Issue 15, 2024

Aza-Achmatowicz rearrangement coupled with intermolecular aza-Friedel–Crafts enables total syntheses of uleine and aspidosperma alkaloids

Abstract

Aspidosperma and uleine alkaloids belong to the large family of monoterpene indole alkaloids with diverse biological activities and thus have attracted extensive synthetic interest. Reported is the development of a new synthetic strategy that allows direct C3–C2′ linkage of indoles with functionalized 2-hydroxypiperidines to construct the core common to all aspidoserma and uleine alkaloids. Such indole-piperidine linkage is enabled by coupling aza-Achmatowicz rearrangement (AAR) with indoles via an intermolecular aza-Friedel–Crafts (iAFC) reaction. This AAR-iAFC reaction proceeds under mild acidic conditions with wide tolerance of functional groups (33 examples). The synthetic application of the AAR-iAFC method was demonstrated with collective total syntheses of 3 uleine-type and 6 aspidosperma alkaloids: (+)-3-epi-N-nor-dasycarpidone, (+)-3-epi-dasycarpidone, (+)-3-epi-uleine, 1,2-didehydropseudoaspidospermidine, 1,2-dehydroaspidospermidine, vincadifformine, winchinine B, aspidospermidine, and N-acetylaspidospermidine. We expect that this AAR-iAFC strategy is applicable to other monoterpene indole alkaloids with the C3–C2′ linkage of indoles and piperidines.

Graphical abstract: Aza-Achmatowicz rearrangement coupled with intermolecular aza-Friedel–Crafts enables total syntheses of uleine and aspidosperma alkaloids

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Article information

Article type
Edge Article
Submitted
25 Jan 2024
Accepted
11 Mar 2024
First published
14 Mar 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2024,15, 5730-5737

Aza-Achmatowicz rearrangement coupled with intermolecular aza-Friedel–Crafts enables total syntheses of uleine and aspidosperma alkaloids

F. Ma, Y. Li, K. Akkarasereenon, H. Qiu, Y. T. Cheung, Z. Guo and R. Tong, Chem. Sci., 2024, 15, 5730 DOI: 10.1039/D4SC00601A

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