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

The 3 step synthesis for (RS)-[1-C-14]-2-phenylpropionic acid having overal l yield of 30% is reported. The enantiomers were separated to an optical pu rity of 95 % (90 % ee) by semi-preparative chiral HPLC using an alpha (1)-a cid glycoprotein-based column (which has not previously been reported for t his separation). Subsequently, the diastereomeric acyl glucuronides of (R)- and (S)-[1-C-14]-2-phenylpropionic acid were biosynthesised using a recirc ulating-mode isolated perfused rat liver preparation. The procedure for pur ification of the glucuronides by semi-preparative HPLC was optimised to ens ure the biosynthetic products did not undergo degradation via acyl migratio n or hydrolysis.