Synfacts 2014; 10(10): 1005
DOI: 10.1055/s-0034-1379078
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of (+)-Cavicularin

Contributor(s):
Erick M. Carreira
,
Christian Ebner
Zhao P, Beaudry CM * Oregon State University, Corvallis, USA
Enantioselective and Regioselective Pyrone Diels–Alder Reactions of Vinyl Sulfones: Total Synthesis of (+)-Cavicularin.

Angew. Chem. Int. Ed. 2014;
DOI: 10.1002/anie.201406621.
Further Information

Publication History

Publication Date:
17 September 2014 (online)

 

Significance

(+)-Cavicularin, isolated from the liverwort Cavicularia densa, is a chiral cyclophane natural product. Because of its unusual molecular structure, several total syntheses have been reported to date. Zhao and Beaudry report a conceptionally different approach, which relies on an intramolecular enantioselective pyrone Diels–Alder reaction with subsequent CO2 extrusion to generate the aromatic A ring of the natural product.


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Comment

The synthesis commences with a remarkably selective one-pot three-component ­Suzuki cross-coupling between dibromide B and boronic esters A and C. Coupling product D was further advanced to α-hydroxy pyrone E. In the presence of cinchona alkaloid F, this material underwent the desired Diels–Alder reaction to yield intermediate G, which immediately eliminated CO2 and phenylsufinic acid to generate H as a single regioisomer. Finally, reduction and protecting group removal yielded (+)-cavicularin in 7.3% overall yield.


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