Assessment of process configurations to combine enantioselective chromatography with enzymatic racemization

Abstract

Enantioselective chromatography is nowadays a reliable tool for single enantiomer production from a racemate. The recovery of the distomer by racemization and recycling is a promising method to tackle the 50% yield constraint and to increase the productivity. In this paper three process configurations are compared. The production of enantiopure mandelic acid and methionine enantiomers exploiting different enzymes for racemization are evaluated as part of different chromatographic process configurations. First, the benefits of conventional simulated moving bed (SMB) chromatography in contrast to a single column batch separation unit are assessed in integrated configurations. Then, a concept of coupling the racemization with a simpler three-zone SMB unit, where one regeneration zone is removed, is evaluated.

Characterization of an Immobilized Amino Acid Racemase for Potential Application in Enantioselective Chromatographic Resolution Processes

“…In the scenario considered for illustration, the production of D-Met with a purity of 99% is evaluated, analysing the setup shown in Figure 10. It is known that, in the chromatographic step, 20 g/L DL-Met could be separated with an ee D = 99% in the product stream and an ee L = 90% in the by-product stream [8,25], which is ready to be recycled. The recycling stream can be first concentrated in a distillation column to lower the alcohol fraction to ≤5 vol% while increasing the total concentration again to c tot 20 g/L DL-Met.…”

“…This investment of 1% dedicated additional mass can double the overall process yield and has the potential to improve the productivity of providing the pure target enantiomer. Further, not discussed here, potential improvement can be achieved if the purity constraints of the chromatographic step are relaxed [8,25].…”

“…Astec Chirobiotic T (Sigma-Aldrich, St. Louis, MO, USA) is based on the macrocyclic glycopeptide Teicoplanin. This CSP has been shown to resolve many pairs of enantiomers under conditions that are compatible for enzymatic reactions [25]. Chirobiotic T columns can separate racemic mixtures of enantiomers of numerous chiral molecules, including enantiomers of amino acids, in water-based eluents.…”

Forschungsarbeiten am Institut für Verfahrenstechnik der Otto‐von‐Guericke‐Universität Magdeburg

“…Kopplung von kontinuierlicher SMB‐Chromatographie mit enzymatischer Racemisierung zur verlustfreien Gewinnung von reinen Enantiomeren aus racemischen Mischungen 9.…”

“…Abb. 4 zeigt eine leistungsstarke, auf dem Prinzip der Simulated Moving Bed (SMB)‐Chromatographie basierende integrierte Prozessvariante 9.…”