Stereoisomer separation

FIGURE 1.32 Stereoisomer separations of chrysanthemic acid (a) and fenvaleric acid (b) employing an 0-9-(tert-bntylcarbamoyl)qninine-based CSP in the polar-organic mode (a) and an 0-9-(2,6-diisopropylphenylcarbamoyl)quinine based CSP (b). Experimental conditions Column dimensions, 150 mm x 4mmID eluents(a)0.06%aceticacidin acetonitrile-methanol (95 5 v/v) (b) acetonitrile-0.3 M ammoninm acetate buffer (90 10 v/v) (pHa 6.0) flow rate, 0.65 mLmin temperature, 25°C detection, UV at 230 nm. (Reproduced from W. Bicker et al., J. Chromatogr. A, 1035 37 (2004). With permission.)... 

Scriba, G. K. E. (2006). Recent advances in peptide and peptidomimetic stereoisomer separation by capillary electromigration techniques. Electrophoresis 11, 222-230. 

R. Souter, Stereoisomer separations by gas chromatography. In Chromatographic Separations of Stereoisomers, CRC Press, Boca Raton, FL, pp. 11-85. 

Fluvoxamine (primary amine) Hypersil ODS, Spherisorb ODS-1, 3 pm Acetonitrile-phosphate buffer, pH 7.0 (60 40), 6 mM hexylamine 330 mm x 100 pm i.d. 250 mm packed length, 80 stereoisomer separation... 

Some of the enantiometric compounds separated by LC on a (3-cy-clodextrin column only 10 cm long are listed in Table 4,42 and a large number of drug stereoisomer separations have been summarized re-... 

The syntheses of sphingosines just described have a substantial advantage in comparison with those previously reported, because carbohydrates offer a variety of starting materials having known absolute configuration and, therefore, the necessity of stereoisomer separation does not arise. 

Conformational isomerism, as already defined (Section 3.b), is a property of stereoisomers separated by a low barrier of energy. The separation of isomers at room temperature requires half-lives of several hours, which correspond approximately to a free energy of activation of AG > 20 kcal/mol [56]. An operational and convenient definition of conformational isomerism is thus to consider as conformers those stereoisomers which are not physically separable under ordinary conditions, in other words, which are separated by an energy barrier lower than 20 kcal/mol. Such a definition is further useful in that it sets no conditions as to the chemical process by which conformer interconversion occurs while bond rotation is the most frequently encountered interconversion process, inversion processes are also important. 

The work in Adelaide then dealt with terpenes, mostly isolated from Australian plants. Mills worked on the synthesis of terpene analogs, and soon found that the cyclohexane system offered interesting stereochemical problems. He was also dismayed by the difficulty, in those days (before the rise of chromatography), of separating dia-stereoisomers. Separation and characterization of the 3-methylcyclo-hexanols presented his first problem, and similar compounds followed. For this research, he was awarded in 1947 the Rennie Memorial Medal, an annual award of the Royal Australian Chemical Institute for the best research carried out in Australia by a chemist under the age of 36. 

Despite the long recognition of chirality in POPs, it has only been fairly recently that studies of chiral POPs have been possible, after the introduction of analytical technology for stereoisomer separation by enantioselective gas chromatography (GC), high performance liquid... 

Multilayered Paracyclophane The three-layer paracylophane 33 was synthesized and the two stereoisomers separated. The question facing Kobayashi and colleagues was is the (-l-)-isomer of R or 5 stereochemistry Comparison of the computed and experimental ORs resolved the issue. 

Growth rate kinetics for most of the stereoisomer resolution processes run at Merck have been essentially first-order with respect to supersaturation, although there have been exceptions (see Chapter 11). For one of the stereoisomer separation systems, the (first-order) growth rate constant was measured for both the stirred tank (CSTR) and fluidized bed flow systems, with and without a nucleation suppressant. The data are shown in Table 7-5. 

Apphcations in analytical, biotechnological, environmental, and stereoisomer separations are reviewed. A few pilot-scale and industrial applications of the SLM processes are described. 

Another important problem is the enantiopurity of chiral pharmaceuticals and many other compounds with biological activity. Therefore, there is a gi eat interest in developing methods that can help in stereoisomer separation and improve the stereoselectivity of separation methods. In this case, a specific chiral environment should be created to ensure enantioselectivity of separation. 

Figure 6.15 Schematic hollow-fiber contained liquid membrane permeator (HFCLMP) used for stereoisomers separation. From Ref. [93] with permission.

The second important observation on stereoisomer separation also involved ammonium sodium tartrate. Thirty-four years after Pasteur s observation, Jungfleisch (1882) observed that carefully introducing crystals of the individual isomers into different areas of a supersaturated solution of ammonium sodium tartrate resulted in the growth of isomerically pure crystals. These two observations form the basis for most industrial scale crystallizations for the purification of enantiomers or diastereoi-somers. However, it is more common for a solute to crystallize with the thermodynamically stable crystal form being a compound of the two isomers. This is typically denoted as a racemic compound. Secor (1963) made the first systematic review of optical isomer separation by crystallization, based upon phase behavior. Collet, Brienne, and Jacques (1980) applied systematic thermodynamics to the phase behavior, and developed straightforward methods for correlating the solubilities of isomers. 

Gedicke, K., Kaspereit, M., Beckmann, W., Budde, U Lorenz, H and Seidel-Morgenstern, A. (2007) Conceptual design and feasibility study of combining continuous chromatography and crystallisation for stereoisomer separations. Chem. Eng. Res. Des., 85, 928-936. 

Normal-phase column liquid chromatography using unmodified silica gels has been used for the purification of both natural and synthetic compounds. It is a powerful tool for stereoisomer separations. The instability of unmodified silica gel means that its use for quantitative analysis in column liquid chromatography is avoided because of poor reproducibility. Normal-phase separation has, however, been performed using thin-layer liquid... 

Stereoisomers separable by crystallization. Diphenyl sulfoxide main product. 

Figure 4 Simultaneous chiral separation of the isomeric tripeptides Gly-a-Asp-PheNH2 and Gly- -Asp-PheNHa. Experimental conditions 40/47cm polyacrylamide-coated capillary, 50 im, 50 mmol I sodium phosphate buffer, pH 5.25, 60mgmr car-boxymethyl- -cyclodextrin, -20 kV, UV detection at 215 nm. (Reprinted with permission from Sabah S and Scriba GKE (1998) Electrophoretic stereoisomer separation of aspartyl dipeptides and tripeptides in untreated fused-siiica and polyacrylamide-coated capillaries using charged cyclodextrins. Journal of Chromatography A 822 137-145 Elsevier.)...

The d-stereoisomer of the A-methylconilne was separated from coniine, from which it was distinguished by its rotary power, in a plant extract provided by the Merck factory, and the 1-stereoisomer separated as the hydrobromide, again from coniine, in a plant extract also from the Merck factory [15]. 

Sabah S, Scriba G (1998) Electrophoretic stereoisomer separation of aspartyl dipeptides and tripeptides in untreated fused-silica and polyacrylamide-coated capillaries using charged cyclodextrins. J Chromatogr A 822 137-145... 

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