Beilstein J. Org. Chem.2022,18, 1466–1470, doi:10.3762/bjoc.18.153
diester (ApppI(d2)) 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
(d2) opens possibilities to quantitative measurements of ApppI in biological samples by mass spectrometry. The synthesized target compound ApppI(d2) was purified by high-performance counter current chromatography and characterized by 1H, 13C, and 31P NMR spectroscopy as well as high-resolution mass
spectrometry.
Keywords: ApppI; ATP; deuterium labelling; HPCCC; mevalonate pathway; NMR; synthesis; Introduction
It has become clear and evident that phosphonate chemistry plays a crucial role in drug research and development [1][2][3][4]. There are several phosphonate-containing compounds under research or
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Graphical Abstract
Figure 1:
Structure of natural pyrophosphate and examples of NBPs (Z = Na or H).
Beilstein J. Org. Chem.2015,11, 2189–2193, doi:10.3762/bjoc.11.237
Janne Weisell Jouko Vepsalainen Petri A. Turhanen University of Eastern Finland, School of Pharmacy, Biocenter Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland 10.3762/bjoc.11.237 Abstract Two strategies for the synthesis of the ATP (adenosine triphosphate) analogue ApppI [1-adenosin-5’-yl 3-(3
-methylbut-3-enyl)triphosphoric acid diester] (1) are described. ApppI is an active metabolite of the mevalonate pathway and thus is of major biological significance. Chemically synthezised ApppI was purified by using triethylammonium bicarbonate as the counter ion in ion-pair chromatography and
characterized by 1H, 13C, 31P NMR and MS spectroscopical methods.
Keywords: ApppI; ATP analogue; HPLC; purification; synthesis; Findings
Bisphosphonates (BPs), which are stable analogues of pyrophosphate occurring in cells, have been used for decades for the treatment of many kinds of bone related diseases