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Synfacts 2025; 21(10): 983
DOI: 10.1055/a-2680-8758
Synthesis of Natural Products

Total Synthesis of (–)-Scabronine G

Authors

Waters SP, Tian Y, Li Y-M, Danishefsky SJ *. Sloan-Kettering Institute for Cancer Research and Columbia University, New York, USA
Total Synthesis of (–)-Scabronine G, an Inducer of Neurotrophic Factor Production.

J. Am. Chem. Soc. 2005;
127: 13514-13515
DOI: 10.1021/ja055220x
CrossrefPubMedSearch in Google Scholar
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Keywords

(–)-scabronine G - cyathane diterpenoids - Nazarov cyclization - Nagata hydrocyanation - Negishi cross-coupling - Claisen condensation - Hg-catalyzed one-carbon ring expansion

Significance

Danishefsky and co-workers report the first enantioselective total synthesis of (–)-scabronine G. This cyathane diterpenoid has been isolated from the bitter mushroom Sarcodon scabrosus and presents an interesting target for synthetic and biological studies due to its neurotrophic properties. In addition to the synthesis of (–)-scabronine G, Danishefsky and co-workers were able to show significant neurite outgrowth in cells treated with the natural product, which could be relevant for the treatment of neurodegenerative diseases.


 

Comment

Ketal-protected Wieland–Miescher ketone A serves as a starting point for the synthesis and enables access to tricycle C via Nazarov cyclization. Nagata hydrocyanation with concomitant trapping of the resulting enolate and Negishi cross-coupling yields nitrile F. A series of functional group interconversions followed by Claisen and propanethiol condensation leads to key-step precursor H. Hg-catalyzed one-carbon ring expansion according to a report by Guerrero and co-workers yields tricycle K containing the full carbon skeleton of the natural product.


 

 

Publication History

Article published online:
23 September 2025

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