Synthesis of optically active deuterium‐labeled homocysteine thiolactone

Optically pure ( R )‐ and ( S )‐3‐aminotetradeutero‐2‐thiophenone ( D ‐ and L ‐[ 2 H 4 ]homocysteine thiolactone) for use as substrates for metabolic and pharmacokinetic studies has been prepared. The racemic [ 2 H 4 ]homocysteine thiolactone hydrochloride was prepared from commercially available and highly enriched DL ‐[3,3,4,4‐ 2 H 4 ]methionine by intramolecular condensation with hydriodic acid. The racemate was derivatized with ( S )‐(+)‐2‐methoxyphenylacetic acid to form the diastereomeric amides. The diastereomers were separated by silica gel column chromatography. Hydrolysis of the D‐ and L‐isomer amide in 4 M HCl–ethanol (1:2 v/v) afforded the optically pure D ‐ and L ‐[ 2 H 4 ]homocysteine thiolactone, respectively. Copyright © 2010 John Wiley & Sons, Ltd.