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Light-Driven Catalyst-Free Access to Phthalazines: Entry to Antiviral Model Drugs by Merging Domino Reactions**
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
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
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.
Keywords:Diels-Alder reaction  Light-driven domino reaction  One-pot reaction  Photoenolization  Phthalazines
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