Collect. Czech. Chem. Commun. 2011, 76, 503-536
Published online 2011-04-21 07:48:53

Tetrofuranose nucleoside phosphonic acids: Synthesis and properties

Ivana Poláková, Miloš Buděšínský, Zdeněk Točík and Ivan Rosenberg*

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo 2, 16610 Prague 6, Czech Republic


New isoelectronic, non-isosteric phosphonate analogues of nucleoside 5′-phosphates featuring the phosphorus moiety directly attached on the sugar ring in the C4′ position are described. The analogues were synthesised by a nucleosidation reaction from tetrofuranosyl phosphonate synthons and silylated nucleobases. The pyrimidine compounds with erythro and threo configuration in both D- and L-series were prepared, and the structures were assigned by NMR spectroscopy. The results of NMR conformational studies show that all calculated conformers have a maximum pucker in the range typical for nucleosides. In all compounds, the S-type conformer is preferred and is more significant in α-D-threo-compounds. Studies on inhibition of thymidine phosphorylase revealed that one of the prepared phosphonic acids was a competitive inhibitor of the enzyme (Ki = 4 μM).

Keywords: Tetrofuranosyl phosphonate; Nucleotide analogues; NMR spectroscopy; Nucleotides; Phosphorus; Oxidation; Synthesis design; Tetrofuranosyl phosphonate; Nucleotide analogues; Sugar hydroxyphosphonates.

References: 52 live references.