Practical and Scalable Total Syntheses of (+)-Dysidavarones A-C

A practical and scalable enantioselective total syntheses of the marine anticancer sesquiterpene quinone meroterpenoids (+)-dysidavarones A-C has been accomplished. The central bridged bicyclo[3.3.1]nonane structure of dysidavarones was efficiently established by a one-pot intermolecular diastereoselective alkylation and intramoleculara-arylation of a Wieland-Miescher ketone derivative with a substituted benzylic bromide, without protection of the more-reactive C4 carbonyl group. (+)-Dysidavarones A and E' were prepared on a 150 mg scale, demonstrating the efficiency and reliability of our synthetic route and providing sufficient amounts of the dysidavarones for further bioactivity evaluation.