A Concise Synthesis of Forskolin

A 24‐step synthesis of (±)‐forskolin is presented, which delivered hundred milligram quantities of this complex diterpene in one pass. Transformations key to our approach include: a) a strategic allylic transposition, b) stepwise assembly of a sterically encumbered isoxazole ring, and c) citric acid...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2017-10, Vol.56 (41), p.12586-12589
Main Authors: Hylse, Ondřej, Maier, Lukáš, Kučera, Roman, Perečko, Tomáš, Svobodová, Aneta, Kubala, Lukáš, Paruch, Kamil, Švenda, Jakub
Format: Article
Language:English
Subjects:
adenylyl cyclases
Citric acid
Forskolin
natural product synthesis
Semisynthesis
structural analogues
Synthesis
Transposition
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Summary:A 24‐step synthesis of (±)‐forskolin is presented, which delivered hundred milligram quantities of this complex diterpene in one pass. Transformations key to our approach include: a) a strategic allylic transposition, b) stepwise assembly of a sterically encumbered isoxazole ring, and c) citric acid‐modified Upjohn dihydroxylation of a resilient tetrasubstituted olefin. The developed route has exciting potential for the preparation of new forskolin analogues inaccessible by semisynthesis. Forskolin is a complex diterpene commonly used in biomedical research to raise levels of cAMP. Previous strategies to access forskolin analogues with improved properties focused primarily on semisynthesis. To complement these approaches, the chemical synthesis of forskolin was streamlined and applied to the preparation of fully synthetic forskolin analogues.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201706809