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.