Preparing Pure Enantiomers

It is important to note, however, that economic constraints may often make it too expensive to replace an existing technology that consists of racemate preparation followed by separation, by a process based on chiral synthesis. 

Several methods of isolating an enantiomer in its pure form or of synthesizing it directly from a substrate have been in use. A classification of these is given in Table 9.3. 

Serial no. Name of compound Absolute configuration Biological effect 

There are essentially three important variations of this traditional method, as described next. 

For the drug diltiazem, using (S)-a-methylbenzylamine as the resolving agent  

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As these adduct isomers may easily be separated by chromatography one can again make use of the thermal retro-process to prepare pure enantiomers. 

There are three ways to prepare pure enantiomers ... 

Since the first separation of enantiomers by SMB chromatography, described in 1992 [95], the technique has been shown to be a perfect alternative for preparative chiral resolutions [10, 21, 96, 97]. Although the initial investment in the instrumentation is quite high - and often prohibitive for small companies - the savings in solvent consumption and human power, as well as the increase in productivity, result in reduced production costs [21, 94, 98]. Therefore, the technique would be specially suitable when large-scale productions (>100 g) of pure enantiomers are needed. Despite the fact that SMB can produce enantiomers at very high enantiomeric excesses, it is sometimes convenient to couple it with another separation... 

Enantiomeric separations have become increasingly important, especially in the pharmaceutical and agricultural industries as optical isomers often possess different biological properties. The analysis and preparation of a pure enantiomer usually involves its resolution from the antipode. Among all the chiral separation techniques, HPLC has proven to be the most convenient, reproducible and widely applicable method. Most of the HPLC methods employ a chiral selector as the chiral stationary phase (CSP). 

For preparative or semipreparative-scale enantiomer separations, the enantiose-lectivity and column saturation capacity are the critical factors determining the throughput of pure enantiomer that can be achieved. The above-described MICSPs are stable, they can be reproducibly synthesized, and they exhibit high selectivities - all of which are attractive features for such applications. However, most MICSPs have only moderate saturation capacities, and isocratic elution leads to excessive peak tailing which precludes many preparative applications. Nevertheless, with the L-PA MICSP described above, mobile phases can be chosen leading to acceptable resolution, saturation capacities and relatively short elution times also in the isocratic mode (Fig. 6-6). 

Two methods are used in practice to obtain enantiomerically pure amino acids. One way is to resolve the racemic mixture into its pure enantiomers (Section 9.8). A more direct approach, however, is to use an enantioselective synthesis to prepare only the desired 5 enantiomer directly. As discussed in the Chapter 19 Focus Oil, the idea behind enantioselective synthesis is to find a chiral reaction catalyst that will temporarily hold a substrate molecule in an unsymmetrical environment. While in that chiral environment, the substrate may be more... 

Homochiral (5)- and (f )-l-(2-furyl)ethanols were prepared from 21 by lipase-catalyzed transesterification with vinyl acetate. The pure enantiomers are preciusors for the syntheas of L-and D-daunomycin <96TA907>. 

The preparation of enantiomerically pure drugs is one factor that makes enantioselective synthesis and the resolution of racemic drugs (separation into pure enantiomers) active areas of research today. 

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