Nucleosides Modified at the Base Moiety

A general approach to the synthesis of 5-S-functionalized pyrimidine nucleosides and their analogues

“…Silica gel 40-100 μm was used for column chromatography; precoated silica gel 60 F 254 plates were used for TLC. 1 H NMR (400 MHz) and 13 C NMR (100.6 MHz) spectra were taken on a Bruker Avance III spectrometer. Peaks of residual protons of deuterated solvents or TMS signal were used as chemical shift references.…”

“…R f 0.4 (hexane-ethyl acetate, 5 : 1). 1 H NMR (CDCl 3 , 400 MHz) δ 5.95 (m, 1H), 3.91 (ddd, J = 11.9, 9.1, 3.1 Hz, 1H), 3.73-3.64 (m, 1H), 2.10 (s, 3H), 1.90-1.75 (m, 2H), 1.73-1.47 (m, 4H). 13 C NMR (CDCl 3 , 100.6 MHz) δ 170.02, 92.82, 63.53, 29.33, 25.06, 21.35, 18.86.…”

“…R f 0.50 (dichloromethane-methanol, 10 : 1). 1 Following the same procedure, 5-bromo-2′,3′-dideoxy-3′thiacytidine (3a) was obtained from 2′,3′-dideoxy-3′-thiacytidine (lamivudine, 1a) in 55% yield as a colourless solid. R f 0.35 (dichloromethane-methanol, 10 : 1).…”

“…Structural modifications of these molecules are of great practical importance, making it possible to expand the number of compounds with antitumour or antiviral activity, and/or to adjust pharmacological properties of the parent compounds. 1 One of the modifications of substantial interest is the introduction of S-functionality into a nucleobase ring. For instance, double-stranded RNAs modified at the 5-position by selective thiolation of some cytosine bases have shown high activity against HIV-1 in human cells and against DNA polymerases of DNA and RNA tumours.…”

Enantiomerically Pure Phosphonated Carbocyclic 2'-Oxa-3'-Azanucleosides: Synthesis and Biological Evaluation

“…Continuous efforts in the development of new antiviral agents are a consequence of the urgent demand for new therapeutic agents in which improved biological activity against viruses is matched with low toxicity towards host cells. In this context, particular interest has been focused on the synthesis and the biological activity of nucleoside analogues, in which structural modifications of the heterocyclic bases and/or the sugar moiety of natural nucleosides have been performed [1,2,3,4,5,6,7,8,9,10,11,12,13]. A remarkable impulse for research on nucleoside analogues arose from the urgent need to find a therapeutic approach to combat human immunodeficiency virus (HIV) infections.…”