Issue 31, 2024

Divergent total syntheses of pyrroloiminoquinone alkaloids enabled by the development of a Larock/Buchwald–Hartwig annulation/cyclization

Abstract

Pyrroloiminoquinone alkaloids are a large class of natural products that display a wide range of biological activities. Synthetic approaches to these natural products typically rely on a common late-stage C10-oxygenated pyrroloiminoquinone intermediate, but these strategies often lead to lengthy synthetic sequences that are not amenable to divergent syntheses. We devised an alternative approach aimed at the early introduction of the C10 nitrogen, which we hypothesized would enable late-stage diversification. This strategy hinged upon a Larock/Buchwald–Hartwig annulation/cyclization to quickly access the core of these alkaloids. We report the development of this cascade process, which was facilitated by a dual ligand system in addition to selective functionalization of the key intermediate, to provide efficient syntheses of makaluvamines A, C, and D and isobatzelline B, and the first total synthesis of makaluvamine N.

Graphical abstract: Divergent total syntheses of pyrroloiminoquinone alkaloids enabled by the development of a Larock/Buchwald–Hartwig annulation/cyclization

Supplementary files

Article information

Article type
Edge Article
Submitted
06 May 2024
Accepted
20 Jun 2024
First published
27 Jun 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, 12284-12290

Divergent total syntheses of pyrroloiminoquinone alkaloids enabled by the development of a Larock/Buchwald–Hartwig annulation/cyclization

S. P. Rezgui, J. Farhi, H. Yu, Z. P. Sercel, S. C. Virgil and B. M. Stoltz, Chem. Sci., 2024, 15, 12284 DOI: 10.1039/D4SC02981J

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