Bioinspired Total Synthesis of Bipolarolides A and B

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. The bioinspired total synthesis of bipolarolides A and B was achieved by using a lithium-halogen exchange/intermolecular nucleophilic addition to link two enantiomerically enriched 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.+image