Elucidation of the enantioselective recognition mechanism of a penicillin G acylase-based chiral stationary phase towards a series of 2-aryloxy-2-arylacetic acids.
A series of structurally related 2-aryloxy-2-arylacetic acids (1-3, 5-16) together with a thioisostere derivative (4) have been synthesized and characterized by GC-MS and 1H NMR. The designed compounds were analyzed on a Penicillin G Acylase chiral stationary phase (PGA-CSP) and the influence of the structure variations on retention and enantioselectivity was investigated. The chromatographic study includes the direct separation of the enantiomers of the synthesized compounds and the determination of the elution order of selected racemic mixtures. 10 out of 16 racemates were separated; high chromatographic enantioseparation factors (alpha > 2) were achieved for some compounds. For the enantiomers of four compounds whose absolute configuration was known (1, 3, 12, 16), the elution order was R:S with the exception of 2-(4-chloro-phenoxy)phenylacetic acid (1), for which the elution order was reversed. Preliminary molecular modeling studies suggest that both polar and charge-transfer interactions as well as steric effects play an important role in determining the retention factors and the enantioselectivities observed.
Massolini
Gabriella
G
Dipartimento di Chimica Farmaceutica, Università di Pavia, Pavia, Italy.
Fracchiolla
Giuseppe
G
Calleri
Enrica
E
Carbonara
Giuseppe
G
Temporini
Caterina
C
Lavecchia
Antonio
A
Cosconati
Sandro
S
Novellino
Ettore
E
Loiodice
Fulvio
F
D019342:Acetic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006860:Hydrogen Bonding; D008024:Ligands; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010399:Penicillin Amidase / Q000737:chemistry*; D013237:Stereoisomerism
D008024:Ligands; D010399:Penicillin Amidase; D019342:Acetic Acid