Synfacts 2021; 17(04): 0363
DOI: 10.1055/s-0040-1719433
Synthesis of Natural Products and Potential Drugs

Total Synthesis of (+)-Peniciketal A

Contributor(s):
Erick M. Carreira
,
Patrick Pfaff
Deng Y, Yang C.-PH, Smith III AB. * University of Pennsylvania, Philadelphia, USA
Enantioselective Total Synthesis of (+)-Peniciketals A and B: Two Architecturally Complex Spiroketals.

J. Am. Chem. Soc. 2021;
143: 1740-1744
DOI: 10.1021/jacs.0c11424.
 

Significance

Smith and co-workers report the first total synthesis of (+)-peniciketal A, a complex spiroketal isolated from fungus Penicillium raistrickii. The benzannulated [6,6]-spiroketal has been shown to possess activity against human cancer cell lines and might serve as a promising drug lead candidate.


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Comment

The authors employed a highly convergent approach that combines the two fragments F and G in a photoisomerization–cyclization cascade. Fragment F is generated from epoxide A by attack of dithiane B; Brook rearrangement then enables alkylation with D in a single pot. This is followed by selective silyl deprotection and in situ spiroketalization. Fragment G is obtained from ­atraric acid (H) via Negishi coupling and cross-­metathesis.


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Publication History

Publication Date:
18 March 2021 (online)

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