Preparation enantioseparation

A selection of the most successful CSPs, chiral particles and chiral additive techniques used for analytical and preparative enantioseparation by LC is discussed in the following sections with respect to molecular recognition and experimental application. As additional sources of background information recent books and review articles2-16, which contain numerous relevant references and examine the most important aspects of the field of liquid chromatographic enantioseparation, should be consulted. 

Schulte, M. and Strube, J, (2001) Preparative enantioseparation by simulated moving bed chromatography. J. Chromatogr. A 906, 399-416. 

Advances in preparative enantioseparation by simulated moving bed (SMB) chromatography have occurred in the last 10 years. SMB was invented in the 1960s and was used by the petrochemical and sugar industries. Now with the improvements in stationary phases and hardware it is an option for the large-scale preparation of enantiomerically pure material. The majority of the latest published data are using either amylose- or cellulose-based phases because of their selectivity. There are now examples in the literature of the commercial separation on the multi-ton scale.8... 

Figure 21-4. Preparative enantioseparation of a morphanthridine analogue on an analytical Chiralpak-AD column (250-cm x 4.6-mm i.d.). Mobile phase Hexane/2-propanol = 85/15 (V/V), 0.5mL/min temperature 40°C, UV detection 290 nm, injection amount 100mg/250 xL hexane/2-propanol = 1/1 (V/V). (Reprint from reference 33, with permission.)...

TABLE 21-2. Calculated Production Scenarios for a Preparative Enantioseparation of a Morphanthridine Analogue on Chiralpak-AD... 

In this chapter we will focus on the moleciilcir recognition niechanisms of the diverse chiral SOs and CSPs in combination with their spectra of applicability, but also aspects concerning the separation systems as well as on issues that are of interest for practical applications. This will include a discussion of structure resolution relationships as support for the selection of certain CSPs for a given separation problem, operation modes and mobile phase composition, stability, the ability to reverse the elution order to elute each of the enantiomers as the first peak, and loadability which is of primary importance for preparative enantioseparations. 

Another marked disadvantage should be mentioned. As a consequence of the macromolecular nature of the selector, its molar loading on the support material is quite low. Since the number of binding sites per protein molecule is also limited (in contrast to polysaccharide and other polymeric CSPs consisting of the same repetitive sub-selector units), these CSPs have a low loadability [203]. This greatly restricts their use for preparative enantioseparations. 

The early systematic preparative enantioseparations of drugs performed on cross-linked chiral polyacrylamides in low-pressure LC mode clearly showed that even this non-opti-mal technique, from the viewpoints of performance and costs, may be useful for comparative biomedical studies of enantiomers of chiral drugs. 

Table 6. Selected examples of preparative enantioseparation of chiral drugs, drug candidates and drug intermediates using closed-loop recycling chromatography (CLRC)...

Some examples of preparative enantioseparation of chiral drugs are summarized in Table 9. Overall, SMB chromatography is a powerful tool for the production of enantiomerically pure compounds on a large scale within a short phase of development. The availability of software which allows scaling-up of an analytical enantioseparation to SMB technology is a crucial advantage. The characteristics of SMB chromatography are such as to provide pure... 

Rubio N, Minguillon C. Preparative enantioseparation of ( )-iV-(3,4-cis-3-decyl-l,2,3,4-tetrahydrophenanthren4-yl)-3,5-dinitrobenzamide by centrifugal partition chromatography. J. Chromatogr. A 2010 1217 1183-1190. 

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