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Prediction of the efficiency of diastereoisomer separation on the basis of the behaviour of enantiomeric mixtures

The driving force of homo- and heterochiral complex formation in mixtures of chiral compounds is, probably, the effort of the system to separate the most symmetric associates from the less symmetric ones. A possible way to achieve separation of these associates is distribution between two phases. Therefore, during the separation of (a certain part) diastereoisomers similar trends can be observed as in the course of the distribution of enantiomeric mixtures between two phases, although in the first case a third chiral compound (namely the resolving agent) is present. Of course in this case the pursuit of symmetry is not so obvious as in case of enantiomeric mixtures. It should be noted that the outcome may thus be modified by the intervention of kinetic control. One can conclude that the structure of chiral compounds encodes the result of the (optical) resolution.

Selecting Resolving Agents with Respect to Their Eutectic Compositions.

In order to develop a resolution procedure for a given racemic compound, the first and the most important step is finding the most suitable resolving agent. We studied 18 individual resolutions that were carried out with resolving agents having high eutectic composition. We found that very high enantiomeric excess values were obtained in all cases. We assume that the eutectic composition of a given resolving agent is one of the most important properties that should always be considered during the search for the most efficient resolving agent.

The pH-dependency of diastereomeric salt resolutions with amphoteric resolving agents

We have analysed the role of pH in the diastereomeric resolution of racemic mandelic acid with (S)-phenylalanine and (R)-3-(aminomethyl)-5-methylhexanoic acid [(R)-Pregabalin] enantiomers. The adjusted pH had an effect on the optical purity and yield of the mandelic acid enantiomeric mixtures isolated from the diastereomeric salts. We showed that the pKa of the carboxyl group of the amphoteric resolving agents should be considered during the pH optimisation of diastereomeric salt resolutions.

An aspect of selecting resolving agents: The role of differences in molecule length in diastereomeric salt resolutions

ABSTRACT In the course of 49 individual experiments of diastereomeric salt resolution we have examined the effect of the difference between the racemic and resolving agent molecule lengths on the resolution. We concluded that using resolving agents with the molecule length differing by 3 to 6 from the racemic molecule produces the best result.