Total Synthesis of\nthe Hexacyclic Sesterterpenoid\nNiduterpenoid B via Structural Reorganization Strategy

To date, it remains challenging to precisely and efficiently\nconstruct\nstructurally intriguing polycarbocycles with densely packed stereocenters\nin organic synthesis. Niduterpenoid B, a naturally occurring ERα\ninhibitor, exemplifies this complexity with its intricate polycyclic\nnetwork comprising 5 cyclopentane and 1 cyclopropane rings, featuring\n13 contiguous stereocenters, including 4 all-carbon quaternary centers.\nIn this work, we describe the first total synthesis of niduterpenoid\nB using a structural reorganization strategy. Key features include\nthe following: (1) an efficient methoxy-controlled cascade reaction\nthat precisely forges a highly functionalized tetraquinane (A–D\nrings) bearing sterically hindered contiguous quaternary stereocenters;\n(2) a rhodium-catalyzed [1 + 2] cycloaddition that facilitates the\nconstruction of a strained 3/5 bicycle (E–F rings) angularly\nfused with ring D.