Traditional methods of production of enantiopure compounds include separation of racemates by crystallisation of diastereomeric salts, enzymatic resolution and increasingly also asymmetric catalysis. All these methods have certain advantages and may well b e the cheapest method for a particular chiral compound. However, in all cases the selection and optimisation of the method may take considerable development for each separate case and is still very much guided by a trial-and-error approach. An alternative approach to those described above for the separation of racemates, relies on the ability of chiral host compounds to discriminate between the two enantiomers of a racemate, thus allowing the physical separation of the enantiomers.
We plan to adopt a very promising method, namely the enantiomeric separation of racemic mixtures by extraction involving the selective coordination of one enantiomer to a hydrophobic chiral metal complex in the organic phase and the extraction of the uncomplexed enantiomer in the aqueous phase. The main objective of this project is the design and synthesis of chiral metal complexes for the enantioselective separation of racemic mixtures of entire classes of compounds (e.g. carboxylic acids, amino acid derivatives, hydroxy acids, but also amine derivatives) by extraction. Libraries of chiral ligands (ca. 100-125 compounds) will be synthesized in a parallel format, starting from a variety of chiral diamino or aminoalcohol scaffolds, and other chiral reagents (beta-aminosulfonyl chlori des, Boc-amino acids) as well as salicyl aldehydes.
Purification by chromatography of the intermediates and of the final products will be avoided by using solid-phase scavenger resins. The chiral complexes with transitions metals will then be synthesized and the selectors will be used in the enantioselective extraction of a variety of racemic substrates. In addition, the factors influencing the extraction and re-extraction enantioselectivity will be examined.
Fields of science
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