Lipase-mediated enantioselective kinetic resolution of racemic acidic drugs in non-standard organic solvents: Direct chiral liquid chromatography monitoring and accurate determination of the enantiomeric excesses.
The enantioselective resolution of a set of racemic acidic compounds such as non-steroidal anti-inflammatory drugs (NSAIDs) of the group arylpropionic acid derivatives is demonstrated. Thus, a set of lipases were screened and manipulated in either the esterification or hydrolysis mode for the enantioselective kinetic resolution of these racemates in non-standard organic solvents. The accurate determination of the enantiomeric excesses of both substrate and product during such reaction is demonstrated. This was based on the development of a direct and reliable enantioselective high performance liquid chromatography (HPLC) procedure for the simultaneous baseline separation of both substrate and product in one run without derivatization. This was achieved using the immobilized chiral stationary phase namely Chiralpak IB, a 3,5-dimethylphenylcarbamate derivative of cellulose (the immobilized version of Chiralcel OD) which proved to be versatile for the monitoring of the lipase-catalyzed kinetic resolution of racemates in non-standard organic solvents.
Ghanem
Ashraf
A
Australian Centre for Research on Separation Science, School of Chemistry, University of Tasmania, Private Bag 75, Hobart, Tasmania 7001, Australia. aghanem@utas.edu.au
Aboul-Enein
Mohammed Nabil
MN
El-Azzouny
Aida
A
El-Behairy
Mohammed F
MF
D000143:Acids / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004951:Esterification; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000737:chemistry*; D009930:Organic Chemicals / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000302:isolation & purification; D048448:Phenylcarbamates / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism
C504080:3,5-dimethylphenylcarbamate; D000143:Acids; D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D048448:Phenylcarbamates; D012997:Solvents; D008049:Lipase