Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI( d 2 )

The chemical synthesis of the dideuterium-labelled ATP analogue 1-adenosin-5’-yl-3-(3-methylbut-3-en-1,1- d 2 -1-ol) triphosphoric acid diester (ApppI( d 2 )) is described. ApppI has been reported to be an important mevalonate pathway metabolite, induced by nitrogen-containing bisphosphonates used for the treatment of several diseases related to the calcium metabolism, of which osteoporosis is the most well-known. The availability of ApppI( d 2 ) opens possibilities to quantitative measurements of ApppI in biological samples by mass spectrometry. The synthesized target compound ApppI( d 2 ) was purified by high-performance counter current chromatography and characterized by 1 H, 13 C, and 31 P NMR spectroscopy as well as high-resolution mass spectrometry.