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

Abstract

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.