Enantiomeric separation of 2-aryloxyalkyl- and 2-arylalkyl-2-aryloxyacetic acids on a Penicillin G Acylase-based chiral stationary phase: Influence of the chemical structure on retention and enantiose
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- 作者：Caterina Temporini ; Enrica Calleri ; Giuseppe Fracchiolla ; Giuseppe Carbonara ; Fulvio Loiodice ; Antonio Lavecchia ; Paolo Tortorella ; Gloria Brusotti ; Gabriella Massolini
- 关键词：Chiral HPLC ; Monolithic PGA column ; Enantiomeric discrimination ; Molecular modelling
- 刊名：Journal of Pharmaceutical and Biomedical Analysis
- 出版年：2007
- 出版时间：18 October 2007
- 年：2007
- 卷：45
- 期：2
- 页码：211-218
- 全文大小：979 K
文摘
The chiral recognition mechanism of Penicillin G Acylase (PGA) was investigated with a set of 18 new chiral acidic compounds. A series of 2-aryloxyalkyl- and 2-arylalkyl-2-aryloxyacetic acids in which the absolute configuration has been reported to exert a strong influence on pharmacological activity, were synthesized and analysed on PGA-based chiral stationary phase (CSP) and 11 racemates were completely resolved with a mobile phase composed of 50 mM phosphate buffer (pH 7.0). The influence of structural variations of analytes on retention and enantioselectivity was investigated by application of molecular modelling studies. Docking experiments were also carried out to rationalize the observed enantioselective behaviour. The computation approach revealed to be helpful in elucidating the molecular basis of the enantioselectivity observed on PGA-CSP.