Synthesis and biological assessment of 3,7-dihydroxytropolones

D. R. Hirsch; D. V. Schiavone; A. J. Berkowitz; L. A. Morrison; T. Masaoka; J. A. Wilson; E. Lomonosova; H. Zhao; B. S. Patel; S. H. Datla; S. G. Hoft; S. J. Majidi; R. K. Pal; E. Gallicchio; L. Tang; J. E. Tavis; S. F. J. Le Grice; J. A. Beutler; R. P. Murelli

doi:10.1039/C7OB02453C

Synthesis and biological assessment of 3,7-dihydroxytropolones†

D. R. Hirsch,^ab D. V. Schiavone,^ab A. J. Berkowitz,^ab L. A. Morrison,^c T. Masaoka,^d J. A. Wilson,^e E. Lomonosova,^c H. Zhao,^f B. S. Patel,^c S. H. Datla,^c S. G. Hoft,^c S. J. Majidi,^c R. K. Pal,^ag E. Gallicchio,^abg L. Tang,^f J. E. Tavis,^c S. F. J. Le Grice,^d J. A. Beutler

^e and R. P. Murelli*^ab

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* Corresponding authors

^a Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York, USA
E-mail: rpmurelli@brooklyn.cuny.edu

^b PhD Program in Chemistry, The Graduate Center of The City University of New York, New York, New York 10016, USA

^c Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA

^d Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA

^e Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA

^f Department of Molecular Biosciences, The University of Kansas, Lawrence, Kansas 66045, USA

^g PhD Program in Biochemistry, The Graduate Center of The City University of New York, New York, USA

Abstract

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.

Organic & Biomolecular Chemistry

Synthesis and biological assessment of 3,7-dihydroxytropolones†

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Synthesis and biological assessment of 3,7-dihydroxytropolones

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