Preparation of enantiopure chemicals is still a hot topic in research although there is already a large chiral market. In principle two routes are possible: the synthetic route and isolation from natural sources, typically from plant biomass. Isolation from natural sources is an interesting route not only to obtain single chiral components, but also to prepare mixtures having certain bioactivities. Enantiomer separation by the synthetic route is performed typically either by chiral catalysis of a reaction with a prochiral substrate or by optical resolution of a racemate. Regardless which method is applied, in most of the cases only enantiomeric mixtures are produced in the first step. This is followed by a further purification process, most typically by several recrystallizations. These are time and solvent intensive steps, resulting in significant amounts of the expensive enantiomers or diastereomers dissolved in the solvent phase, while solvent residues are present in significant amounts in the solid phase. After achieving the enantiopure final product size reduction is also typically required before formulation, in the pharma industry at least. Antisolvent fractionation with supercritical carbon dioxide recently gained attention in the scientific literature. The possibility of further purifying either a mixture of the diastereomeric salts of a compound or an enantiomeric mixture can be investigated by recording the ee1 –ee0 or de1 – de0 diagrams of the compounds, where ee and de are enantiomeric and diastereomeric excess, respectively. Such diagrams are also useful in determining the limits of further purification, similarly to those observed in atmospheric resolutions. It must be noted, that antisolvent fractionation is based on fast oversaturation and immediate precipitation followed by an extraction step. It is worthwhile to systematically study when the kinetic effects, and when the thermodynamics of the system (represented by the melting point phase diagrams) are dominant. The process can be influenced strongly by the solubility of the components (the pure enantiomers and the racemic forms or the diastereomeric salts) in supercritical carbon dioxide.

The research is assumed to lead to a better understanding how the chemical equilibrium, the solubility of the compounds present and the kinetics of the process influence the efficiency of the enantiomeric/diastereomeric enhancement.

Most relevant publications: 

Márton Kőrösi, János Madarász, Tamás Sohajda, Edit Székely, Fast further purification of diastereomeric salts of a nonracemic acid by gas antisolvent fractionation, CHIRALITY: THE PHARMACOLOGICAL BIOLOGICAL AND CHEMICAL CONSEQUENCES OF MOLECULAR ASYMMETRY 29:(10) pp. 610-615. (2017)

Márton Kőrösi, János Madarász, Tamás Sohajda, Edit Székely, A fast, new method to enhance the enantiomeric purity of non-racemic mixtures: self-disproportionation of enantiomers in the gas antisolvent fractionation of chlorine-substituted mandelic acid derivatives, TETRAHEDRON-ASYMMETRY Paper TETASY 59695. (2017)

 

   
© BME, Research Group on Supercritical Fluids, 2015