Chiral stationary phases ethers

Among various types of chiral stationary phases, the host-guest type of chiral crown ether is able to separate most amino acids completely (58). 

Many times an analyte must be derivatized to improve detection. When this derivatization takes place is incredibly important, especially in regards to chiral separations. Papers cited in this chapter employ both precolumn and postcolumn derivatization. Since postcolumn derivatization takes place after the enantiomeric separation it does not change the way the analyte separates on the chiral stationary phase. This prevents the need for development of a new chiral separation method for the derivatized analyte. A chiral analyte that has been derivatized before the enantiomeric separation may not interact with the chiral stationary phase in the same manner as the underivatized analyte. This change in interactions can cause a decrease or increase in the enantioselectivity. A decrease in enantioselectivity can result when precolumn derivatization modifies the same functional groups that contribute to enantioselectivity. For example, chiral crown ethers can no longer separate amino acids that have a derivatized amine group because the protonated primary amine is... 

Racemic modifications may be resolved. There are very few examples of this approach having been employed successfully. The racemic cylic ether (RS)-36, which contains two CH2OCH2CO2H arms attached to the 3 and 3 positions on the axially chiral binaphthyl units, has been resolved (48-50, 93, 94) to optical purity in both its enantiomers by liquid-liquid chromatography using a chiral stationary phase of either (R)- or (S)-valine adsorbed on diatomaceous eaitii. Very recently, the optical resolution of crown ethers (/ S)-37 and (/ 5)-38, incorporating the elements of planar chirality in the form of a rron -doubly bridged ethylene unit, has been achieved (95) by HPLC on (+)-poly(triphenyl-methyl methacrylate). 

The mixture was extracted with diethyl ether (three times). The combined organic layers were washed with brine and dried over sodium sulfate. After concentration in vacuo, the residue was purified by silica gel flash column chromatography (hexane/ethyl acetate = 20/1-3/1) to give (5)-l (426.3 mg, 74%, 98% ee) as a colourless solid. The enantiomeric excess of (5)-l was determined by chiral stationary-phase HPLC analysis DAICEL CHIRALCEL OD-H, j-PrOH/hexane 1/4, flow rate l.OmLmin tR 14.0 min [(R)-isomer)] and 21.3 min [(5)-isomer), detection at 254 nm]. ... 

Chiral crown ethers based on IB-crown-6 I Fig. 4> can form inclusion complexes with ammonium ions and proionated primary amines. Immobilization of these chiral crown ethers on a chromatographic support provides a chiral stationary phase which can resolve most primary amino acids, amines and amino alcohols. However, the stereogenic center must be in fairly close proximity in the primary aininc lor successful chiral separalion. Significantly, ihe chiral crown ether phase is unique in that ii is one of the few liquid chromatographic chiral stationary phases that does not require the presence of an aromatic ring to achieve chiral separations. 

Crown Ether-Based Chiral Stationary Phases... 

In view of the importance of chiral resolution and the efficiency of liquid chromatographic methods, attempts are made to explain the art of chiral resolution by means of liquid chromatography. This book consists of an introduction followed by Chapters 2 to 8, which discuss resolution chiral stationary phases based on polysaccharides, cyclodextrins, macrocyclic glyco-peptide antibiotics, Pirkle types, proteins, ligand exchangers, and crown ethers. The applications of other miscellaneous types of CSP are covered in Chapter 9. However, the use of chiral mobile phase additives in the separation of enantiomers is discussed in Chapter 10. 

The most popular and commonly used chiral stationary phases (CSPs) are polysaccharides, cyclodextrins, macrocyclic glycopeptide antibiotics, Pirkle types, proteins, ligand exchangers, and crown ether based. The art of the chiral resolution on these CSPs has been discussed in detail in Chapters 2-8, respectively. Apart from these CSPs, the chiral resolutions of some racemic compounds have also been reported on other CSPs containing different chiral molecules and polymers. These other types of CSP are based on the use of chiral molecules such as alkaloids, amides, amines, acids, and synthetic polymers. These CSPs have proved to be very useful for the chiral resolutions due to some specific requirements. Moreover, the chiral resolution can be predicted on the CSPs obtained by the molecular imprinted techniques. The chiral resolution on these miscellaneous CSPs using liquid chromatography is discussed in this chapter. 

The chiral recognition mechanisms in NLC and NCE devices are similar to conventional liquid chromatography and capillary electrophoresis with chiral mobile phase additives. It is important to note here that, to date, no chiral stationary phase has been developed in microfluidic devices. As discussed above polysaccharides, cyclodextrins, macrocyclic glycopeptide antibiotics, proteins, crown ethers, ligand exchangers, and Pirkle s type molecules are the most commonly used chiral selectors. These compounds... 

Schurig, V., Biirkle, W., Hintzer, K, and Weber R. (1989a) Evaluation of nickel(II) bis[a-(heptafluorobutanoyl)-terpeneketonates] as chiral stationary phases for the enantiomer separation of alkyl-substituted cyclic ethers by complexation gas chromatography, J. Chromatogr. 475, 23-44. 

The thermodynamic and hydrogen-bond basicity of 1 have been reported by the group of Berthelot, Laurence and coworkers (04CJC1413). TB 1, TB 110 and another mixed crown ether TB have been reported in a communication dealing with a novel chiral stationary phase for HPLC (94JCS(CC)1811). 

Analytical Properties CSP (chiral stationary phase) 1 — separates some chiral binaphthyl derivatives when mixtures of hexane diethyl ether, dichloromethane, or dioxane are used as the mobile phase CSP 2 — separates compounds with carbamate or amide functions (mixtures of n-hexane and 2-propanol can be used as mobile phase) CSP 3 — separation of compounds separated by CSP 2, as well as separation of compounds with carbonyl or amide functions and some amino alcohols that have pharmaceutical relevance ((3-blockers)... 

To a stirred solution of ketone (1 mmol) and fluoride salt (0.02 mmol) in dry THF was added the silane (1.5 mmol). The mixture was stirred at r.t. until the reaction was complete (TLC-monitored). NaOH (5 mL of a 3 M solution) was added drop-wise. After stirring vigorously overnight, the solution was extracted with diethyl ether (3 x 15 mL). The combined organic extracts were washed with water, dried (MgS04), and evaporated in vacuo. The residue was purified by chromatography (Si02) or distillation if necessary. Enantiomeric excess was measured by chiral stationary phase GC-analysis (Chiraldex G-TA column). 

Owing to the different biological activity of D- and L-enantiomers of seleno-amino acids, the chiral separation of optical isomers has been undertaken in sele-nized yeast and in yeast-based commercial supplements. Both, chiral stationary phase (crown ether) and chiral derivatization prior to reversed-phase HPLC were used [16, 77, 78],... 

Chiral separations can be considered as a special subset of HPLC. The FDA suggests that for drugs developed as a single enantiomer, the stereoisomeric composition should be evaluated in terms of identity and purity [6]. The undesired enantiomer should be treated as a structurally related impurity, and its level should be assessed by an enantioselective means. The interpretation is that methods should be in place that resolve the drug substance from its enantiomer and should have the ability to quantitate the enantiomer at the 0.1% level. Chiral separations can be performed in reversed phase, normal phase, and polar organic phase modes. Chiral stationary phases (CSP) range from small bonded synthetic selectors to large biopolymers. The classes of CSP that are most commonly utilized in the pharmaceutical industry include Pirkle type, crown ether, protein, polysaccharide, and antibiotic phases [7]. 

M. H. Hyun, J. S. Jin, and W. Lee, Liquid chromatographic resolution of racemic amino acids and their derivatives on a new chiral stationary phase based on crown ether, / Chromatogr. 822 (1998), 155. 

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