An Enantioselective Approach for the Structure Revision of Isolophanthin E and Syntheses of Proposed Structures of Isolophanthins A, B, and C

The first enantioselective total synthesis and structure revision of isolophanthin E and syntheses of proposed structures of isolophanthins A, B, and C are demonstrated. Natural product 3β-hydroxy-8,11,13,15-abietatetraene was directly synthesized utilizing an efficient cationic polyene cyclization, and it is used as a common intermediate in the synthesis of isolophanthins and related abietatriene natural products. Two distinct synthetic routes were established for the synthesis of different stereoisomers of isolophanthin E. Spectroscopic analysis and structural assignment of isolophanthin E stereoisomers provide valuable insights into the relative configuration of the C-2, C-3-dihydroxy A ring of similar terpenoids, aiding in the identification of their configuration. A total of seven diterpenoids were obtained using regioselective chloromethylation, Sharpless dihydroxylation, Cu(II) catalyzed allyl-benzyl coupling, epoxide-initiated polyene cyclization, Rubottom oxidation, and additive-controlled dihydroxylation as key synthetic steps.