Indirect Enantiomer Separation on a Preparative Scale

The separation of derivatized enantiomers after a reaction with a CDA opens an interesting route to direct enantiomer separation for preparative separations. If a method for mild cleavage of the diastereomers can be found, which does not lead to racemization, the use of expensive CSPs can be avoided. 

Enantiomer Separations Under Supercritical Fluid Chromatc raphic (SFC) Conditions 

Above a critical temperature and a critical pressure, so-called supercritical fluids show physical properties which position them between liquids and gases. Like gases, they are easily compressible, and properties such as density and viscosity can be modified by pressure and temperature changes. Below the critical temperature and at a pressure above the critical value, the fluid is transformed into a liquid that exhibits a low viscosity and high diffusion rates. Above the critical temperature and at a pressure below the critical value, the fluid turns into a gas [45]. 

For enantiomer separations, CO2 is most often used as fluid, since it is relatively cheap and non-toxic. The polarity of super- and sub-critical CO2 is equivalent to that of the lower alkanes and can be increased by adding modifiers (e.g., lower alcohols). In comparison to HPLC, SFC allows for higher plate counts and an improved resolution. Due to the lower viscosity, a smaller pressure drop is realized over the column, which allows the use of longer columns for analytical and preparative purposes. 

Very often, analysis times are shortened by using SFC. CSPs compatible with SFC are cellulose and amylose derivatives, brush-type CSPs, as well as macrocyclic phases. The selectivity of the CSPs is in many cases similar to that found on these phases in the normal-phase mode. 

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