Synthesis of deuterium-labelled 5'-O-[N-(Salicyl)sulfamoyl]adenosine (Sal-AMS-d(4)) as an internal standard for quantitation of Sal-AMS.

5'-O-[N-(Salicyl)sulfamoyl]adenosine (Sal-AMS, 1) is a potent inhibitor of the bifunctional enzyme salicyl-AMP ligase in Mycobacterium tuberculosis. This inhibitor acts by disrupting the biosynthesis of the mycobactin siderophores that are essential for the process of iron acquisition. To aid with in vitro metabolism and in vivo pharmacokinetic studies of Sal-AMS, a stable deuterium-labelled Sal-AMS analog (Sal-AMS-d(4)) was synthesized. This deuterium-labelled analog was used as an internal standard to conduct in vitro plasma and microsomal stability studies. Sal-AMS was found to be stable for 24 h in human plasma and 1 h in human liver microsomes at 37 degrees C.