1. TETROFURANOSE NUCLEOSIDE PHOSPHONIC ACIDS: SYNTHESIS AND PROPERTIES.
- Author
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Poláková, Ivana, Buděšínský, Miloš, Točík, Zdeněk, and Rosenberg, Ivan
- Subjects
NUCLEOSIDES ,PHOSPHONIC acids ,PHOSPHORUS compounds ,PYRIMIDINES ,SPECTRUM analysis ,RESPONSE inhibition ,THYMIDINE ,PHOSPHORYLASES ,ENZYME inhibitors - Abstract
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 (K
i = 4 μM). [ABSTRACT FROM AUTHOR]- Published
- 2011
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