Preparation of mixed trialkyl alkylcarbonate derivatives of etidronic acid via an unusual route

• Petri A. Turhanen,
• Janne Weisell and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2012, 8, 2019–2024, doi:10.3762/bjoc.8.228

• mechanism is discussed to explain these methyl substitutions. These unusual reactions also clarify why it is difficult to prepare alkylcarbonate prodrugs from bisphosphonates. The compounds prepared were analysed by spectroscopic techniques. Keywords: alkyl carbonate; bisphosphonate; etidronate; ester

• as biodegradable prodrugs of etidronate [11]. Previously, we also synthesized the first phosphorous end-modified alkyl carbonate derivative of HEBPA by a surprising route [18]. According to a SciFinder search, this is the only reported phosphorous end-modified BP carbonate derivative in the

• biodegradable derivatives of BPs. One rather straightforward way to improve the lipophilicity of these compounds is to prepare alkyl carbonate derivatives of BPs. Alkyl carbonate derivatives of phenol and naphthols have been reported to undergo chemical and enzymatic hydrolysis [21][22] and so they have been