Synthesis of 5-Substituted 2′-Deoxyuridine-5′- Phosphonate Analogues and Evaluation of their Antiviral Activity

Abstract

A small series of 5-(hetero)aryl-modified nucleoside phosphonates was synthesized via an 8-step procedure including a Wittig reaction and Suzuki–Miyaura coupling. An unanticipated anomerization during phosphonate deprotection allowed us to isolate both anomers of the 5-substituted 2′-deoxy-uridine phosphonates and assess their antiviral activity against a broad panel of viruses.

Keywords:

• Antiviral nucleoside analogues
• pyrimidine modification
• phosphonates
• α-nucleosides
• antiviral activity

Acknowledgments

We thank the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT) for providing a scholarship to SVP. The antiviral research was supported by the K.U.Leuven (GOA no. 10/14). We also thank Leen Ingels, Leentje Persoons, Frieda De Meyer, Anita Camps, Lies Van den Heurck, and Steven Carmans for technical assistance in the antiviral experiments; and Izet Karalic for assistance with the preparative HPLC purification.