Preparation of acyclo nucleoside phosphonate analogues based on cross-metathesis

In our on-going program targeting anti-pox activity, we report here the synthesis of hitherto unknown acyclic nucleoside phosphonates using olefin cross-metathesis (CM) as a key assembly step. Modification at the C-5 position of the uracil moiety was performed under optimized Pd(0)-catalyzed Stille cross-coupling conditions. None of the obtained compounds were active against poxviruses, nor do they exhibit any toxicity.

Graphical abstractIn our on-going program targeting anti-pox activity, the synthesis of various acyclic nucleoside phosphonates is described using olefin cross-metathesis reaction and Pd(0)-mediated alkylation at the C5-position of the uracil moiety. Download full-size image