Paquette LA,
*,
Geng F.
The Ohio State University, Columbus, USA
Applications of the Squarate Ester Cascade to the Expeditious Synthesis of Hypnophilin,
Coriolin, and Ceratopicanol.
J. Am. Chem. Soc. 2002;
124: 9199-9203
DOI:
10.1021/ja020474t
Key words
(±)-hypnophilin - triquinane - squarate ester - transannular aldol reaction - Birch
reduction - Saegusa oxidation - Weitz–Scheffer epoxidation
Significance
Paquette and Geng present the synthesis of (±)-hypnophilin. The linearly fused triquinane
was isolated in 1981 from the fungus Pleurotellues hypnophilus and exhibits antitumor, antibacterial, and antifungal activity. Key to the reported
synthesis is rapid assembly of the triquinane skeleton through a reaction cascade
from squarate ester addition product C.
Comment
Rearrangement of putative intermediate C, followed by transannular aldol reaction and hydrolysis, furnished triquinane F. Conversion to the β-chloro carbonyl and subsequent reduction under Birch conditions
produced secondary alcohol G. Saegusa oxidation of enone I, followed by Weitz–Scheffer epoxidation, completed the synthesis of (±)-hypnophilin.
