Acyclic nucleoside bisphosphonates: Synthesis and properties of chiral 2-amino-4,6-bis[(phosphonomethoxy)alkoxy]pyrimidines

2-Amino-4,6-bis[(phosphonomethoxy)alkoxy]pyrimidines bearing two equal or different achiral or chiral phosphonoalkoxy chains have been prepared either by aromatic nucleophilic substitution of 2-amino-4,6-dichloropyrimidine or by alkylation of 4,6-dihydroxy-2-(methylsulfanyl)pyrimidine with appropriate phosphonate-bearing building block. Alkylation of 4,6-dihydroxy-2-(methylsulfanyl)pyrimidine proved to be the method of choice for efficient preparation of variety of bisphosphonates. The enantiomeric purity of selected compounds was determined by capillary electrophoresis. Antiviral activity of bisphosphonates is discussed.

Graphical abstractSynthesis of bisphosphonates by alkylation of 4,6-dihydroxy-2-(methylsulfanyl)pyrimidine with a phosphonate-bearing building block.Figure optionsDownload full-size imageDownload as PowerPoint slide