Abstract:
In spite of considerable advances in indole alkaloid chemistry and biology, many targets of high biological significance have yet to be prepared, and further synthetic advances are needed, especially with regard to the development of short, SAR-amenable total syntheses.[1] We have developed new indole syntheses and applied them toward concise strategies toward ergot and macroline alkaloids, with the goal to accomplish a rapid assembly of core structures and thus enable iterative SAR investigations.
This presentation will focus on our strategic innovations in the total synthesis of indole alkaloids, in particular our recent work in the macroline/sarpagine/ajmaline class of natural products containing an indole-fused 9-azabicyclo[3.3.1]nonane (9-ABN) core structure.
[1] Tasker, N. R.; Wipf, P. Biosynthesis, Total Synthesis, and Biological Profiles of Ergot Alkaloids.
In: Knölker H-J, Editor. The Alkaloids: Chemistry and Biology: Academic Press; 2021, vol. 85, p.
1-112.
[2] Bohn, A. G.; Cipriano, B. M.; Tasker, N. R.; Wipf, P. “Asymmetric Synthesis of the 9-
Azabicyclo[3.3.1]nonane Core of Macroline-Type Alkaloids.” Synthesis 2026, 58(8), 926-938