Coupled Continuous Chromatography and Racemization Processes for the Production of Pure Enantiomers

Abstract

Combining an enantioseparation by continuous chromatography with the racemization of the undesired enantiomer in a recycle is a promising approach. Two different cases were considered: limited conversion of the reaction with moderate product purity requirements and high conversion with high product purity requirements. For the first case, a simple plantwide control strategy is presented, manipulating the solvent removal in front of the racemization reactor. It is shown that the various disturbances can be compensated with this strategy without performing the more complex readjustment of the chromatographic unit. Further, it is shown that this strategy is likely to fail in the second scenario and that readjustment of the chromatographic unit is required for a successful control strategy.

Integration of simulated moving bed chromatography and enzymatic racemization for the production of single enantiomers

“…In this work the experimental implementation of an integrated process for the production of single amino acid enantiomers from a racemate, employing continuous chromatography and biocatalysis, is presented for the first time. We demonstrate that this process can be operated in stable fashion for at least over 30 h despite i) highly non-linear adsorption isotherms, ii) the existence of a memory effect in the adsorption behavior of the CSP, and iii) the lack of sophisticated online control mechanisms that have been proposed for similar process combinations previously (Amanullah and Mazzotti, 2006;Swernath et al, 2014). The experimental proof of concept run was designed employing the traditional complete separation criterion for the SMB, meaning that both outlet purities should be nearly absolute.…”

“…In consequence, the SMB is challenged with a dynamic change in feed concentration which might require adaptation of SMB operating points during operation in order to ensure constant product purity. A recent work shows that product purities in a similar integrated process can be controlled by adjusting the retentate flow rate (Swernath et al, 2014): a similar approach can be envisioned for the integrated process concept presented in this work by reducing the feed flow rate.…”

Robustness of steady state recycling chromatography with an integrated solvent removal unit

“…For example, it has been recently demonstrated that robustness of hybrid process concepts where SMB chromatography is coupled with crystallization and solvent removal [9] or chemical reaction and solvent removal [17] can be improved by manipulating the solvent removal rate. There is thus an obvious need to understand how different operating parameters of coupled units interact with each other.…”

“…Many potential chromatography-based hybrid concepts have been proposed such as coupling of chromatography with crystallization [1][2][3][4][5][6][7][8][9], chemical reactions [10][11][12][13][14][15][16][17], partial solvent removal [18][19][20][21][22], or combinations of them [23,24].…”

Assessment of process configurations to combine enantioselective chromatography with enzymatic racemization

“…The process configurations investigated had different degrees of integration and complexity. Coupled systems were studied theoretically (von Langermann et al 2012;Nimmig and Kaspereit 2013;Swernath et al 2014) and were implemented experimentally for the production of D-Psicose (Wagner et al 2011). Additionally, a combination of chromatographic SMB separation and enzymatic racemization was used by Fuereder et al (2016) for the production of pure methionine enantiomers.…”