Sonication‐Assisted Synthesis of (E)‐2‐Methyl‐but‐2‐enyl Nucleoside Phosphonate Prodrugs

Several hitherto unknown acyclic 2‐methyl‐but‐2‐enyl nucleoside phosphonate analogs (ANPs) and their bis‐(pivaloyloxymethyl) prodrug forms were prepared by a challenging ultrasonic‐assisted olefin cross metathesis and further modifications under microwaves, giving rise to a small library of title compounds. These ANPs were evaluated against a wide spectrum of DNA/RNA viruses. Among them, the most active compound exhibited a micromolar anti‐HIV‐1 activity with an EC50 of 1.1 µM and an EC90 of 4.2 µM. Several hitherto unknown acyclic 2‐methyl‐but‐2‐enyl nucleoside phosphonate analogs (ANPs) and their bis‐POM prodrug forms were prepared by a challenging olefin cross metathesis (CM) ultrasonic irradiation, giving rise to a small library of title compounds, which were evaluated against a wide spectrum of DNA/RNA viruses. Among them, the most active compound exhibited a micromolar anti‐HIV‐1 activity with an EC50 of 1.1 µM and an EC90 of 4.2 µM. Docking studies corroborate favorable binding to the active site of HIV‐RT, providing a basis for the design of more potent analogues.