Diastereo- and enantioseparation of a Nα-Boc amino acid with a zwitterionic quinine-based stationary phase: Focus on the stereorecognition mechanism

• Published in: Analytica chimica acta 2015-07, Vol.885, p.174-182
• Main Authors: Ianni, Federica, Carotti, Andrea, Marinozzi, Maura, Marcelli, Gloria, Di Michele, Alessandro, Sardella, Roccaldo, Lindner, Wolfgang, Natalini, Benedetto
• Format: Article
• Language: English
• Subjects: Chiral recognition mechanism; Cinchona alkaloid-derived zwitterionic chiral stationary phases; Diastereo- and enantioseparation; Electronic circular dichroism; Pharmaceutically relevant Nα-Boc amino acid; Polar-ionic mode
• ISSN: 0003-2670; 1873-4324
• DOI: 10.1016/j.aca.2015.06.001

[Display omitted] •The ZWIX(+) column allowed getting the Boc-Aph(Hor)-OH (1) isomeric peaks resolved.•ECD studies and molecular dynamic simulations allowed to assign the elution order.•Molecular descriptors revealed the active role of achiral elements of the CSP. A chiral chromatography method enabling the simultaneous diastereo- and enantioseparation of Nα-Boc-N4-(hydroorotyl)-4-aminophenylalanine [Boc-Aph(Hor)-OH, 1] was optimized with a quinine-based zwitterionic stationary phase. The polar-ionic eluent system consisting of ACN:MeOH:water—49.7:49.7:0.6 (v/v/v) with formic acid (4.0mM) and diethylamine (2.5mM), allowed the successful separation of the four acid stereoisomers: αd,d-/d,l-1=1.08; αd,l-/l,d-1=1.08; αl,d-/l,l-1=1.40. According to the in-house developed synthetic procedure and the recorded electronic circular dichroism spectra, the following stereoisomeric elution order was readily established in the optimal chromatographic conditions: d,d-1