Preparation of 1-0-acylglucuronides of 13C-labelled (R)- and (S)-ketoprofens

Article abstract of DOI:10.1002/(SICI)1099-1344(199705)39:5<353::AID-JLCR980>3.0.CO;2-X

The preparation of enantiomeric [1-¹³C]ketoprofens (KPs) and their acylglucuronides has been reported for the nuclear magnetic resonance (NMR) spectroscopic studies on the stereoselective pharmacokinetics and reactivities of KP acylglucuronides. The racemic [1-¹³]KP was prepared by a three-step synthetic scheme from [¹³C]potassium cyanide in overall yield of 23 %. The racemate was optically resolved by the formation of diastereomeric amides with (R)-(+)-α-phenylethylamine, separation of the amides by column chromatography on silica gel, and nonhydrolytic cleavage of the amide bond using nitrogen tetroxide. The yields of KP enantiomers were 30 % based on the racemate. The acylglucuronides of (R)- and (S)-[1-¹³C]KP were isolated from human urine after dosing of each labelled KP (100 mg) using preparative high-performance liquid chromatography following Sep-Pak C₁₈ pretreatments. The yields of the conjugates from 0-4 h post-dose urine were roughly 50 mg.