Synthetic Study Of Structurally Complex Indole Terpenes Total Syntheses Of (─)-Nodulisporic Acid D And (─)-Nodulisporic Acid C In Conjunction With Advanced Synthetic Studies Towards (+)-Nodulisporic Acid A And (─)-Nodulisporic Acid B

The first total syntheses of architecturally complex indole terpenes (−)-nodulisporic acid D and (−)-nodulisporic acid C are reported here via a unified strategy of late-stage union of large fragments. Key synthetic transformations in the total synthesis of (−)-nodulisporic acid D comprise vicinal difunctionalization of an advanced alpha,beta-unsaturated aldehyde to form the trans-fused 5,6-ring system in the eastern hemisphere and a palladium mediated cascade cross-coupling/indolization protocol leading to a multi-substituted indole core. Key synthetic transformations in the total synthesis of (−)-nodulisporic acid C venture include a Nozaki-Hiyama-Kishi reaction leading to a tricyclic western hemisphere intermediate, a late stage tert-butyl carbamate directed ortho-lithiation/prenylation, and a palladium catalyzed cascade cross coupling/indole formation.