Total Synthesis of Shearinines D and G: A Convergent Approach to Indole Diterpenoids

The first total syntheses of the indole diterpenoids (+)‐shearinine G and D are disclosed. The successful routes rely on late‐stage coupling of two complex fragments. Formation of the challenging trans‐hydrindane motif was accomplished by diastereoselective, intramolecular cyclopropanation. A one‐po...

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Bibliographic Details
Published in:Angewandte Chemie 2022-01, Vol.134 (3), p.n/a
Main Authors: Hauser, Nicole, Imhof, Michael A., Eichenberger, Sarah S., Kündig, Tomas, Carreira, Erick M.
Format: Article
Language:English
Subjects:
alkaloids
Chemistry
Diterpenes
Divergence
natural products
Oxidation
ring synthesis
Stereoselectivity
terpenoids
total synthesis
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Summary:The first total syntheses of the indole diterpenoids (+)‐shearinine G and D are disclosed. The successful routes rely on late‐stage coupling of two complex fragments. Formation of the challenging trans‐hydrindane motif was accomplished by diastereoselective, intramolecular cyclopropanation. A one‐pot sequence consisting of Sharpless dihydroxylation/Achmatowicz reaction was developed to install the dioxabicyclo[3.2.1]octane motif. The indenone subunit was accessed by Prins cyclization. Tuning the electronic nature of the substituents on the parent arylcarboxaldehyde allowed access to divergent products that were further transformed into shearinines G and D. Riley‐type oxidation of a bicyclic enone yielded a surprising stereochemical outcome. Highly convergent total syntheses of (+)‐shearinines G and D, fungal metabolites with interesting bioactivities, were accomplished through late‐stage coupling of two complex fragments. Intramolecular rhodium‐catalyzed cyclopropanation of a diazo ketone established the central trans‐hydrindane motif bearing two vicinal quaternary stereocenters, thus providing a new approach to alkaloids of this type.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202112838