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Synthesis Strategies for Hyperforin: Literature Review and Meeting Highlights

Exploring synthesis approaches for hyperforin and related phloroglucins, outlining research by various authors and strategies discussed. Meeting notes from Jad Tannous on January 16, 2006.

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Synthesis Strategies for Hyperforin: Literature Review and Meeting Highlights

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  1. Studies Directed Toward Synthesis of Hyperforin and Related Phloroglucins Literature Meeting Jad Tannous January 16, 2006

  2. Outline • Introduction on the molecules • Hyperforin • Biosynthesis of Hyperforin • Kraus Synthesis of the Bicylic Core • Young Synthesis of the Bicylic Core • My Research at Merck • Garsubellin A • Takagi Development of the Bicyclo[3.3.1]nonenone Core • Miesch New Cascade Reactions Starting from Acetylenic w-ketoesters • Stoltz Progress Toward the Synthesis of Garsubellin A • Nicolaou Synthesis of a Fully Fonctionalized Bicyclic Core • Shibasaki Synthesis of (±)-Garsubellin A

  3. The Molecules: Phloroglucins

  4. The Molecules: More Phloroglucins

  5. Biosynthesis of Hyperforin:Biosynthesis of the hyperforin skeleton in Hypericum calycinum cell cultures

  6. Biosynthesis of Hyperforin:First prenylation step

  7. Biosynthesis of Hyperforin:Hypothetical mechanism of hyperforin biosynthesis

  8. Authors Who Have Worked on Synthesis of Phloroglucins Hyperforin: Kraus, Nicolaou, Young, Metha (enantioselective), … Garsubellin A: Stoltz, Nicolaou, Shibasaki, Grossman, …

  9. Studies toward HyperforinWhat are the strategies? • Kraus: Allylation followed by Mn-mediated oxidative cyclization • Nicolaou: annulation of the gem-dimethyl-containing ring onto an existing cyclohexanone • Young: Intramolecular allene-nitrile oxide cycloaddition

  10. Kraus Synthesis of the Bicylic Core

  11. Young Synthesis of the bicylic core

  12. Young Synthesis of the bicylic core

  13. My Research at Merck

  14. My Research at Merck

  15. Synthesis and Studies toward Garsubellin AWhat are the strategies? • Shibasaki: C-C bond forming addition-elimination and aldol reactions • Nicolaou: « Biomimetic » selenocyclization of a cyclic B-keto ester onto a pendant prenyl group • Stoltz: Tandem Claisen-Dieckmann reaction of malonyl dichloride

  16. Takagi Development of the Bicyclo[3.3.1]nonenone Core

  17. Takagi Development of the Bicyclo[3.3.1]nonenone Core

  18. Miesch New Cascade Reactions Starting from Acetylenic w-ketoesters

  19. Miesch New Cascade Reactions Starting from Acetylenic w-ketoesters

  20. Stoltz Progress Toward the Synthesis of Garsubellin A

  21. Stoltz Progress Toward the Synthesis of Garsubellin A

  22. Nicolaou Synthesis of a Fully Fonctionalized Bicyclic Core

  23. Nicolaou Synthesis of a Fully Fonctionalized Bicyclic Core

  24. Nicolaou Synthesis of a Fully Fonctionalized Bicyclic Core

  25. NicolaouHighly Functionalized Medium-Sized Rings

  26. Shibasaki Retrosynthetic Analysis

  27. Shibasaki Synthesis of (±)-Garsubellin A

  28. Shibasaki Synthesis of (±)-Garsubellin A

  29. Shibasaki Synthesis of (±)-Garsubellin A

  30. Mechanism of the Wacker Oxidation:

  31. Shibasaki Synthesis of (±)-Garsubellin A

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