Page 32 - Chiral Separation Techniques

1.3 Chromatographie Techniques 7

1.3.1.2 Flash Chromatography

Flash chromatography is widely employed for the purification of crude products
obtained by synthesis at a research laboratory scale (several grams) or isolated as
extracts from natural products or fermentations. The solid support is based on silica
gel, and the mobile phase is usually a mixture of a hydrocarbon, such as hexane or
heptane, with an organic modifier, e.g. ethyl acetate, driven by low pressure air.
(Recently the comparison of flash chromatography with countercurrent chromato-
graphy (CCC), a technique particularly adapted to preparative purposes, has been
studied for the separation of nonchiral compounds [90].)
With regard to the resolution of enantiomers, some applications can be found with
modified silica gel supports. Thus, a Pirkle-type CSP was used for the separation of
200 mg of a racemic benzodiazepinone [75]. Also tris-(3,5-dimethylphenyl)carba-
mate of cellulose coated on silica C [91, 92] was applied successfully to the reso-
18
lution of the enantiomers of 2-phenoxypropionic acid and to oxprenolol, alprenolol,
propranolol among other basic drugs. However, the low efficiency of this technique
and the relative high price of the CSPs limits its use to the resolution of milligram
range of sample.

1.3.1.3 Simulated Moving Bed (SMB)

The simulated moving bed (SMB) technology was patented in the early 1960s as a
binary continuous separation technique. It consists of a series of several columns
connected to each other head-to-tail, simulating an annular column. The eluent
source, the feed of mixture to process and the two collecting positions move along
this circle in such a way that mimics a relative countercurrent movement between the
mobile and the stationary phases. This makes compatible the continuous injection of
mixture to be purified, and the recovery of two different fractions with the chro-
matographic process [93]. The feature of being continuous was considered an advan-
tage in order to be included in a production chain, when related to other existing sep-
aration techniques that act mainly in a batch basis. Although the ability to obtain two
fractions from a mixture might be seen as a limitation, SMB found very important
applications in the petro-chemical and sugar industries [94]. However, it was not
until some decades later that such a binary technique was realized to be advanta-
geous and especially suited to the separation of enantiomeric mixtures.
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 instrumen-
tation 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 enan-
tiomeric excesses, it is sometimes convenient to couple it with another separation