Synthesis and antiviral properties of biomimetic iminosugar-based nucleosides

Herein we report the synthesis, conformational analysis and the evaluation of the antiviral activity of six-membered nucleoside analogues having a piperidine ring as the preorganized (deoxy)ribose bioisostere. Mutagenic nucleobase-containing nucleosides 1 and 2 were obtained by appropriate manipulation of the well-known glycomimetic agent deoxynojirimycin as easily accessible starting material. In vitro assays revealed activity of 5-iododeoxyuridine analogue 1 against all DNA viruses tested. As suggested by DFT analysis and pH-dependent NMR experiments, antiviral activity was correlated to the biomimetic character of the piperidine ring, as it is able to resemble the deoxyribose conformations adopted by natural nucleosides when interacting with viral enzymes.

Automated summary

In this study, six-membered nucleoside analogues with a piperidine ring as the preorganized (deoxy)ribose bioisostere were synthesized and evaluated for their antiviral activity. The 5-iododeoxyuridine analogue showed activity against all tested DNA viruses. DFT analysis and pH-dependent NMR experiments suggested that the antiviral activity was attributed to the biomimetic character of the piperidine ring, which can mimic the conformation of natural nucleosides when interacting with viral enzymes.