A Bio-Inspired Total Synthesis of Tetrahydrofuran Lignans

Lignan natural products comprise a broad spectrum of biologically active secondary metabolites. Their structural diversity belies a common biosynthesis, which involves regio‐ and chemoselective oxidative coupling of propenyl phenols. Attempts to replicate this oxidative coupling have revealed signif...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2015-02, Vol.54 (7), p.2204-2208
Main Authors: Albertson, Anna K. F., Lumb, Jean-Philip
Format: Article
Language:English
Subjects:
Active control
biomimetic synthesis
Biomimetics
cascade reactions
Coumaric Acids - chemistry
Cyclobutane
Furans - chemical synthesis
Hinges
Joining
Lignans
Lignans - chemical synthesis
Natural products
Oxidation-Reduction
phenolic oxidation
Phenols - chemistry
Ring opening
Synthesis
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Summary:Lignan natural products comprise a broad spectrum of biologically active secondary metabolites. Their structural diversity belies a common biosynthesis, which involves regio‐ and chemoselective oxidative coupling of propenyl phenols. Attempts to replicate this oxidative coupling have revealed significant challenges for controlling selectivity, and these challenges have thus far prevented the development of a unified biomimetic route to compounds of the lignan family. A practical solution is presented that hinges on oxidative ring opening of a diarylcyclobutane to intercept a putative biosynthetic intermediate. The effectiveness of this approach is demonstrated by the first total synthesis of tanegool in 4 steps starting from ferulic acid, as well as a concise synthesis of the prototypical furanolignan pinoresinol. Ringing the changes: A bio‐inspired synthesis of furanolignan natural products that hinges on the oxidative ring opening of diarylcyclobutane diols is reported. The resulting bis‐para‐quinone methides participate in a complex cascade to complete the first total synthesis of tanegool. Modification of the cyclobutane prior to oxidation affords the structurally distinct lignan pinoresinol, thus demonstrating the flexibility of this synthetic strategy.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201408641