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Direct chromatographic enantioresolution of fully constrained β-amino acids: exploring the use of high-molecular weight chiral selectors

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Abstract

To the best of our knowledge enantioselective chromatographic protocols on β-amino acids with polysaccharide-based chiral stationary phases (CSPs) have not yet appeared in the literature. Therefore, the primary objective of this work was the development of chromatographic methods based on the use of an amylose derivative CSP (Lux Amylose-2), enabling the direct normal-phase (NP) enantioresolution of four fully constrained β-amino acids. Also, the results obtained with the glycopeptide-type Chirobiotic T column employed in the usual polar-ionic (PI) mode of elution are compared with those achieved with the polysaccharide-based phase. The Lux Amylose-2 column, in combination with alkyl sulfonic acid containing NP eluent systems, prevailed over the Chirobiotic T one, when used under the PI mode of elution, and hence can be considered as the elective choice for the enantioseparation of this class of rigid β-amino acids. Moreover, the extraordinarily high α (up to 4.60) and R S (up to 10.60) values provided by the polysaccharidic polymer, especially when used with camphor sulfonic acid containing eluent systems, make it also suitable for preparative-scale enantioisolations.

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Abbreviations

AcOH:

Acetic acid

CSA:

Camphorsulfonic acid

CSPs:

Chiral stationary phases

DCM:

Dichloromethane

ESA:

Ethanesulfonic acid

EtOH:

Ethanol

MeOH:

Methanol

MSA:

Methanesulfonic acid

NP:

Normal-phase

PI:

Polar-ionic

PO:

Polar-organic

SAX:

Strong anion exchange

TFA:

Trifluoroacetic acid

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Acknowledgments

Fondazione Cassa di Risparmio is gratefully acknowledged for the financial support of the project “Processi ecosostenibili per la produzione e l’analisi di molecule di interesse farmaceutico” (grant 2012.0114.021).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Perugia, Via Fabretti 48, 06123, Perugia, Italy

    Roccaldo Sardella, Federica Ianni, Antonella Lisanti, Stefania Scorzoni, Francesca Marini, Silvia Sternativo & Benedetto Natalini

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  1. Roccaldo Sardella
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  2. Federica Ianni
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  3. Antonella Lisanti
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  4. Stefania Scorzoni
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  5. Francesca Marini
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  7. Benedetto Natalini
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Correspondence to Benedetto Natalini.

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Sardella, R., Ianni, F., Lisanti, A. et al. Direct chromatographic enantioresolution of fully constrained β-amino acids: exploring the use of high-molecular weight chiral selectors. Amino Acids 46, 1235–1242 (2014). https://doi.org/10.1007/s00726-014-1683-5

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  • DOI: https://doi.org/10.1007/s00726-014-1683-5

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