Pleurotin Total Synthesis: Legacy Route and Recent Progress

Pleurotin ( 1 ) is a meroterpenoid antibiotic isolated from basidiomycete fungi. This natural product possesses an unprecedented hexacyclic [6/6/6/5/5/7] fused‐ring architecture containing a thermodynamically disfavored tetrasubstituted trans ‐hydrindane CD ring system, linked to a benzoquinone A ring through a B‐ring bridge, together with eight contiguous stereogenic centers including a fully substituted quaternary carbon at C10. It exhibits potent inhibitory activity against the thioredoxin–thioredoxin reductase system (IC 50 = 170 nM), showing potential for antitumor drug development. The remarkable biological properties and challenging structural architecture of this molecule have established it as an exceptionally attractive synthetic target, inspiring long‐standing interest within the synthetic community. Consequently, extensive efforts have been devoted to the total synthesis of pleurotin ( 1 ). This review summarizes the racemic and enantioselective synthetic strategies, highlighting the longest linear sequence (LLS), overall yield, key steps, and ring construction sequences and compares the distinct features of different approaches.