Sonication‐Assisted Synthesis of <i>(E)</i> ‐2‐Methyl‐but‐2‐enyl Nucleoside Phosphonate Prodrugs

Abstract

Abstract 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 EC 50 of 1.1 µM and an EC 90 of 4.2 µM.