Efficiency enantioseparation

Very efficient enantioseparation of racemic DNB-leucine 23 exploiting an extraction with a mechanistically designed quinine 1-adamantylcarbamate 24 bearing a highly hydrophobic side arm has been reported by Lindner and coworkers. The most efficient extraction was achieved with aqueous ammonium acetate buffer/dodecane solvent system. After back-extraction of the organic phase with 1 M H3PO4 solution, the preferentially complexed S-enantiomer of 23... 

Ikai T, Yamamoto C, Kamigaito M, Okamoto Y (2008) Organic-inorganic hybrid materials for efficient enantioseparation using cellulose 3,5-dimethylphenylcarbamate and tetraethyl orthosilicate. Chem Asian J 3 1494—1499... 

Efficient methods of enantioseparation are always required to control the enantiomeric purity, or to separate the target molecule or one of its chemical precursors (obtained from conventional synthetic procedures), or for monitoring the completion of enantioselective reaction process (since the production of single enantiomer is a real difficult task). 

Sztojkov-lvanov, A. et al., Comparison of separation efficiency of macrocyclic glycopeptide-based chiral stationary phases for the LC enantioseparation of fi-amino acids, Chromatographia, 64, 89, 2006. 

Cyclodextrins have significantly contributed to the development of enantioseparations in CE, where they represent the most widely used chiral selectors. On the other hand, due to its inherently high separation efficiency and diverse technical advantages, CE has contributed enormously to the better understanding of affinity interactions between CDs and chiral analytes. The following text summarizes the recent developments in this field (3-60). 

The use of polysaccharide-based CSPs instead of protein-based CSPs often increases the peak efficiency and facilifafes faster separafions. Papini ef al. [159] recently developed a method for the enantioseparation of lorazepam and on a Chiralpak OD-R column and an enzymatic hydrolysis was used to determine the amount of the glucoronide metabolite of lorazepam present. The separation was performed in 7 min with an LOQ of 1 and 10 ng/mL for lorazepam in plasma and urine, respectively. Another relatively fast separation for chiral analysis was published by Lausecker and Eischer [188]. They developed a method for determination of the drug candidate R483 within... 

The analysis time for chiral HPLC separations will probably remain relatively long until CSPs with higher efficiency than the present ones become available. But monolithic columns, columns with a smaller particle size (i.e., UPLC ), and miniaturized systems would increase the efficiency and speed up the enantioseparation of existing types of CSPs. 

An efficient and simple kinetic resolution of the racemic Betti base 387 was achieved via its reaction with acetone in the presence of L-(- -)-tartaric acid. When a suspension of racemic 387 in acetone was treated with L-(- -)-tartaric acid, the (A)-enantiomer formed a crystalline L-tartrate salt 389 this was filtered off, and the (iJ)-enantiomer could be isolated as a naphth[l,2-< ]oxazine derivative 388 from the filtrate (Equation 41). Both enantiomers were obtained in excellent yields and ee s. The enantioseparation is presumed to take place via a kinetically controlled N,0-deketalization of the (3)-naphth[l,2-< ]oxazine derivative <2005JOC8617>. An improved method for the enantioseparation of 387 was developed by the reaction of the ring-chain tautomeric l,3-diphenyl-3,4-dihydro-2//-naphth[2,l-< ][l,3]oxazine (41 X, Y = H) and L-(-f)-tartaric acid, yielding the crystalline 389 in 85% yield <2007SL488>. 

Brush or Pirkle-type CSPs show promise in the enantioseparation of many classes of compounds, and also have shown to exhibit the high efficiencies expected in CEC separations. The high efficiency of enantioseparations of these CSPs is thought to be due to more favorable mass transfer kinetics between the analytes and these CSPs. Cavender et al. [144] used these CSPs bonded to silica particles to separate 10 chirally active compounds. They used (S)-Naproxen-derived CSP as well as the more widely used (3R, 4S)-Whelk-0. They found that while the (S)-Naproxen-derived CSP gave rise to more reproducible EOF, (3R,4S)-Whelk-0 gave more efficient separations. The reproducibility of the... 

Synergistic effects in terms of efficiency of CE enantioseparation have been observed when a second (not necessarily chiral) selector is added in the same buffer system. It has been demonstrated that a combination of 18-crown-6 and )-cyclodextrin can achieve or enhance enantioselective separations of nonpolar amines, which are rarely observed with cyclodextrins alone <1997JCH(781)129, 1997JCH(695)157>. The formation of a ternary sandwich complex (dual complex) is postulated to be responsible for such a beneficial effect. 

Co(acac)3 is frequently used as a probe for enantioseparation efficiency of col-umns " . A monolytic capillary silica gel column was functionalized with methacrylate residues in two steps, as shown in equation and then it was impregnated with cellulose or amylose (51a, b) which was modified so that 30% of the R groups were the methacrylate group 52 and the rest was identical to R (53). For further stability of the column, the polymeric modifier was immobilized on the silica gel by in situ copolymerization with an olefinic monomer such as 2,3-dimethylbutadiene. Only the column containing cellulose modified as in 51a was able to separate the Co(acac)3 racemic mixture, whereas neither cellulose nor amylose modified as in 51b did, although they were successful in resolving other racemic mixtures ° °. ... 

The efficiency of chiral stationary phase (CSP) is crucial in chromatographic technique. Recently, a new p-cyclodextrin phenyl isocyanate bonded chiral stationary phase (CSP) was developed. This CSP is quite stable and can be used in most of HPLC solvents. Many drug enantiomers that do not have enantioseparation effect on native P-cyclodextrin column in reversed phase were separated very well on this new CSP. 

The use of a convective macroporous polymer as an alternative support material instead of silica for the preparation of protein-based CSPs has successfully been demonstrated by Hofstetter et al. [221]. Enantioseparation was performed using a polymeric flow-through-type chromatographic support (POROS-EP, 20 pm polymer particles with epoxy functionalities) and covalently bound BSA as chiral SO. Using flow rates of up to 10 ml/min, rapid enantiomer separation of acidic compounds, including a variety of amino acid derivatives and drugs, could be achieved within a few minutes at medium efficiencies, typical for protein chiral stationary phases (Fig. 9.13). 

SAs, e.g. A -acetyl phenylalanine, have been resolved with purely aqueous buffered mobile phases however, with lower efficiency than under aqueous-organic conditions. Most enantioseparations investigated so far are enthalpically driven as exemplified in Fig. 9.34d) for DNS-valine. 

For a quite long period of time, chiral ligand-exchange chromatography (CLEC) has been the standard method for the enantioseparation of free amino acids. Meanwhile, other methods became available for these target molecules, such as teicoplanin or chiral crown-ether-based CSPs. However, for the enantioseparation of aliphatic a-hydroxy carboxylic acids, it is still one of the most efficient methods. 

Because solutes have higher diffusion coefficients in super(sub)critical fluids than in liquids, the optimum linear velocity is shifted to higher values. Consequently, higher flow rates can be used leading to reduced analysis (separation) time without compromising efficiency. In addition, although the chiral discrimination ability of CSPs and enan-tioselectivity in SFC resemble usually those of non-aqueous LC, in some cases enantioseparations can be obtained in SFC which cannot be achieved in conventional LC. 

In addition to the pressure-driven liquid-phase enantioseparation techniques (LC and SFC), in recent years electrically driven separation methods have also become popular for analytical enantioseparations, primarily owing to the high efficiencies that can be achieved. 

Up till now the most universal and efficient chiral selectors used for GC enantioseparation have appeared to be cyclodextrins. 

The first separations of enantiomers in GC on cyclodextrin modified column were carried out by Sybilska et al. in 1983 [5], They applied a formamide solution of a-cyclodextrin as a stationary phase in the classical packed column. The column allowed an efficient separation of chiral monoterpenes - a- and P-pinenes into enantiomers. This system of using CDs in GC is characterised by obtaining high enantioselectivity factors, so enantioseparation is still possible for receiving not very efficient packed columns. Unfortunately, the columns appeared to be not very stable at higher temperatures. 

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