Synthesis and antiviral evaluation of cyclopentyl nucleoside phosphonates.

The synthesis of both 2'-hydroxy-3'-deoxy and 2'-deoxy-3'-hydroxy cyclopentyl nucleoside phosphonates with the natural nucleobases adenine, thymine, cytosine and guanine from a single precursor has been performed. The guanine containing analogues showed antiviral activity. Especially the 3'-deoxy congener 23 was active, displaying an EC50 of 5.35 μM against TK+ VZV strain and an EC50 of 8.83 μM against TK- VZV strain, besides lacking cytotoxicity. However, the application of phosphonodiamidate prodrug strategy did not lead to a boost in antiviral activity.