Synthesis of fluorinated acyclic nucleoside phosphonates with 5-azacytosine base moiety

0511182 - FZÚ 2020 RIV GB eng J - Journal Article
Pomeisl, Karel - Krečmerová, M. - Pohl, R. - Snoeck, R. - Andrei, G.
Synthesis of fluorinated acyclic nucleoside phosphonates with 5-azacytosine base moiety.
Tetrahedron. Roč. 75, č. 39 (2019), s. 1-13, č. článku 130529. ISSN 0040-4020. E-ISSN 1464-5416
Institutional support: RVO:68378271
Keywords : acyclic nucleoside phosphonates * 5-Azacytosine * fluorinated nucleotides * prodrugs * phosphonates
OECD category: Organic chemistry
Impact factor: 2.233, year: 2019
Method of publishing: Limited access
https://doi.org/10.1016/j.tet.2019.130529

With respect to the strong antiviral activity of (S)-1-[3-hydroxy- 2-(phosphonomethoxy)propyl]-5-azacytosine various types of its side chain fluorinated analogues were prepared. The title compound, (S)-1-[3-fluoro-2-(phosphonomethoxy)propyl]-5-azacytosine (FPMP-5-azaC) was synthesised by the condensation reaction of (S)-2-[(diisopropoxyphosphoryl)methoxy)-3-fluoropropyl p-toluenesulfonate with a sodium salt of 5-azacytosine followed by separation of appropriate N1 and O2 regioisomers and ester hydrolysis. Antiviral activity of all newly prepared compounds was studied. FPMP-5-azaC diisopropyl ester inhibited the replication of herpes viruses with EC50 values that were about three times higher than that of the reference anti-HCMV drug ganciclovir without displaying cytotoxicity.

Permanent Link: http://hdl.handle.net/11104/0301517