Enantiomer separations compounds

A. Mosandl, U. Hener, U. Hagenauer-Hener and A. Kuster mann, Stereoisomeric flavor compounds. 33. Multidimensional gas chromatography dkect enantiomer separation of -y-lactones from fr uits, foods and beverages , 7. Agric. Food Chem. 38 767-771 (1990). 

The stereochemistry of each enantiomer separated by the chiral HPLC has been studied after methanolysis of the epoxy ring. Examining the H NMR data of esters of the produced methoxyalcohols with (S)- and (R)-a-methoxy-a-(tri-fluoromethyl) phenylacetic acid by a modified Mosher s method [181], it has been indicated that the earlier eluting parent epoxides are (3S,4R)-, (6S,7R)-, and (9R,10S)-isomers (Table 7) [75, 76, 179]. The above three chiral HPLC columns show different resolution abilities but a different elution order is not observed. The resolution profile by the reversed-phase OJ-R column has been generalized with molecular shapes of the epoxy compounds considering the... 

The enantiomer separation capability of the cinchonan carbamate selectors and CSPs, respectively, is extremely broad what acidic compounds is concerned (success rate close to 100% if the acidic functional group is close to the chiral center). Hence... 

The broad and nearly universal applicability of the cinchonan carbamate CSPs for chiral acid separations is further corroborated by successful enantiomer separations of acidic solutes having axial and planar chirality, respectively. For example, Tobler et al. [124] could separate the enantiomers of atropisomeric axially chiral 2 -dodecyloxy-6-nitrobiphenyl-2-carboxylic acid on an C-9-(tert-butylcarbamoyl)quinine-based CSP in the PO mode with a-value of 1.8 and Rs of 9.1. This compound is stereolabile and hence at elevated temperatures the two enantiomers were interconverted during the separation process on-column revealing characteristic plateau regions between the separated enantiomer peaks. A stopped-flow method was utilized to determine the kinetic rate constants and apparent rotational energy barriers for the interconversion process in the presence of the CSP. Apparent activation energies (i.e., energy barriers for interconversion) were found to be 93.0 and 94.6 kJ mol for the (-)- and (-l-)-enantiomers, respectively. 

Desiderio, C., Aturki, Z., and Eanali, S., Use of vancomycin silica stationary phase in packed capillary electrochromatography I. Enantiomer separation of basic compounds. Electrophoresis, 22, 535, 2001. 

Recently, CE has been developed for the analysis of drug substances. It is not employed with great frequency for quality control (owing to inherent sensitivity issues), but on occasion, CE procedures can be employed when HPLC procedures have failed to adequately measure the impurities. CE is particularly useful for the separation of closely related compounds such as the diastereomers and enantiomers of compounds with more than one chiral center. Figure 1.8 illustrates the separation of the diastereomers quinine (QN) and quinidine (QD) and some impurities using CE [17]. 

Nowadays, derivatized cyclodextrins are the most common chiral selector in the direct GC enantiomer separation of flavors, fragrances, essential oils, pheromones and other natural, nature identical and synthetic volatile COmpounds.20.22,23,47,49-57... 

Mosandl A, Schubert V, Stereoisomeric flavor compounds XXXVII Enantiomer separation of l-alken-3-yl esters and their chirality evaluation from essential oils using multidimensional gas chromatography (MDGC),/ Essen Oil Res 2 121— 132, 1990. 

The low thermal stability and the volatility of some of the low molecular weight stationary phases restricted their general use. Therefore, thermally stable and nonvolatile polymeric chiral stationary phases were developed by coupling the diamide phase, via the amino functionality, to a statistical copolymer of dimethylsiloxane and (2-carboxypropyl)methylsiloxane of appropriate viscosity131. The fluid polymeric phase, referred to as Chirasil-Val (Table 2), exhibits excellent properties for the enantiomer separation of a variety of compound classes over a broad temperature range141142. 

Enantiomer separation by hydrogen-bonding stationary phases generally requires substrate derivatization. Hence versatile derivatization strategies have been devised124. In some cases, enantiomer separation on Chirasil-Val may be carried out without prior derivatization, e.g., for alcohols and bifunctional carbonyl compounds145. A survey on compound classes which have been separated into enantiomers is available128. 

Figure 20. Simultaneous enantiomer separation of various classes of compounds ( Schurig test mixture 184) on CP-Cyclodextrin-/3-2,3,6-M-19 (permethylatcd /3-cyclodextrin in OV-1701) [25 m x 0.25 mm (i.d.) column, 70°C for 5 min followed by 3cC/miu, 0.65 bar hydrogen]143. 1+2 2,6,6-trimethylbicy-clo[3.1.1]hept-2-ene (x-pinene), 3 ( + )-(lJR)-//ms-2,6,6-trimethylbicyclo[3.1. l]heptane (pinane), 4 (-)-(lS )-fra/M-pinanc. 5 (-)-(lS)-fw-pinane, 6 ( + )-(l/J)-cw-pinane, 7 + 8 2,3-butancdiol. 9 meso-2,3-butanediol, 10 + 11 tetrahydro-5-methyl-2-furanone (y-valerolactone). 12 + 13 1-phenylethanaminc. 14 + 15 1-phenylethanol, 16 + 17 2-ethylhexanoic acid.

MDGC is useful for separating compounds of an essential oil using two columns in line with different polarities. Through column-switching techniques, selected impure compounds in the first column can be diverted to the second column to ensure their complete separation. If the second column is chiral, then enantiomers potentially can be separated. The selected chiral stationary phase affects the resolution and separation drastically [73]. 

Mosandl, A., Hener, U., Hagenauer-Hener, U., and Kustermann, A. 1989. Stereoisomeric flavor compounds. XXXII. Direct enantiomer separation of chiral y-lactones from food and beverages by multidimensional gas chromatography. J. HighResolut. Chromatogr. 12 532-536. 

Recently, we have been investigating the chemistry of a series of racemic diquinoline compounds that form lattice inclusion hosts. The solid-state structures of these involve only rather weak intermolecular attractions. A number of these hosts assemble by means of centrosymmetric supramolecular synthons, and therefore their enantiomer separation is limited in the solid state. 

Figure 20 Top Preparative separation of the enantiomers of compound B (experimental conditions cf. text). Bottom Evidence of the high enantiomeric excess ee by using an analytical column coated with TBDMS-/3-CD in PS 86 (Schmidt et al., 2000).

In spite of important advances in asymmetric synthesis, chiral compounds cannot all be obtained in a pure state by asymmetric synthesis. As a result, enantiomer separation remains an important technique for obtaining optically active materials. Although asymmetric synthesis is a once-only procedure, an enantiomer separation process can be repeated until the optically pure sample is obtained. 

Enantiomer separation by inclusion complexation with a chiral host compound... 

Separation of a racemic compound has been called optical resolution or simply resolution . Nowadays, the descriptions enantiomer resolution or enantiomer separation are also commonly used. Accordingly, Enantiomer Separation is used in the title of this book. The editor and all chapter contributors hope that this book is helpful for scientists and engineers working in this field. 

Enantiomer separation of various compounds such as barbituric acids, benzoin, MTH-proline, glutethimide, a-methyl-oc-phenyl-succinimide, y-phenyl-y-butyrolac-tone, methyl-mandelate, l-(2-naphthyl)ethanol, mecoprop methyl, diclofop methyl and fenoxaprop methyl by pressure supported CEC on a permethyl-P-cyclodextrin modified stationary phase was described by Wistuba and Schurig [42-44]. Three different separation beds were used (i) permethyl-P-cyclodextrin was covalently attached via a thioether to silica (Chira-Dex-silica) [42], permethyl-P-cyclodextrin was linked to a dimethylpolysiloxane and thermally immobilized (ii) on silica (Chirasil-Dex-silica) [43] or (iii) on a silica monolith (Chirasil-Dex-monolith) [44], respectively. 

Efforts to improve the separation of closely related compounds are a frequent reason for using derivatives, and their application often makes it possible to separate compounds that otherwise cannot be separated. Chapter 5 gives various examples of this type, of which the separation of enantiomers of alcohols (p.90), carboxylic acids (p.125), amino acids (p.146) etc., are the most illustrative. The separation of sterols that differ in the position of the hydroxyl group may serve as another example. Isomers with a hydroxyl group in the a-position are not separated from 0-isomers on non-polar columns. However, if the hydroxyl group is converted into a suitable derivative, the two isomers can be separated well even on non-polar columns. The anomers of sugars can also be separated after their conversion into derivatives. 

In fact, the chemists working on these compounds wanted only one enantiomer of the irons epoxide—the top left stereoisomer. They were able to separate the trans epoxide from the cis epoxide by chromatography, because they are diastereoisomers. However, because they had made both diastereoisomers in the laboratory from achiral starting materials, both diastereoisomers were racemic mixtures of the two enantiomers. Separating the top enantiomer of the trans epoxide from the bottom one was much harder because enantiomers have identical physical and chemical properties. To get just the enantiomer they wanted the chemists had to develop some completely different chemistry, using enantiomerically pure compounds derived from nature. 

Cyclodextrins (CDs) are chiral compounds which interact with enantiomers via diastereomeric interactions. The separation is achieved because of the difference in stabilities of the resulting diastereomeric complexes formed between each enantiomer and the CD. In the first CEC experiments incorporating CDs, di-methylpolysiloxane containing chemically bonded permethylated (3- or y-CD (Chirasil-DEX) was chemically bonded to the inner walls of fused silica capillaries [139,140]. Electoosmotic flow is generated in these capillaries in the same manner as in fused silica capillaries. The Chirasil-DEX does not mask all the silanol groups, so while EOF is decreased, it is not entirely diminished by the coating. Since that time, CDs or CD derivatives have been bonded to silica particles which were then packed into capillaries, and the CD has been incorporated into continuous polymer beds known as monoliths. Table 3 shows some different CSPs, enantiomers separated, resolution, and the number of theoretical plates per meter. 

---