Light-Driven Catalyst-Free Access to Phthalazines: Entry to Antiviral Model Drugs by Merging Domino Reactions** |
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Authors: | Dr. Anton Guryev Florian Schuster Lars Herrmann Dr. Friedrich Hahn Christina Wangen Dr. Jan Hodek Dr. Jan Weber Prof. Dr. Manfred Marschall Prof. Dr. Svetlana B. Tsogoeva |
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Affiliation: | 1. Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander University Erlangen-Nürnberg, Nikolaus Fiebiger-Straße 10, 91058 Erlangen, Germany;2. Institute for Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany;3. Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo náměstí 542/2, 160 00 Praha 6, Czech Republic |
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Abstract: | We report the development of a metal-free four-step one-pot synthetic strategy to access high-value functionalized phthalazines using o-methyl benzophenones as starting compounds. Combining a light-mediated enolization of o-methyl benzophenones/Diels-Alder reaction domino process with a subsequent deprotection/aromatization domino reaction in one-pot leads to sustainable and efficient organic synthesis. The tangible advantages, i. e., absence of catalysts or additives, utilization of commercially available and/or easily accessible substrates, mild reaction conditions, simplicity, and single work-up procedure, make this combined process highly appealing for the direct construction of various 1-aryl-phthalazines. Importantly, in vitro bioactivity evaluation of these newly prepared heterocyclic compounds demonstrated a strong antiviral efficacy against major human pathogens like HCMV and SARS-CoV-2. |
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Keywords: | Diels-Alder reaction Light-driven domino reaction One-pot reaction Photoenolization Phthalazines |
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