Racemates enantiomeric separations

Macaudiere et al. first reported the enantiomeric separation of racemic phosphine oxides and amides on native cyclodextrin-based CSPs under subcritical conditions [53]. The separations obtained were indicative of inclusion complexation. When the CO,-methanol eluent used in SFC was replaced with hexane-ethanol in LC, reduced selectivity was observed. The authors proposed that the smaller size of the CO, molecule made it less likely than hexane to compete with the analyte for the cyclodextrin cavity. 

Mixing the additive in the eluent used as a mobile phase can also modify the chromatographic system (dynamic modification), but the use of modified adsorbents has led to an improvement of resolution. Example works include that by Armstrong and Zhou [11], who used a macrocyclic antibiotic as the chiral selector for enantiomeric separations of acids, racemic drugs, and dansyl amino acid on biphenyl-bonded silica. 

The preparation of enantiomerically pure drugs is one factor that makes enantioselective synthesis and the resolution of racemic drugs (separation into pure enantiomers) active areas of research today. 

The phenylcarbamate derivative 23j also showed chiral recognition for many racemates in CDCI3 (Figure 3.38). Figure 3.39 shows the 1H NMR spectra of ( )-2-butanol in the absence and presence of 23j. In the case of secondary alcohols, such as 2-butanol, 2-heptanol, and 2-octanol, the methyl protons at the end of the longer chain and remote from the stereogenic center were enantiomerically separated in the presence of 23j, and the methine and... 

The data indicated that MCTA can be successfully applied for the enantiomeric separation of a wide variety of racemic pairs using aqueous organic mobile phases [137],... 

In contrast to Mori s synthesis, Pawar and Chattapadhyay used enzymatically controlled enantiomeric separation as the final step [300]. Butanone H was converted into 3-methylpent-l-en-3-ol I. Reaction with trimethyl orthoacetate and subsequent Claisen-orthoester rearrangement yielded ethyl (E)-5-methyl-hept-4-enoate K. Transformation of K into the aldehyde L, followed by reaction with ethylmagnesium bromide furnished racemic ( )-7-methylnon-6-ene-3-ol M. Its enzyme-catalysed enantioselective transesterification using vinylacetate and lipase from Penicillium or Pseudomonas directly afforded 157, while its enantiomer was obtained from the separated alcohol by standard acetylation. 

MPH is an amphetamine-like prescription stimulant commonly used to treat Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy in children and adults. LC/APCI-MS enantiomeric separations of racemic MPH (Ritalin ) were reported using a commercially available vancomycin CSP [111-113]. 

FIGURE 10 Capillary durability check for an enantiomeric separation in CE. An overlay of the 1st, 10th, 20th, 30th, 40th, and 50th electropherograms of consecutive injections of a racemic mixture for an intermediate product of nebivolol is presented. 

FIGURE I I Capillary-to-capillary reproducibility check for the same enantiomeric separation for the racemic mixture of an intermediate product of nebivolol. An overlay of three electropherograms performed on three different capillary lots is presented. 

Attachment of bulky chiral barriers to achieve enantiomeric selection is exemplified by ligands (61),204 (63)69 and (64).19 Ligands of type (61) are especially efficient chiral compounds with binap-thyl hinges . The orientation of the binaphthyl rings for (61) is shown more explicitly in (62).234 With optically pure (61), complete enantiomeric separation of ammonium salt racemates such as (67) is obtained.235-237 The structure has been determined crystallographically for the less stable d form of the PF6- salt of (67) with the (S,S) host (61). The results indicate that the receptor, substrate, counterion and solvent have undergone several steric concessions in order to relieve the strain imposed on the system by the visit of an unwanted guest.238... 

Enantiomeric separation is a great challenge. Every separation requires a dedicated column. Some packings are more able to separate many racemates. When a chiral selector is used as the stationary phase, the primary retention mechanism is complexation with the surface-... 

The enantiomeric separation of the D- from the L-stereoisomers of amino acids is an area of growing interest. It is generally recognized that heat- and alkali-treatment of proteins can result in the racemization of L-isomers of amino acid residues to the D-analogs. Almost without exception, humans cannot utilize the D-isomers of amino acids, and some are thought to be toxic (although... 

Enantiomeric separation 261 Racemic mixtures of tryptophan and thiophenal investigated in microfluidic-based membrane chromatography... 

Finally, we would like to describe the enantiomeric separation of racemic methyl phenyl sulfoxide by the dipeptide (1). Optically active sulfoxides are utilized as a... 

A suspension of the dipeptide (1) (1 mmol) in water (2 ml) was stirred together with racemic methyl phenyl sulfoxide (2 mmol) at room temperature for one day. The formed inclusion compound was collected by filtration and washed with water (20 ml) and dichloromethane (20 ml). From the inclusion compound, we recoverd the included methyl phenyl sulfoxide by extraction with dichloromethane to give (/ )-methyl phenyl sulfoxide. The dipeptide (1) remained as a solid. When the recovered dipeptide (1) was again subjected to the formation of inclusion compound with racemic methyl phenyl sulfoxide, (A1 (-methyl phenyl sulfoxide was obtained as summarized in Table 5. Thus, it was shown that the dipeptide (1) can be used repeatedly for enantiomeric separation of methyl phenyl sulfoxide. 

Figure 3. Analytical enantiomeric separation of methyloxirane on EU-CAM3 by complexa-tion GC (center). Racemic sample spiked with (Rj-enantiomer (left) and with (S)-enantiomer (right). Experimental conditions cf. text. (R -methyloxirane elutes after 9 min (Golding et al., 1977).

The presence of water was subsequently identified as being essential for the performance of the above set-up and for maintaining high enantiose-lectivity (Lindstrom et al., 1990). The preparative-scale enantiomeric separation of racemic camphene with a separation factor as high as a — 3.7 (measured at 30°C on an analytical column) was subsequently achieved at 45°C on a 2.1 m x 4 mm (i.d.) column containing a-cyclodextrin hydrate in formamide (1 5, w/w) coated on Chromosorb W (AW, 45-60 mesh) by saturating the carrier gas (helium) with water vapour (Lindstrom et al., 1990). 

To recognize a chiral ammonium guest, binaphthyl hinge crowns were designed and proved the enantiomeric separation of protonated amino acid ester racemates [21]. A series of chiral azophenol acerands incorporating one or two optically active hydrobenzoin unit, 51-58, has been synthesized to study the title theme, enantiomer selective coloration with chiral amines. 

TABLE 2. Effectiveness of enantiomeric separations for racemates (a)-(f) using carbamate-functionalized polysaccharides entries lA, IB, and IIB described in Table 1 with hexane/2-propanol, 90 10, v/v, as the mobile phase at a flow rate of 0.5 ml/min at 25 C. 

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