Highly Functionalized and Potent Antiviral Cyclopentane Derivatives Formed by a Tandem Process Consisting of Organometallic,Transition‐Metal‐Catalyzed,and Radical Reaction Steps |
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| Authors: | Pratap R. Jagtap Dr. Leigh Ford Dipl.‐Chem. Elmar Deister Dr. Radek Pohl Dr. Ivana Císařová Jan Hodek Dr. Jan Weber Dr. Richard Mackman Dr. Gina Bahador Dr. Ullrich Jahn |
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| Affiliation: | 1. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo namesti 2, 16610 Prague (Czech Republic);2. Present Address: Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, Victoria (Australia);3. Institut für Organische Chemie, Technische Universit?t Braunschweig, Hagenring 30, 38106 Braunschweig (Germany);4. Department of Inorganic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12843 Prague 2 (Czech Republic);5. Gilead Sciences, Inc. 333 Lakeside Drive, Foster City, CA 94404 (USA) |
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| Abstract: | A simple modular tandem approach to multiply substituted cyclopentane derivatives is reported, which succeeds by joining organometallic addition, conjugate addition, radical cyclization, and oxygenation steps. The key steps enabling this tandem process are the thus far rarely used isomerization of allylic alkoxides to enolates and single‐electron transfer to merge the organometallic step with the radical and oxygenation chemistry. This controlled lineup of multiple electronically contrasting reactive intermediates provides versatile access to highly functionalized cyclopentane derivatives from very simple and readily available commodity precursors. The antiviral activity of the synthesized compounds was screened and a number of compounds showed potent activity against hepatitis C and dengue viruses. |
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| Keywords: | antiviral activity cyclopentanes isomerization organic synthesis radicals |
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