Enantiomer of chiral drugs

E. R. Francotte and R Richeit, Applications of simulated moving-bed cliromatography to the separation of the enantiomers of chiral drugs , ]. Chromatogr. 769 101-107 (1997). 

Erancotte E., Richert P. (1997) Applications of Simulated Moving-Bed Chromatography to the Separation of the Enantiomers of Chiral Drugs, J. Chrotnatogr. A 769 101-107. 

Biologically active compounds usually have at least one asymmetric centre and dramatic differences in the activities of different enantiomers of chiral drugs are commonly observed (see Box 23.6). Whereas one enantiomer may be an effective therapeutic drug, the other may be inactive or highly toxic as was the case with thalidomide. Asymmetric synthesis is therefore an active field of research. 

Due to the low volatility and thermostability, enantiomers of chiral drugs are basically resolved as their more volatile and stable derivatives obtained by the interaction of parent drugs with isocyanates, trifluoracetic acid, phosgene, etc. Sometimes, derivatization can be performed not only in order to meet the volatility and stability requirements but also in order to improve the chemo- and enantioselectivity of separation. Certainly, a derivatization with a chiral derivatizing reagent and the separation of the covalent diastereomeric compounds on an achiral CSP is also possible, but is essentially not used. 

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. 

That the resolution of the enantiomers of chiral drugs should be considered as a topic in its own right in a treatise on pharmaceutical analysis should come as no surprise. The importance of chirality in many fields of natural and applied science is well established [1]. In pharmaceutical analysis, this topic which commands its own nomenclature (Table 3.1) is especially important, as is apparent from the proportion of drugs on the market that are chiral (Table 3.2). 

Polymorphism and pseudopolymorphism are known among chiral drugs. Whereas the enantiomers of chiral drugs may display ordinary polymorphism, the racemic species show a special type of polymorphism, namely conversion between the different types of racemate. For example, racemic sodium ibuprofen exhibits three polymorphs, the stable polymorph at room temperature being the conglomerate while the other two polymorphs, which are racemic compounds, are obtained by rapidly cooling the melt of the conglomerate [21]. 

Cellulose Triacetate. Cellulose triacetate (triethylcellulose) can interact stereoselectively with enantiomers of chiral drugs [48-50]. It has regions of crystallinity, which allow for enantioselective inclusion of drugs (solutes), especially those having substituent-free phenyl groups. However, it loses its enantioselectivity when solubilized and reprecipitated owing to the breakdown of the crystalline structure. 

Head groups of ceramides contain multiple hydroxyl groups with a well-defined stereochemistry, so that stereospecific interactions between ceramides and enantiomers of a chiral drug may cause enantioselective permeation. In addition, differential binding of enantiomers of chiral drugs... 

Table 3 Unbound Fractions of Enantiomers of Chiral Drugs in Human Plasma for Drugs Discussed in this Chapter ... 

Biologically active compounds usually have at least one asymmetric centre and dramatic differences in the activities of different enantiomers of chiral drugs are commonly... 

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