Total Synthesis of (+)-Strongylin A, a Rearranged Sesquiterpenoid Hydroquinone from a Marine Sponge

A biologically attractive and structurally unique marine natural product, (+)‐strongylin A (1), was synthesized for the first time by starting from a known trans‐decalone derivative (19 % overall yield in 11 steps). The synthetic method involved the following key steps: (i) stereocontrolled hydrogenation of an exo‐olefinic decalin to install the C8 stereogenic centre present in the required decalin segment; (ii) coupling of the decalin segment with an aromatic moiety to assemble the desired carbon skeleton; and (iii) sequential BF3·Et2O‐induced dehydroxylation/rearrangement/cyclization of a decalin tertiary alcohol to directly produce target compound 1. This total synthesis has established the absolute configuration of the natural product. (+)‐Strongylin A has been synthesized for the first time by starting from (+)‐5‐methyl‐Wieland–Miescher ketone (16 % overall yield in 14 steps). The characteristic tetracyclic core structure was constructed in a domino dehydroxylation/rearrangement/cyclization reaction.