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.     

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.     

Enantiomeric composition of the chiral constituents of essential oils—part 3: Diterpene hydrocarbons

Enantiomeric diterpene hydrocarbons were isolated from different plants and identified by mass spectrometric and NMR investigations. All enantiomeric pairs could be resolved by capillary gas chromatography using either heptakis(2,6-di-O-methyl-3-O-pen-tyl)-β-cyclodextrin or heptakis(6-O-tert-butyldimethylsilyl-2,3-di-O-methyl)-β-cyclodextrin as chiral stationary phases.     

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.     

Stereoisomeric flavor compounds part. LV: Stereodifferentiation of some chiral volatiles on heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin

Heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclo -dextrin proves to be a versatile chiral stationary phase for the direct differentiation of aroma-relevant enantiomers.     

Partially Methylated β-Cyclodextrin Analysis: A Systematic Approach to Appropriate RP Column Selection

In order to establish guidelines to help the analyst in the choice of the most suitable octadecyl or octyl bonded phase for the LC analysis of a given partially methylated β-CD sample, analyses of four commercially available dimethyl-β-cyclodextrins (DM-β-CDs) have been carried out on nine octyl (C₈) or octadecyl (C₁₈) silica bonded or polymeric bonded phases which differ significantly in their hydrophilic and hydrophobic properties. Chromatograms show that the nature of the packing materials has considerable influence on the resolution of complex mixtures composed of closely related compounds such as partially methylated β-CDs. Among various kinds of C₈ and C₁₈ bonded phases, silica based and monomeric phases which present both reinforced hydrophobic and polar interactions showed the best performance. Whatever the complexity of the commercial DM-β-CD, the richest chromatographic fingerprints, which best depict the complexity of the mixture, are obtained with Nucleosil 50-5-C₈ column. For the simplest mixtures, Nucleosil 50-5-C₈ column with acetonitrile-water (34:66) as mobile phase is the most suitable chromatographic system and leads to the best resolution between heptakis (2,6-di-O-methyl)-β-CD and hexakis (2,6-di-O-methyl)-mono(2,3,6-tri-O-methyl)-β-CD (14 OCH₃ and 15 OCH₃). This chromatographic system might enable an LC-MS coupling for direct identification of the different components in the mixture as well as control of batch to batch variations.     

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.     

Stereoisomeric flavor compounds LXXVII: 3-Butylhexahydrophthalides: Simultaneous enantioselective analysis,structure elucidation,and sensorial properties of the stereoisomers

Using heptakis-(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cy-clodextrin as the chirul stationary phase in enantioselective gas chromatography, the simultaneous enantioselective analysis of all eight 3-butylhexahydrophthalide Stereoisomers was achieved. Fur-thermore, the odor characteristics and odor thresholds were investigated by enantioselective gas chromatography/olfactometry. Racemic standards were synthesized via hydrogenation and subsequent base catalyzed epimerization. Starting from racemic 3-butylphthalide. After separation by high performance liquid chromatography. Relative configurations of the pure diastereoisom-ers were determined by means of NOE-difference spectroscopy. The absolute configuration at C-3 was determined starting from (3S)-butylphthalide as an educt for hydrogenation and epimerization. Absolute configurations of all eight 3-butylhexahydrophtbalide stereoisomers are unambiguously concluded from the NOE-experi-ments in connection with the determination of the absolute configuration at C-3.     

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.     

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.     

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.     

Four oxoindole‐linked α‐alkoxy‐β‐amino acid derivatives

Four structures of oxoindolyl α‐hydroxy‐β‐amino acid derivatives, namely, methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐methoxy‐2‐phenylacetate, C₂₄H₂₈N₂O₆, (I), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐ethoxy‐2‐phenylacetate, C₂₅H₃₀N₂O₆, (II), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐[(4‐methoxybenzyl)oxy]‐2‐phenylacetate, C₃₁H₃₄N₂O₇, (III), and methyl 2‐[(anthracen‐9‐yl)methoxy]‐2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐phenylacetate, C₃₈H₃₆N₂O₆, (IV), have been determined. The diastereoselectivity of the chemical reaction involving α‐diazoesters and isatin imines in the presence of benzyl alcohol is confirmed through the relative configuration of the two stereogenic centres. In esters (I) and (III), the amide group adopts an anti conformation, whereas the conformation is syn in esters (II) and (IV). Nevertheless, the amide group forms intramolecular N—H...O hydrogen bonds with the ester and ether O atoms in all four structures. The ether‐linked substituents are in the extended conformation in all four structures. Ester (II) is dominated by intermolecular N—H...O hydrogen‐bond interactions. In contrast, the remaining three structures are sustained by C—H...O hydrogen‐bond interactions.     

Enantiomer separation by capillary SFC and GC on immobilized octakis(2,6-di-O-methyl-3-O-pentyl)-γ-cyclodextrin

Heptakis(2,6-di-O-methyl-3-O-pentyl) (2-O-methyl-6-O-oct-1-enyl-3-O-pentyl)-γ-cyclodextrin was immobilized to narrow-bore fused silica capillaries after selective modification. One tert-butyldimethylsilyl group was introduced into octakis-(2-O-methyl-3-O-pentyl)-γ-cyclodextrin in order to get a pure monofunctionalized cyclodextrin derivative. During synthesis the tert-butyldimethylsilyl group was replaced by an anchoring group to bind the cyclodextrin to a polysiloxane. After thermal immobilization of the modified polysiloxane this new chiral stationary phase was applied in GC and SFC. High efficiency separations were obtained in GC. In SFC very polar compounds could be chromatographed at low temperatures resulting in higher separation factors as compared to GC.     

Synthesis of propyl O-(α-L-rhamnopyranosyl)-(1→3)-[2,4-di-O-(2s-methylbutyryl)-α-L-rhamnopyranosyl]-(1→2)=(3-O-acetyl-β-D-glucopyranosyl)-(1→2)-βp-D-fucopyranoside,the tetrasaccharide moiety of Tricolorin A

Propyl O-(α-L-rhamnopyranosyl)-(1→3)-[2,4di-O-(2s-methylbutyryl)-α-L-rhamnopyranosyl]-(1→2)-(3-O-acetyl-β-glucopyranosyl)-(1→2)-β-D-fucopyranoside (1), the tetrasaccharide moiety of Ricolorin A, was synthesized in total 23 steps with a longest linear sequence of 10 steps, and overall yield of 3.7% from D-Glucose. The isomerization of the dioxolane-type benzylidene in the prance of NIS/AgOTf was observed. Tetrasaccharide 1 exhibited no activity against the cultured P388 cell as Tricolorin A did.     

Conformation of a terminally protected βγ hybrid dipeptide Boc‐Ant‐Gpn‐OMe stabilized by C6/C7 hydrogen bonds

The hybrid βγ dipeptide, methyl 2‐[1‐({2‐[(tert‐butoxycarbonyl)amino]benzamido}methyl)cyclohexyl]acetate (Boc‐Ant‐Gpn‐OMe), C₂₂H₃₂N₂O₅, adopts a folded conformation stabilized by intramolecular six‐ (C₆) and seven‐membered (C₇) hydrogen‐bonded rings, together with weak C—H...O and C—H...π interactions, resulting in a ribbon‐like structure.     

Gas chromatographic enantiomer separation of agrochemicals using modified cyclodextrins

The enantiomers of phenoxypropionic acid type herbicides have been resolved by capillary gas chromatography employing modified cyclodextrins as chiral stationary phases. Excellent separations were obtained with columns containing a 1:1 mixture of per-O-pentylated and per-O-methylated γ-cyclodextrin. The enantiomers of the methyl esters of mecoprop and dichlorprop were also resolved on octakis(3-O-butyryl-2,6-di-O-pentyl)-γ-cyclodextrin. On this phase the order of elution of the enantiomers was temperature-dependent, the elution order being reversed as the temperature passed through the isoenantioselective temperature. This is the first time such behavior has been observed with cyclodextrin derivatives. The enantiomers of the polychlorinated polycyclic pesticides cis- and trans-chlordane, oxychlordane, heptachlor, heptachlorepoxide, and three chiral organophosphorus pesticides could be resolved using selectively derivatized cyclodextrin derivatives.     

Nucleosides: Synthesis of Some New Naphthimidazole Ribonucleosides as Potential Antibacterial Agents

Reaction of 2-trifluoromethyl- or 2-cyanonaphth[2,3-d] imidazole (1 or 2) with 1-O-acetyl-2,3,5-tri-O- benzoyl-β-D-ribofuranose (3), using the triflate or fusion method afforded 2-trifluoromethyl-1-(2,3,5-tri- O-benzoyl-α-D- or -β-D-ribofuranosyl)naphth[2,3-d]imidazole (4 or 6) and 2-cyano-1-(2,3,5-tri-O-benzoyl-α-D- or β-D-ribofuranosyl)naphth[2,3,-d] imidazole (5 or 7), respectively. The products 4 and 5 or 6 and 7 were separated by chromatography on silica gel. Treatment of the blocked nucleosides 4-7 with methanolic NH₃ at 0 °C furnished the deblocked nucleosides 8-11 respectively. Treatment of 10 with 5% NH₃ (aq) at 60 °C gave 11. Structural elucidation is based on elemental analysis, UV, FAB-MS and ¹H NMR spectra. Compounds 4-11 were subjected to antibacteial testing. Compounds 5, 7 and 10 have significant activity against Staphylococous aureus (gram positive) and Esherichia coli (gram negative) bacteria, whereas the other tested compounds showed no significant activity.     

Synthesis of per-6-guanidinylated cyclodextrins

Reaction of per(6-amino-6-deoxy-2,3-di-O-methyl)-α-, β- and γ-cyclodextrins with N,N′-bis(tert-butoxycarbonyl)-N″-triflylguanidine and triethylamine in tetrahydrofuran gave per[6-N,N′-bis(tert-butoxycarbonyl)guanidino-6-deoxy-2,3-di-O-methyl]-α-, β- and γ-cyclodextrins, respectively. Subsequent cleavage of the protective groups with trifluoroacetic acid in dichloromethane afforded per(6-deoxy-6-guanidino-2,3-di-O-methyl)-α-, β- and γ-cyclodextrins in very good overall yields.     

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.