A small-scale synthesis and enantiomeric resolution of (RS)-[1-14C]-2-phenylpropionic acid and biosynthesis of its diastereomeric acyl glucuronides

The 3 step synthesis for (RS)-[1-C-14]-2-phenylpropionic acid having overall yield of 30% is reported. The enantiomers were separated to an optical purity of 95 % (90 % ee) by semi-preparative chiral HPLC using an alpha (1)-acid glycoprotein-based column (which has not previously been reported for this separation). Subsequently, the diastereomeric acyl glucuronides of (R)- and (S)-[1-C-14]-2-phenylpropionic acid were biosynthesised using a recirculating-mode isolated perfused rat liver preparation. The procedure for purification of the glucuronides by semi-preparative HPLC was optimised to ensure the biosynthetic products did not undergo degradation via acyl migration or hydrolysis.