Columns chiral

Chiral columns are packed with stereo-specific sorbents for the separation of stereoisomers in the sample.27 Many chiral columns operate in hydrophilic interaction mode (e.g., Pirkle-type) whereas others are used in reversed-phase mode (proteins, macrocyclic antibiotics, polysaccharides, etc.). The use of these columns is critical in the development of chiral drugs. Most chiral columns are quite expensive and many older chiral columns have low efficiencies and limited lifetimes. Examples of chiral separations are shown in Chapter 6. Alternately, convention columns can also be used for chiral separations using a chiral selector in the mobile phase.27 

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This experiment introduces the use of a chiral column (a 3-cyclodextrin-bonded Cjg column) to separate the beta-blocker drugs Inderal LA (S-propranolol and... 

Chiral Hplc Columns. There are about 40 commercially available chiral columns which are suitable for analytical and preparative purposes (57). In spite of the large number of commercially available chiral stationary phases, it is difficult and time-consuming to obtain good chiral separation. In order to try a specific resolution meaninghilly, a battery of chiral hplc columns is necessary and this is quite expensive. 

An hplc assay was developed suitable for the analysis of enantiomers of ketoprofen (KT), a 2-arylpropionic acid nonsteroidal antiinflammatory dmg (NSAID), in plasma and urine (59). Following the addition of racemic fenprofen as internal standard (IS), plasma containing the KT enantiomers and IS was extracted by Hquid-Hquid extraction at an acidic pH. After evaporation of the organic layer, the dmg and IS were reconstituted in the mobile phase and injected onto the hplc column. The enantiomers were separated at ambient temperature on a commercially available 250 x 4.6 mm amylose carbamate-packed chiral column (chiral AD) with hexane—isopropyl alcohol—trifluoroacetic acid (80 19.9 0.1) as the mobile phase pumped at 1.0 mL/min. The enantiomers of KT were quantified by uv detection with the wavelength set at 254 nm. The assay allows direct quantitation of KT enantiomers in clinical studies in human plasma and urine after adrninistration of therapeutic doses. 

Chiral separations have become of significant importance because the optical isomer of an active component can be considered an impurity. Optical isomers can have potentially different therapeutic or toxicological activities. The pharmaceutical Hterature is trying to address the issues pertaining to these compounds (155). Frequendy separations can be accompHshed by glc, hplc, or ce. For example, separation of R(+) and 5 (—) pindolol was accompHshed on a reversed-phase ceUulose-based chiral column with duorescence emission (156). The limits of detection were 1.2 ng/mL of R(+) and 4.3 ng/mL of 3 (—) pindolol in semm, and 21 and 76 ng/mL in urine, respectively. 

Optical resolution of the dithiirane 1-oxides 2 and 3 was accomplished by HPLC equipped with a chiral column (97T12203). Absolute configurations of 2a and 2b were determined by X-ray crystallography. Tire stereospecific isomerization (epimerrzation) of 2a to 3b and 2b to 3a was observed during the resolution study. 

GC using chiral columns coated with derivatized cyclodextrin is the analytical technique most frequently employed for the determination of the enantiomeric ratio of volatile compounds. Food products, as well as flavours and fragrances, are usually very complex matrices, so direct GC analysis of the enantiomeric ratio of certain components is usually difficult. Often, the components of interest are present in trace amounts and problems of peak overlap may occur. The literature reports many examples of the use of multidimensional gas chromatography with a combination of a non-chiral pre-column and a chiral analytical column for this type of analysis. 

Today, however, GC-GC coupling is seldom used to determine pesticides in environmental samples (2), although comprehensive MDGC has been applied to determine pesticides in more complex samples, such as human serum (19). On the other-hand, new trends in the pesticide market, which is now moving towards the production of optically active enantiomers and away from racemic mixtures, may make this area suitable for GC-GC application. The coupling of non-chiral columns to chiral columns appears to be a suitable solution to the separation problems that such a trend might cause. 

Recently, multidimensional GC has been employed in enantioselective analysis by placing a chiral stationary phase such as a cyclodextrin in the second column. Typically, switching valves are used to heart-cut the appropriate portion of the separation from a non-chiral column into a chiral column. Heil et al. used a dual column system consisting of a non-chiral pre-column (30 m X 0.25 mm X 0.38 p.m, PS-268) and a chiral (30 m X 0.32 mm X 0.64 p.m, heptakis(2,3-di-(9-methyl-6-(9-tert-butyldimethylsilyl)-(3-cyclodextrin) (TBDM-CD) analytical column to separate derivatized urinary organic acids that are indicative of metabolic diseases such as short bowel syndrome, phenylketonuria, tyrosinaemia, and others. They used a FID following the pre-column and an ion trap mass-selective detector following the... 

The enantioselective determination of 2,2, 3,3, 4,6 -hexachlorobiphenyl in milk was performed by Glausch et al. (21). These authors used an achiral column for an initial separation, followed by separation of the eluent fraction on a chiral column. Fat was separated from the milk by centrifugation, mixed with sodium sulfate, washed with petroleum ether and filtered. The solvent was evaporated and the sample was purified by gel permeation chromatography (GPC) and silica gel adsorption chromatography. Achiral GC was performed on DB-5 and OV-1701 columns, while the chiral GC was performed on immobilized Chirasil-Dex. 

Two chiral columns were also coupled to resolve three pairs of enantiomers simultaneously [29]. 

Each glycopeptide CSP has unique selectivity as well as complementary characteristics, and a considerable number of racemates have been resolved on all three of them. Interestingly, most of the resolved enantiomers have the same retention order on these macrocyclic CSPs. When they are mixed or coupled with each other, the selectivity on one CSP will not be canceled by another. Even if some compounds may not have the same retention order, the complementary effects will result in an identifiable selectivity. Therefore, the coupled chiral columns can be used as a screening tool and save chromatographers substantial time in method development. 

Based oil 11PLC analysis using a chiral column (Waters OptiPak TC). h Yield after purification by column chromatography. c Oxidative removal of the 2-isopropyl-4-methoxyphenyl moiety from 3 is unsuccessful. 

Racemic mixtures of sulfoxides have often been separated completely or partially into the enantiomers. Various resolution techniques have been used, but the most important method has been via diastereomeric salt formation. Recently, resolution via complex formation between sulfoxides and homochiral compounds has been demonstrated and will likely prove of increasing importance as a method of separating enantiomers. Preparative liquid chromatography on chiral columns may also prove increasingly important it already is very useful on an analytical scale for the determination of enantiomeric purity. 

The most direct method is the separation of the enantiomers by HPLC using chiral columns. It has the advantage that there is no risk of contamination from chiral resolving agents. The formation of diastereoisomers... 

Commercially available chiral columns such as CHIRACEL OD-R or Crest-Pak [14-16]. Such columns have, for example, been successfully used for the separation of the enantiomers of the bis-diimine [Ru[(N-N)2 (dmso)Cl] ] complexes [14,17,18]. 

The enantiomeric excess (ee) of the hydrogenated products was determined either by polarimetry, GLC equipped with a chiral column or H-NMR with a chiral shift reagent. Methyl lactate and methyl 3-hydroxybutanoate, obtained from 1 and 2, respectively, were analized polarimetry using a Perkin-Elmer 243B instrument. The reference values of [a]o(neat) were +8.4° for (R)-methyl pyruvate and -22.95° for methyl 3-hydroxybutcinoate. Before GLC analysis, i-butyl 5-hydroxyhexanoate, methyl 5-hydroxyhexanoate, and n-butyl 5-hydroxyhexanoate, obtained from 1, 5, and 6, respectively, were converted to the pentanoyl esters, methyl 3-hydroxybutanoate was converted to the acetyl ester, and methyl 4-methyl-3-hydroxybutanoate obtained from 2 was converted the ester of (+)-a-methyl-a-(trifluoromethyl)phenyl acetic acid (MTPA). 

In order to achieve a true comparison between both catalytic systems, colloidal and molecular, which display very different reaction rates, a series of experiments were carried out with the homogeneous molecular system, decreasing the catalyst concentration in the studied allylic alkylation reaction. The reaction evolution is monitored taking samples at different reaction times and analysing each of them by NMR spectroscopy (to determine the conversion) and HPLC chromatography with chiral column (to determine the enantioselectivity of I and II). For molecular catalyst systems, the Pd/substrate ratio was varied between 1/100 and 1/10,000. For the latter ratio, the initial reaction rate was found comparable to that of the colloidal system (Figure 2a), but interestingly the conversion of the substrate is quasi complete after ca. 100 h in... 

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