Synthesis of 5-Bromodiffractaic Acid and its Antiviral Properties Against Respiratory Syncytial Virus Strain A2

Abstract

Natural hydroxy acids, in particular lichen depsides, are of considerable interest to medicinal chemistry due to their broad spectrum of biological activity. Diffractaic acid is a secondary lichen metabolite belonging to the class of depsides. Its structure contains two positions available for aromatic substitution, and modification by introducing substituents at these positions has not been previously studied. Two benzene rings of diffractaic acid bear slightly different sets of substituents, so the possibility of performing regioselective introduction of new substituents is not obvious. It is shown that the N-bromosuccinimide based bromination of diffractaic acid is regioselective at the ring bearing a free carboxy group. The structure of 5-bromodiffractaic acid is established by two-dimensional NMR spectroscopy. Introduction of a bromine atom into the diffractaic acid structure significantly increases both the activity against respiratory syncytial virus strain A2 and the chemotherapeutic index, the latter by a factor of six.