Bioinspired Total Synthesis of Bipolarolides A and B

Abstract

We have achieved the first total synthesis of bipolarolides A and B, which possess an intriguing and complex 5/6/6/6/5 caged pentacyclic skeleton with seven contiguous stereocenters. The synthesis features a lithium‐halogen exchange/intermolecular nucleophilic addition to link two enantioenriched fragments, two ring‐closing metathesis reactions to assemble the five‐ and eight‐membered rings, and a bioinspired Prins reaction/ether formation cascade cyclization to construct the 5/6/6/6/5 caged skeleton.

Concise Total Synthesis of (−)-Bipolarolide D

“…Recently, the first total syntheses of its congeners, bipolarolides A and B, have been accomplished by the Jia group. 14 Here we report the first enantioselective total synthesis of bipolarolide D (1).…”

“…While this compound’s unique structural features and biological properties of the ophiobolin family suggest potential avenues for future pharmacological research, − the scarcity of the source of 1 restricts in-depth research on its biological activity. Recently, the first total syntheses of its congeners, bipolarolides A and B, have been accomplished by the Jia group . Here we report the first enantioselective total synthesis of bipolarolide D ( 1 ).…”

Undobolins A–L, Ophiobolin-Type Sesterterpenoids from Aspergillus undulatus

“…Ophiobolin-type sesterterpenoids have received much attention from the synthetic and biosynthetic communities. Five total syntheses of ophiobolins have been developed in the past three decades. − (+)-Ophiobolin C was the first example, syntheszed by Kishi and co-workers in 38 steps in 1989, and Jia’s team accomplished the first total syntheses of bipolarolides A and B in 28 steps and 25 steps from (−)-citronellal …”