Synthesis of medronic acid monoesters and their purification by high-performance countercurrent chromatography or by hydroxyapatite

• Elina Puljula,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2016, 12, 2145–2149, doi:10.3762/bjoc.12.204

• Elina Puljula Jouko Vepsalainen Petri A. Turhanen School of Pharmacy, University of Eastern Finland, Biocenter Kuopio, P.O.Box 1627, FI-70211 Kuopio, Finland 10.3762/bjoc.12.204 Abstract We achieved the synthesis of important medronic acid monoalkyl esters via the dealkylation of mixed trimethyl

• monoalkyl esters of medronic acid. Two methods were developed for the purification of medronic acid monoesters: 1) small scale (10–20 mg) purification by using hydroxyapatite and 2) large scale (tested up to 140 mg) purification by high-performance countercurrent chromatography (HPCCC). Keywords

• : bisphosphonate; bisphosphonate monoester; high performance counter current chromatography; hydroxyapatite; medronic acid; Introduction Bisphosphonates (BPs) have been used for decades in the treatment of bone-related diseases as well as for bone imaging. Nevertheless, several recent reports have demonstrated