Development of a supported liquid membrane process for separating enantiomers of N-protected amino acid derivatives

A continuous supported liquid membrane (SLM) process was developed to separate enantiomers of racemic N-protected amino acid derivatives using the advantages provided by highly selective carbamoylised quinine and quinidine derivatives when used as a carrier. The special characteristic of this process is that both enantiomers can be separated with degree of purity of 99% and in large quantities (in grams). The prototype of a SLM plant consisted basically of two hollow fibre membrane modules with 250 individual polysulfone hollow fibres, a total membrane surface of 0.1 m2 and a molecular weight cut-off of 30 kD. The liquid membrane in the pores consisted of adamantyl-carbamoyl-11-octadecylthioether-quinine (module 1) and -quinidine (module 2), which was dissolved in 1-decanole/pentadecane. The enantioselective separation process operates on a continuous basis in aqueous phases. The amino acid derivatives DNB-d,l-leucine, DNZ-Tle, DNZ-ABA and DNZ-β-Phe based on the racemate could be separated in the SLM plant with a degree of selectivity between 2 and 4. Crystallisation on the membrane, which is occasionally observed was prevented by adding a 5 vol.% polysiloxane-bonded quinine/quinidine polymer to the carrier. Furthermore, improved resistance to mechanical influences (leaching) could be guaranteed. The model substance DNB-d,l-leucine was used to test the process. After five separation steps, a 99% d-enantiomer and a 99% l-enantiomer could be produced at a transmembrane flux of more than 20 mmol/m2h. It could be shown that SLM technology can offer a high level of productivity and flexibility compared to analogous industrial-scale chiral technologies