Total Synthesis of (–)-Bipolarolide D

Key words

(–)-bipolarolide D - enantioselective [6+2] cycloaddition - Heck reaction - Rh-catalyzed isomerization - Grignard addition - Babler–Dauben oxidation - Suzuki reaction

Significance

Lu and co-workers report the first total synthesis of the sesterpenoid (–)-bipolarolide D. The natural product, which was isolated from the fungus Bipolaris sp. TJ403-B1, is biosynthetically related to the ophiobolin class. The synthesis of the natural product with its 5/5/5/5-tetracyclic skeleton and three contiguous quaternary centers hinges on enantioselective [6+2] cycloaddition, enolate alkylation, and Heck reaction.

Comment

Pentafulvene aldehyde A was converted into ketone C by enantioselective [6+2] cycloaddition and ketal hydrolysis. Alkylation followed by Heck reaction and hydrolysis gave rise to triene G. Installation of the side chain from diketone J was achieved through Grignard addition and Suzuki reaction, furnishing the pentacyclic hemiketal N. Elimination followed by global deprotection afforded (–)-bipolarolide D.

Publication History

Article published online:
25 July 2024