Phenylalanine enantioseparation

Huang, D.S., Huang, K.L., Chen, S.P. et al. (2008) Rapid reaction-diffusion model for the enantioseparation of phenylalanine across hollow fiber supported liquid membrane. Separation Science and Technology, 43 (2), 259-272. 

Direct and indirect RP chromatographic methods were developed and compared in systematic examinations for the enantioseparation of several unnatural P-amino acids, including some 3-3-homo amino acids. Direct separation of underivatized analytes involved the use of commercially available TE and TAG CSPs [150], while indirect separation was based on precolumn derivatization with (15,25)-l,3-diacetoxy-l-(4-nitrophenyl)-2-propylisothiocyanate and (S)-A-(4-nitrophenoxycarbonyl)phenylalanine methoxyethyl ester. 

Peter, A. et al., Enantioseparation by HPLC of imino acids on macrocyclic glycopeptide stationary phases and as their (5)-N-(4-nitrophenoxycarbonyl)-phenylalanine methoxyethyl ester derivatives, Chromatographia, 56, S41, 2002. 

SAs, e.g. A -acetyl phenylalanine, have been resolved with purely aqueous buffered mobile phases however, with lower efficiency than under aqueous-organic conditions. Most enantioseparations investigated so far are enthalpically driven as exemplified in Fig. 9.34d) for DNS-valine. 

MeOH was the best solvent for the first enantioseparation to give the (S) (.S ) H2O salt with 93% diastereomeric purity (30% yield). An equimolar mixture of (R)-enriched (40%) a-amino-e-caprolactam and N-tosyl-(S)-phenylalanine, which was recovered upon concentrating the mother hquor, was crystallized from 89% aqueous 2-PrOH/H2O (89/11) to give the (P)-(S) salt with a high resolution efficiency (41% yield, 93% diastereomeric purity). The processes could be repeated with high reproducibility (the first enantioseparation 29-31% yield, 91-93% diastereomeric purity the second enantioseparation 41-42% yield, 91-94% diastereomeric purity). The diastereomeric purity of the crude salts could be easily improved by recrystallization once from MeOH and 2-PrOH/H2O (89/11), respectively, to afford fhe pure salts with a diastereomeric purity of more than 99%. Treatment of the salts with 35% HCl in EtOH, followed by recrystallization gave a-amino-e-caprolactam-HCl with enantiomeric excess of more than 99.9%. 

Examples of Enantioseparations in the Pharmaceutical Industry 149 Table 5.13 Enantioseparation of la-amino- -caprolactam with N-tosyl-t-phenylalanine. 

Covalent immobilization of (photo) initiator groups on the support surface (see Scheme 4c) had been done on silica particles using a silanization with a conjugate of an azo-initiator [79,80]. MIP functionalization with L-phenylalanine anilide as template and MAA/EDMA along with UV-initiation [79] was feasible without significant polymerization in the bulk of the reaction mixture, and the synthesized composite materials were superior compared to conventional MIP particles. Most remarkably, the enantioseparation performance (capacity and... 

Chen et al. reported the enantioseparation of dansyl amino acids on 100 pm i.d. ligand exchange-chiral monolithic microcolumns. Using continuous beds modified with chiral selectors such as L-phenylalanin-amide, L-alaninamide, L-prolinamide, he achieved efficiencies of 1000 plates per meter. 

---