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 N 1 and O 2 regioisomers and ester hydrolysis. Transformations of FPMP-5-azaC to its 5,6-dihydro-5-azacytosine counterpart, amino acid phosphoramidate prodrugs and systems with an annelated five-membered imidazole ring, i.e. imidazo [1,2-a][1,3,5]triazine derivatives were also carried out. 1-(2-Phosphonomethoxy-3,3,3-trifluoropropyl)-5-azacytosine was prepared from 5-azacytosine and trifluoromethyloxirane to form 1-(3,3,3-trifluoro-2-hydroxypropyl)-5-azacytosine which was treated with diisopropyl bromomethanephosphonate followed by deprotection of esters. 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.

• Keywords
• 5-Azacytosine, Acyclic nucleoside phosphonates, Fluorinated nucleotides, Phosphonates, Prodrugs,
• Publication type
• Journal Article MeSH

The enzymatic regioselective monopalmitoylation of racemic 9-(2,3-dihydroxypropyl)- adenine (DHPA), an approved antiviral agent, has been performed by an immobilized form of Candida antarctica B lipase (CAL-B) using a 4:1 DMF/hexane mixture as the reaction medium. To improve the chemical yield of the desired monopalmitoylation reaction, solid-phase chemical modifications of the lipase were evaluated. The reaction yield was successfully increased obtaining 100% product after a second treatment of the product solution with fresh immobilised chemically glycosylated-CAL-B.

• Keywords
• chemical modification, glycosylation, palmitoylation, regioselectivity,
• MeSH
• Adenine analogs & derivatives   chemistry   MeSH
• Candida enzymology   MeSH
• Enzymes, Immobilized chemistry   MeSH
• Fungal Proteins chemistry   MeSH
• Glycosylation MeSH
• Hexanes chemistry   MeSH
• Catalysis * MeSH
• Lipase chemistry   MeSH
• Lipoylation MeSH
• Polymers chemistry   MeSH
• Solvents chemistry   MeSH
• Stereoisomerism MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 9-(2,3-dihydroxypropyl)adenine MeSH Browser
• Adenine MeSH
• Enzymes, Immobilized MeSH
• Fungal Proteins MeSH
• Hexanes MeSH
• Lipase MeSH
• lipase B, Candida antarctica MeSH Browser
• n-hexane MeSH Browser
• Polymers MeSH
• Solvents MeSH