Total Synthesis of Shearinines D and G: A Convergent Approach to Indole Diterpenoids

Abstract

The first total syntheses of the indole diterpenoids (+ +)-shearinine Ga nd Da re disclosed. The successful routes rely on late-stage coupling of two complex fragments.F ormation of the challenging trans-hydrindane motif was accomplished by diastereoselective,i ntramolecular cyclopropanation. Aone-pot sequence consisting of Sharpless dihydroxylation/Achmatowicz reaction was developed to install the dioxabicyclo[3.2.1]octane motif.T he indenone subunit was accessed by Prins cyclization. Tuning the electronic nature of the substituents on the parent arylcarboxaldehyde allowed access to divergent products that were further transformed into shearinines Ga nd D. Riley-type oxidation of abicyclic enone yielded as urprising stereochemical outcome.

Synthesis of Pyranocyclopentaindolines Representing the Western Sections of Janthitrem B, JBIR‐137, and Shearinine G

“…In this paper, we report on our experience with the synthesis of the ABCD tetracyclic substructure shared by janthitrem B (1), JBIR-137 (2), and shearinine G (3). Having achieved the synthesis of raputindole A and dihydroraputindole D employing gold(I) chemistry, [9] we chose to start from indoline (8). This approach differs from the Carreira route that assembled ring D after construction of the ABC tricycle.…”

“…This approach differs from the Carreira route that assembled ring D after construction of the ABC tricycle. [8] We pursued several strategies (Scheme 1).…”

“…Having achieved the synthesis of raputindole A and dihydroraputindole D employing gold(I) chemistry, [9] we chose to start from indoline ( 8 ). This approach differs from the Carreira route that assembled ring D after construction of the ABC tricycle [8] . We pursued several strategies (Scheme 1).…”

“…We invested some effort in the development of novel routes that could have assembled the tetrahydropyran ring as the final one of the four rings. As Carreira et al in their 2021 total synthesis of the shearinines D and G, [8] we had rely to the Prins cyclization of a dihydropyranyl-substituted aryl aldehyde first achieved by the Magnus group for benzaldehyde derivatives. However, such a Prins Scheme 6.…”

“…Until very recently, there was no total synthesis of the janthitrem‐type indole diterpenoids published. In 2021, Carreira and coworkers reported the total synthesis of shearinines G ( 3 ) and D [8] …”