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
Key words
(+)-peniciketal A - spiroketals - [1,4]-Brook rearrangement - spiroketalization - photoisomerization - cyclization
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.
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.
