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Preparation of 1‐ O ‐acylglucuronides of 13 C‐labelled ( R )‐ and ( S )‐ketoprofens
Author(s) -
Akira Kazuki,
Taira Tadaaki,
Hasegawa Hiroshi,
Shinohara Yoshihiko
Publication year - 1997
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199705)39:5<353::aid-jlcr980>3.0.co;2-x
Subject(s) - chemistry , enantiomer , diastereomer , amide , chromatography , carbon 13 nmr , column chromatography , stereoselectivity , high performance liquid chromatography , yield (engineering) , organic chemistry , stereochemistry , catalysis , materials science , metallurgy
The preparation of enantiomeric [1‐ 13 C]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 C]KP was prepared by a three‐step synthetic scheme from [ 13 C]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‐ 13 C]KP were isolated from human urine after dosing of each labelled KP (100 mg) using preparative high‐performance liquid chromatography following Sep‐Pak C 18 pretreatments. The yields of the conjugates from 0–4 h post‐dose urine were roughly 50 mg. © 1997 John Wiley & Sons, Ltd.