondary reaction product formed over time, possibly from the dehydration of borneol. Although a compound's original stereochemistry can be preserved, it also may diminish with the number and type of chemical transformations over geological time. The monoterpene enantiomeric ratios in modern conifer resins vary tremendously. Future stereochemical studies are outlined that could provide the data necessary for more exact geochemical interpretations and possibly for obtaining pertinent paleobiological information. © 1996 Wiley-Liss, Inc.     

Enzymic Studies of the Distribution Pattern of 4-O-Methylglucuronic Acid Residues in Glucuronoxylans from Sunflower Hulls

Two epimers of methyl jasmonate were optically resolved by capillary gas chromatography, using heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin as the chiral stationary phase. In the tea volatile concentrates, both of these epimers were present as only one enantiomer, their absolute configurations being ascertained as (–)-(1R,2R)-methyl jasmonate and (+)-(1R,2S)-methyl epijasmonate.

The thermal isomerization of methyl epijamonate to methyl jasmonate was also clarified by optically resolved gas chromatography to have occurred at the asymmetric carbon of the C-2 position that is connected to the carbonyl group.     

Synthesis and analytical characterization of the sodium salt of heptakis(2-O-methyl-3,6-di-O-sulfo)cyclomaltoheptaose, a chiral resolving agent candidate for capillary electrophoresis

A pure, single isomer, strong electrolyte chiral resolving agent candidate for capillary electrophoresis, the sodium salt of heptakis(2-O-methyl-3,6-di-O-sulfo)cyclomaltoheptaose has been synthesized on the 100-g scale, in greater than 97% purity, through heptakis(2,6-di-O-tert-butyldimethylsilyl)cyclomaltoheptaose, heptakis(2-O-methyl-3,6-di-O-tert-butyldimethylsilyl)cyclomaltohep taose and heptakis(2-O-methyl)cyclomaltoheptaose intermediates. The structural identity of each intermediate and the final product was conclusively established by high-resolution MALDI-TOF mass spectrometry, variable-temperature 1H and 13C NMR spectroscopy and X-ray crystallography. The purity of each intermediate and the final product was determined by gradient high-performance liquid chromatography (HPLC) and indirect UV detection capillary electrophoresis.     

Determination of the enantiomeric purity of commercial Jacobsen's catalyst samples

A HPLC method is described for the chiral analysis of the commercially available Jacobsen's catalyst. A hydroxypropyl β-cyclodextrin stationary phase was used in conjunction with a nonaqueous, polar-organic mobile phase. The method can be applied to control the enantiomeric purity of the catalyst, which is of great importance for quality control of that product. High accuracy in the determination of trace levels of the unwanted enantiomer in the presence of large amounts of the desired enantiomer is demonstrated. Chirality 10:362–363, 1998. © 1998 Wiley-Liss, Inc.     

Group-Recognition Ability of Derivatized β-Cyclodextrin as Studied by the ESR Spin Probing Technique

The effect of modifying the entrance face of β-cyclodextrin on the inclusion of various functional groups in aminoxyl spin probes was determined by the use of heptakis (2,6-O-dimethyl)-β-cyclodextrin and heptakis (2,3,6-O-triacetyl)-β-cyclodextrin. The methylation of six of the secondary hydroxyl groups on the wider end of β-cyclodextrin has a variable effect on the association constant of inclusion depending on the nature of the included group. The role of the methoxy group on the rim is discussed on the basis of the thermodynamic data derived from association constants. Contrary to the unmodified β-cyclodextrin the pH of the solution does not influence the inclusion behaviour.     

Interactions of chiral molecules with an (r)-n-(3,5-dinitrobenzoyl) phenylglycine HPLC stationary phase

Forty different chiral molecules were studied by liquid chromatography with a Pirkle-type, (R)-N-(3,5-dinitrobenzoyl) phenylglycine (DNBPG), chiral stationary phase column. The dramatic effect of a small molecular change on chiral recognition was demonstrated using DL-amino acid derivatives. The inductive effect on chiral recognition was also studied using trifluoro-, trichloro-, dichloro-, monochloroacetyl, and acetyl derivatives of four different chiral amines. The study of the enantiomer separation of 11 different crown ethers of 2,2′-binaphthyldiyl showed that the rigidity of the chiral center can be an additional parameter in chiral recognition for the DNBPG phase but not for a β-cyclodextrin bonded chiral phase. It is apparent from this study that steric effects, inductive effects, and molecular rigidity play important roles in chiral recognition with DNBPG chiral stationary phases.