Comparison of different heptakis(6-O-alkyldimethylsilyl-2-3-di-O-ethyl)-β-cyclodextrins as chiral stationary phases in capillary GC

Three new β-cyclodextrin derivatives, heptakis(6-O-isopropyldi-methylsilyl-2,3-di-O-ethyl)-β-cyclodextrin, heptakis(6-O-thexyldi-methylsilyl-2,3-di-O-ethyl)-β-cyclodextrin, and heptakis(6-O-cy-clohexyldimethyl-2,3-di-O-ethyl)-β-cyclodextrin (IPDE-β-CD, TXDE-β-CD, and CHDE-β-CD), were synthesized and the enan-tioselectivities of these three CD derivatives and heptakis(6-O-tert-butyldimethylsilyl-2,3-di-O-ethyl)-β-cyclodextrin (TBDE-β-CD) were compared for GC separation of a range of chiral test com-pounds. In particular TXDE-β-CD showed much higher enentio-selectivity than TBDE-β-CD. Enentioselectivities of IPDE-β-CD and CHDE-β-CD are somewhat lower than that of TXDE-β-CD and CHDE-β-Cd are somewhat lower than that of TXDE-β-CD. These observations are indicative of significant effects of subtle changes in the structure of the 6-O-substituent on the enantioselec-tivity of the β-CD derivatives. The difference in enantioselectivities of the 6-O-substituted CD derivatives were explained in terms of relative contributions of the effects of hydrophobicity and steric hindrance of the substituent to the inclusion process. CHDE-β-CD showed the lowest enantioselectivity among the threederivatives. It is likely that the unfavorable steric hindrance of the bulky cyclo-hexyl group plays a greater role than the favorable hydrophobicity effect of the cyclohexyl group in the inclusion process in CHDE-β-CD. IPDE-β-CD showed lower selectivity than TXDE-β-CD and TBDE-β-CD. In the case of these CD derivatives having acyclic substituents the relative hydrophobicity of the substituent seems to be a dominant factor affecting the inclusion process. Isopropyl groups factor affecting the inclusion process. Isopropyl groups are less hydrophobic than thexyl and tert-butyl groups.     

γ(δ)-Thionolactones – Enantioselective Capillary GC and Sensory Characteristics of Enantiomers

The even numbered γ(δ)-thionolactones (C₆–C₁₂) were investigated, using heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)- and heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin as chiral stationary phases in capillary gas chromatography. The odor characteristics of γ(δ)-thionolactone enantiomers were investigated by enantioselective gas chromatography/olfactometry.     

Stereoisomeric flavor compounds,part LVIII: The use of heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin as a chiral stationary phase in flavor analysis

The characteristics of the new chiral stationary phase heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin are outlined and compared with permethyl- and perethyl-β-cyclodextrins.     

Stereochemical differentiation and simultaneous analysis of 3-, 4-, and 5-hydroxyalkanoic acids from biopolyesters by multidimensional gas chromatography

The direct enantioselective analysis of 3-, 4-, and 5-hydroxy fatty acids from biological material has been achieved by enantioselective multidimensional gas chromatography (enantio-MDGC) with heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)- or (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin as chiral stationary phase. All the bacteria investigated produced polyesters of enatiomerically pure (R) configured compounds.     

New,selectively substituted cyclodextrins as stationary phases for the analysis of chiral constituents of essential oils

New β- and γ-cyclodextrin derivatives, selectively substituted with n-pentyl and methyl groups, e.g. heptakis(2,6-di-O-methyl-3-O-pentyl)-β-cyclodextrin, octakis(2-O-methyl-3,6-di-O-pentyl)-γ-cyclodextrin, and octakis(2,6-di-O-methyl-3-O-pentyl)-γ-cyclodextrin, have been prepared from specifically protected intermediates. The new cyclodextrin derivatives exhibit unique enantioselectivity towards important chiral constituents of essential oils. The enantiomers of lavandulol, α-bisabolol, nerolidol, and other terpenoid alcohols could be resolved and their presence in different essential oils could be proved. Methyl jasmonate and epi-methyl jasmonate could, in addition, be detected in jasmine concrete by two-dimensional gas chromatography. The enantiomers of the macrocyclic ketone muscone have been separated for the first time.     

Enantiomeric composition of the chiral constituents in essential oils. Part 1: Monoterpene hydrocarbons

Using a dual column gas chromatograph equipped with two capillary columns coated with heptakis(6-O-methyl-2,3-di-O-pentyl)-β-cyclodextrin (6-me-2,3-pe-β-CD) and octakis(6-O-methyl-2,3-di-O-pentyl)-γ-cyclodextrin (6-me-2,3-pe-γ-CD), respectively, all important olefinic monoterpene hydrocarbons occurring in essential oils, including α-thujene, α- and β-pinene, camphene, sabinene, α- and β-phellandrene, Δ-3-carene and limonene can be resolved into enantiomers. With the chromatographic system described the characteristic enantiomeric composition of these monoterpene hydrocarbons in essential oils can be determined.     

Direct enantiomer separation of chiral γ-lactones from food and beverages by multidimensional gas chromatography

Chiral γ-lactones from the raw flavor extract of strawberries and some commercially available fruit-containing food and beverages were stereoanalyzed directly by multidimensional gas chromatography (MDGC) employing heart-cutting techniques from DB-1701 as the preseparation column onto heptakis (3-O-acetyl-2,6-di-O-pentyl)-β-cyclodextrin as the chiral stationary phase.     

七-(2,6-二-O-甲基)-β-环糊精对1,1'-联萘酚对映体手性识别的电喷雾质谱研究

利用电喷雾质谱研究了β-环糊精、七-(2,6-二-O-甲基)-β-环糊精作为手性识别试剂对1,1'-联萘酚对映体的手性识别效应. 实验结果表明, 在气相中, β-环糊精与七-(2,6-二-O-甲基)-β-环糊精都可以与联萘酚形成非共价复合物. 对形成的复合物的串联质谱研究表明, β-环糊精不能识别联萘酚对映体, 而七-(2,6-二-O-甲基)-β-环糊精对联萘酚对映体有较强的手性识别效应. 进一步研究表明七-(2,6-二-O-甲基)-β-环糊精与联萘酚对映体混合比例以及CID能量对于手性识别并无影响.     

Highly efficient NMR enantiodiscrimination of 1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane,a chiral degradation product of sevoflurane,by heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin

The molecular basis of the efficient enantiodiscrimination of 1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane, a chiral degradation product of the inhalation anaesthetic sevoflurane, using heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin as chiral selector, has been investigated by NMR spectroscopy. An interaction mechanism is proposed, which highlights the role of the functional groups on the β-cyclodextrin rims in addition to a partial molecular inclusion.     

Structural and thermodynamic investigations of an unusual enantiomeric separation: Lipodex E and compound B

Compound B (1,1,3,3,3-pentafluoro-2-fluoromethoxy-1-methoxypropane) can be separated by gas chromatography with an extraordinary chiral separation factor on a column coated with Lipodex E (octakis(3-O-butanoyl-2,6-di-O-n-pentyl)-γ-cyclodextrin). The enantioselectivity is greatly reduced when employing the β-cyclodextrin analogue. To further investigate the background of this unusual separation, the complexation between ‘compound B’ and Lipodex E (octakis(3-O-butanoyl-2,6-di-O-n-pentyl)-γ-cyclodextrin) and heptakis(3-O-butanoyl-2,6-di-O-n-pentyl)-β-cyclodextrin were studied by NMR. Association constants of the interaction of the two enantiomers of compound B with Lipodex E and its β-cyclodextrin analogue were determined by NMR chemical shift titration and showed a large difference corroborating earlier GC results. Heteronuclear NOE measurements proved that inclusion complex formation is taking place with compound B situated inside the cavity of the cyclodextrin moiety. Differences between the inclusion complex structures and their connection to association constants are discussed.     

Extending the scope of enantiomer separation on diluted methylated β-cyclodextrin derivatives by high-resolution gas chromatography

High-resolution open-tubular columns coated with solutions of heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (Phase I) or heptakis(2,6-di-O-methyl-3-O-trifluoroacetyl)-β-cyclodextrin (Phase II) in moderately polar polysiloxanes such as OV-1701 (5% cyanopropyl/7% phenyl/88% methylpolysiloxane) and OV-225 (25% cyanopropyl/50% phenyl/25% methylpolysiloxane) are used for the gas chromatographic enantiomer separation of volatiles belonging to different classes of compounds. No derivatization procedures are necessary for most of the resolved chiral molecules. The chiral stationary phases can be operated between 25 and 190°C for extended periods of time. The enantiomer separation of saturated, unfunctionalized hydrocarbons clearly demonstrates the importance of molecular inclusion in chiral recognition using cyclodextrins for this class of compounds. The different, and in some cases complementary, selectivity of the Phases I and II is demonstrated.     

Diluted modified cyclodextrins as chiral stationary phases – influence of the polysiloxane solvent: Heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin

The influence of different polysiloxane solvents on the efficiency and stereoselectivity of columns coated with mixtures of heptakis (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin and the polysiloxanes was investigated. Generally, the enantioselectivity increased with decreasing polarity of the silicone solvent and/or increasing cyclodextrin concentration, with some exceptions. Thermodynamic investigations showed that a change of the diluting phase or the cyclodextrin concentration affects entropy as well as enthalpy differences between the diastereomeric cyclodextrin/solute complexes. As a consequence, a certain cyclodextrin/polysiloxane combination is superior to another only at a particular temperature.     

Determination of cyclodextrins and their derivatives by capillary electrophoresis with indirect UV and conductivity detection

A fast and simple capillary electrophoretic method suitable for the determination of native α-, β-, γ-cyclodextrins, their randomly substituted tert-butyl derivatives (average degree of substitution 3.8 – 4.4), heptakis (2,6-di-O-methyl)- and heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin was developed. Naphthyl-2-sulfonic acid (2-NSA), 3-iodobenzoic acid (3-IBA) and (1S)-1-phenylethylamine (PHEA) were tested as selective complex forming and UV absorbing background electrolyte additives. The composition of optimized background electrolyte for the separation of uncharged cyclodextrins and their derivatives was: 15 mM 3-iodobenzoic acid titrated with tris[hydroxymethyl]aminomethane to pH 8.0, 5% (v/v) of acetonitrile. A complete resolution of mono-2-O-, mono-3-O- and mono-6-O-carboxymethyl-β-cyclodextrin regioisomers was achieved in the optimized background electrolyte system: 40 mM PHEA titrated with 2-[N-morpholino]ethanesulfonic acid to pH 5.6. In addition to indirect UV detection a contactless conductometric detector was successfully utilized.     

Cyclodextrin derivatives for GC separation of racemic mixtures of volatile compounds. Part VIII: 2,6-di-O-methyl-3-O-pentyl-γ-cyclodextrin and 2,6-di-O-methyl-3-O-(4-oxo-pentyl)- and 2,6-di-O-pentyl-3-O-(4-oxo-pentyl)-β-and -γ-cyclodextrins

In pre vious papers, 2,6-di-O-methyl-3-O-pentyl-β-cyclodextrin (CD) was demonstrated to be successful in separating volatile compounds, while avoiding the drawbacks of 2,3,6-tri-O-methyl-O-methyl-β-CD in terms of column stability and operating temperature. Since a CD chiral selector of universal use has not yet been found, and at least two (or more) columns coated with different CD derivatives are therefore necessary for routine work, the performance of 2,6-di-O-methyl-3-O-pentyl-γ-CD, 2,6-di-O-methyl-3-O-(4-oxopentyl)-γ-CD, 2,6-di-O-pentyl-3-O-(4-oxo-pentyl)-β-CD, and 2,6-di-O-pentyl-3-O-(-4-oxo-pentyl)-γ-CD diluted in polysiloxanes for the separation of volatile compounds in aromas and essential oils will be illustrated; each column coated with each of the newly synthesized CD derivatives was evaluated by analyzing more than 150 different recemates with different structures.     

Stereoisomeric flavor compounds. Part LXV: Preparative resolution of the enantiomers of chiral dihydrofuranones by recycling chromatography

Preparative resolution of the enantiomers of several chiral dihydrofuranones, known to be important flavor compounds, has been achieved by combining the use of bonded β-cyclo-dextrin as chiral stationary phase with closed-loop recycling chromatography. The purity of the separated enantiomers has been determined by chirospecific capillary GC analysis, using heptakis(2,3-di-O-methyl-6-TBDMS)-β-cyclodextrin as the chiral stationary phase.     

Stereoisomeric flavor compounds,part LXI: Enantioselective analysis of aroma-relevant dihydrofuranones

The odor impression of the pure enantiomers of various chiral dihydrofuranones which are important flavor compounds has been evaluated by sniffing the well separated optical antipodes in the GC eluate from heptakis(2,3-di-O-methyl-6-TBDMS)-β-cyclodextrin as the chiral phase for capillary gas chromato-graphic separation. Liquid chromatographic separation has been achieved by the use of bonded β-cyclodextrin as the chiral stationary phase and methanol–water as eluent. Enantiomer separation in the latter was improved by addition of triethylammonium acetate to the eluent.     

The separation of enantiomers on modified cyclodextrin columns: Measurements and molecular modeling

The enantiomers of 2-chloropropionic acid methyl ester, cis-pinane, 2-bromoethylbenzene, 2-bromobutane, 2-hydroxybutane trifluoroacetyl ester, and styrene oxide have been resolved on an octakis-(3-O-butyryl-2,6-di-O-pentyl)-γ-cyclo-dextrin capillary column, and the separation of the styrene oxide enantiomers has also been studied on columns coated with octakis-(3-O-trifluoroacetyl-2,6-di-O-pentyl)-cyclodextrin, octakis-(2,3,6-tri-O-pentyl)-γ-cyclodextrin, heptakis-(3-O-trifluoroacetyl-2,6-di-O-pentyl)-β -cyclodextrin, and heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin. Thermodynamic parameters (ΔG, ΔH, and ΔS) were determined from variable temperature measurements. The inclusion complexes containing styrene oxide were also studied by molecular modeling techniques. It has been found that a combined molecular mechanics–molecular dynamics approach may be a valuable tool for rationalizing the qualitative trends observed in the experimental separation factors. For the inclusion complexes considered here it is shown that the orientation of the guest relative to the cyclodextrin host is determined by the size and polarity of the cyclodextrin.     

Optimisation of a Headspace Solid-Phase Micro- Extraction Procedure for the Determination of 2,4,6-Trichloroanisole and Various Related Compounds in Cork Washing Waste Water by Use of Gas Chromatography-Mass Spectrometry

This paper reports the use of an anionic cyclodextrin, heptakis(2,3-di-O-methyl-6-O-sulfato)-β-cyclodextrin (HDMS-β-CD), for chiral separations of pharmaceutical enantiomers by nonaqueous capillary electrophoresis (NACE). Enantiomer resolution was affected mainly by HDMS-β-CD concentration and the acidity of the background electrolyte (BGE). The effects of capillary length and applied voltage on enantiomer resolution were also investigated. Results showed that in a methanol solution of 20 mM phosphoric acid, 10 mM sodium hydroxide, and 10 mM HDMS-β-CD, seven anticholinergic drugs were separated to baseline but no chiral separation was obtained for three other similar drugs. NACE is suitable for routine, rapid separation of the enantiomers of pharmaceutical compounds.     

Copolymeric cyclodextrin polysiloxane stationary phases prepared from 6A,6C- and 6A,6D-dialkenyl-substituted β-cyclodextrin

The syntheses of four new β-cyclodextrin-hexasiloxane copolymers from heptakis(2,3-di-O-methyl)-β-cyclodextrin (2) by multi-step processes are described. 6^A,6^C-Di-O-[p,p'-methylenebis(benzenesulfonyl)]hetakis(2,3-di-O-methyl)β-cyclodextrin (3) , which was prepared by the reaction of 2 with p,p'-methylenebis-(benzenesulfonyl chloride), is a key intermediate for the preparation of permethylated 6^A,6^C-bisalkenyl-β-cyclodextrins 5, 6 , and 9. Permethylated 6^A,6^C-bissulfonate ester 4 , which was obtained from 3 by a methylation reaction under mild conditions, was reacted with sodium allyloxide or sodium ω-undecenyloxide to produce permethylated 6^A,6^C-bisallyl- (or bis-ω-undecenyl)-β-cyclodextrin 5 or 6 or was hydrolyzed with 2% sodium amalgam in methanol to yield diol 7. Compound 7 was oxidized with periodinane, followed by Wittig's reaction with methyltriphenylphosphonium iodide to give permethylated 6^A,6^C-dideoxy-6^A,6^C-dimethylene-β-cyclodextrin (9). Treatment of 2 with p,p'-methylenebis(benzenesulfonyl chloride) or p,p'-biphenyldisulfonyl chloride gave bissulfonate esters 10 or 11 , respectively. Both of them were treated with sodium p-allyloxy-phenoxide in DMF, followed by methylation, to form permethylated 6^A,6^D-di-O-(p-allyloxyphenyl)-β-cyclo-dextrin (16). Bisalkenes 5, 6, 9 and 16 were copolymerized with α,ω-dioctyldecamethylhexasiloxane by a hydrosilylation process to give the cyclodextrin-containing copolymers 17–20.     

Cyclodextrin carbamates as novel chiral stationary phases for capillary gas chromatography

The following carbamate derivatives of cyclodextrins (CDs) were prepared as novel chiral stationary phases for capillary gas chromatography: hexakis(2,6-di-O-pentyl)-α-cyclodextrin hexa(3-n-propyl, 3-isopropyl, and 3-phenylcarbamate), heptakis-(2,6-di-O-pentyl)-β-cyclodextrin hepta(3-n-propyl, 3-isopropyl, and 3-phenylcarbamate), and octakis(2,6-di-O-pentyl)-γ-cyclodextrin octa(3-n-propyl, 3-isopropyl, and 3-isopropyl, and 3-phenylcarbamate). Metal capillary columns coated with these stationary phases resolved many kinds of racemic mixture. In general, they were especially effective towards polar compounds such as free alcohols, amines, and epoxides. The types of sample which were effectively resolved depended on the cavity size of the CD: α-CD derivatives were specifically effective toward compounds having linear alkyl chains, and β-CD derivatives toward compounds with phenyl groups. The results indicate that chiral separation with the cyclodextrin carbamates depends on the formation of inclusion complexes and also on the hydrogen-bonding interactions between the samples and the CD carbamates.