Synthesis and biological assessment of 3,7-dihydroxytropolonesElectronic supplementary information (ESI) available. See DOI: 10.1039/C7OB02453C

• Main Authors: Hirsch, D. R, Schiavone, D. V, Berkowitz, A. J, Morrison, L. A, Masaoka, T, Wilson, J. A, Lomonosova, E, Zhao, H, Patel, B. S, Datla, S. H, Hoft, S. G, Majidi, S. J, Pal, R. K, Gallicchio, E, Tang, L, Tavis, J. E, Le Grice, S. F. J, Beutler, J. A, Murelli, R. P
• Format: Journal Article
• Published: 19.12.2017
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c7ob02453c

3,7-Dihydroxytropolones (3,7-dHTs) are highly oxygenated troponoids that have been identified as lead compounds for several human diseases. To date, structure-function studies on these molecules have been limited due to a scarcity of synthetic methods for their preparation. New synthetic strategies towards structurally novel 3,7-dHTs would be valuable in further studying their therapeutic potential. Here we describe the successful adaptation of a [5 + 2] oxidopyrilium cycloaddition/ring-opening for 3,7-dHT synthesis, which we apply in the synthesis of a plausible biosynthetic intermediate to the natural products puberulic and puberulonic acid. We have also tested these new compounds in several biological assays related to human immunodeficiency virus (HIV), hepatitis B virus (HBV) and herpes simplex virus (HSV) in order to gain insight into structure-functional analysis related to antiviral troponoid development. A new 3,7-dihydroxytropolone synthetic strategy provides access to a proposed natural product precursor and potent antiviral compounds.