Neste trabalho desenvolveu-se um processo alternativo para separação cromatográfica dos enantiômeros (+)-(3R,4R) e ( - )-(3S,4S) do β-aminoácido quiral trans-2,2,5,5-tetrametilpirrolidina-3-amino-4-carboxílico (POAC), que estava protegido no grupo amínico para posterior ligação a um peptídeo, polímero ou outra macromolécula. A enantioseparação foi obtida por HPLC usando uma fase estacionária normal à base de celulose quiral e eluição isocrática. O sistema n-hexano:isopropanol, sempre com maior quantidade do primeiro solvente, foi usado como fase móvel, pois forneceu os melhores resultados na separação dos dois componentes, constatado pelos valores mais elevados de fator de separação e de índice de resolução cromatográfica. Estes parâmetros apresentaram valores de 3,7 e 18,4 e de 2,0 e 6,7 nas soluções com proporção 90:10 (v/v) e 80:20 (v/v) de n-hexano:isopropanol, respectivamente. Estes dados indicam que a estratégia de purificação cromatográfica em uma única etapa usando fase normal é viável, abrindo assim a perspectiva de uma produção rápida e em grande escala desta sonda paramagnética.

In this work an alternative chromatographic process was developed for fractionating the (+)-(3R,4R) and ( - )-(3S,4S) enantiomers of the chiral trans β-amino acid trans-2,2,5,5-tetramethylpyrrolidine-3-amino-4-carboxylic acid (POAC), which was protected at its amine group for further coupling to a peptide, polymer or other macromolecule. The HPLC enantioseparation was achieved using a chiral cellulose-based normal stationary phase and isocratic elution. The n-hexane:isopropanol system, always with greater amount of the former component, was used as mobile phase as revealed by improved fractionation property of both components, demonstrated by the separation factor and resolution index values. These parameters presented values of 3.7 and 18.4 and of 2.0 and 6.7 when in 90:10 (v/v) and 80:20 (v/v) n-hexane:isopropanol solutions, respectively. These findings indicate that the one-step chromatographic purification strategy using normal-phase is feasible, thus opening the perspective of a fast large-scale production this paramagnetic spin probe.

There is great interest nowadays in the use of preparative liquid chromatography as an effective tool for the production of enantiomerically pure, or enriched, compounds for the pharmaceutical industry. To make the chromatographic process economically attractive, attention is now focused on the choice of the chromatographic operating mode to minimize eluent consumption and to maximize productivity. Among the alternatives to the traditional batch chromatography, attention is now shifting towards simulated moving bed (SMB) technologies and a review covering the latest developments in this area seems timely. Several aspects of this important analytical technique are presented and details concerning the SMB technology for process optimization are outlined.