Download PDF
Synthesis
DOI: 10.1055/a-2779-1148
Paper

Asymmetric Synthesis of the 9-Azabicyclo[3.3.1]nonane Core of Macroline-Type Alkaloids

Authors

  • Ashlyn G. Bohn

    1   Department of Chemistry, University of Pittsburgh, Pittsburgh, United States (Ringgold ID: RIN6614)

  • Benjamin M. Cipriano

    1   Department of Chemistry, University of Pittsburgh, Pittsburgh, United States (Ringgold ID: RIN6614)

  • Nikhil R. Tasker

    1   Department of Chemistry, University of Pittsburgh, Pittsburgh, United States (Ringgold ID: RIN6614)

  • Peter Wipf

    1   Department of Chemistry, University of Pittsburgh, Pittsburgh, United States (Ringgold ID: RIN6614)

Supported by: National Institutes of Health
Further Information
 PDF Download All articles of this category

The signature indole-fused 9-azabicyclo[3.3.1]nonane (9-ABN) core of macroline-type alkaloids in its natural configuration has been accessed in 4 steps and 16% overall yield from 1H-indole and an L-menthyl nicotinate-derived pyridyl alcohol. The two starting fragments were condensed using a hydrogen auto-transfer (HA) strategy. The key stereocenter at C-5 was installed in up to 95:5 dr with a double diastereoselective, chiral auxiliary-assisted asymmetric transfer hydrogenation (CAATHy). The selective partial reduction of the pyridine to the tetrahydropyridine set the stage for a stereospecific formation of the bridged bicyclic 9-ABN system with a novel superacid-mediated cycloisomerization reaction. Starting from indole and 6-(hydroxymethyl)nicotinate esters, this new strategy provides a rapid, protecting group- and transition metal-free access to the tetracyclic macroline core.



Publication History

Received: 19 October 2025

Accepted after revision: 24 December 2025

Accepted Manuscript online:
25 December 2025

© . Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany