Separation of the stereoisomers of the main metabolite of a non-steroidal anti-inflammatory drug, flobufen (cas 112344-52-2), by chiral high-performance liquid chromatography

Add time:07/23/2019    Source:sciencedirect.com

The major metabolite of a novel non-steroidal anti-inflammatory drug, dl-4-(2′-4′-difluorobiphenyl-4-yl)-4-oxo-2-methylbutonoic acid (flobufen, I), namely 4-(2′,4′-difluorobiphenyl-4-yl)-2-methyl-γ-butyrolactone (4-dihydroflobufen lactone, III), has four stereoisomers consisting of two racemic pairs of enantiomers. Of three chiral stationary phases tested, Cyclobond I β-RSP (Astec) (β-cylodextrin derivatized with R,S-hydroxypropyl) was best able to separate the (++)(−−) racemate, with a liquid phase containing acetonitrile as modifier and triethylamine acetate as buffer. Using the Box-Wilson Central Composite Design for three factors, an optimum combination of pH and concentrations of the modifier and buffer was eventually obtained. A chromatographic response function based on a combination of the Kaiser peak separation function, Pi, and retention time of the second eluting enantiomer, tRL, served as a response criterion for the process of optimization. The optimum conditions developed for the (++)(−−) racemate were also found to be suitable for separating the (+−)(−+) racemate, for which earlier studies had shown the separation to be more facile. Separation of the four stereoisomers of III, for which the chiral chromatographic system optimized in this study is proposed as the second stage, is targeted at a biochemical study of the stereoisomeric metabolism of I.

We also recommend Trading Suppliers and Manufacturers of flobufen (cas 112344-52-2). Pls Click Website Link as below: cas 112344-52-2 suppliers

Prev:Metabolic pathways of flobufen (cas 112344-52-2) — a new antirheumatic and antiarthritic drug. Interspecies comparison
Next:Zirconocene-catalyzed epoxy ester - ortho ester rearrangement: A new method for the protection of polyfunctionalized carboxylic acids and the asymmetric synthesis of ortho esters)