Collect. Czech. Chem. Commun. 2011, 76, 1187-1198
Published online 2011-09-20 09:01:13

Efficient synthesis and biological properties of the 2′-trifluoromethyl analogues of acyclic nucleosides and acyclic nucleoside phosphonates

Petr Jansa*, Viktor Kolman, Alexandra Kostinová, Martin Dračínský, Helena Mertlíková-Kaiserová and Zlatko Janeba

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic


Efficient and optimized procedure for the preparation of several acyclic nucleosides and acyclic nucleoside phosphonates substituted at the C-2′ position of the aliphatic part by the trifluoromethyl group is described. Trifluoromethyloxirane was found to be an excellent reagent for the introduction of the 1,1,1-trifluoropropan-2-ol moiety. Surprisingly, the next reaction of these 1,1,1-trifluoropropan-2-ols with the reagent for the introduction of the methylphosphonic residue afforded the desired phosphonates in very high yields and finally a novel simple and scalable procedure for the isolation of free phosphonic acids, after the reaction of dialkyl phosphonates with bromotrimethylsilane, was developed. Prepared compounds were evaluated for their biological properties, but none of the prepared phosphonic acids or acyclic nucleosides exhibits any antiviral, antiproliferative or anti-toxin activities.

Keywords: Nucleosides; Nucleotides; Phosphorus; Fluorine; Biological activity; Antibiotics.

References: 28 live references.