Total Synthesis of (+)-Peniciketal A

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.

Publikationsverlauf

Artikel online veröffentlicht:
18. März 2021