Enantioselective Total Synthesis of (−)-Limaspermidine and (−)-Kopsinine by a Nitroaryl Transfer Cascade Strategy

Brendan Horst; Daniël S. Verdoorn; Sven Hennig; Gydo van der Heijden; Eelco Ruijter

doi:10.1002/anie.202210592

Enantioselective Total Synthesis of (−)-Limaspermidine and (−)-Kopsinine by a Nitroaryl Transfer Cascade Strategy

Brendan Horst, Daniël S. Verdoorn, Sven Hennig, Gydo van der Heijden, Eelco Ruijter^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

We report an intramolecular conjugate addition/Truce-Smiles/E1cb cascade of 2-nitrobenzenesulfonamide-functionalized cyclohexenones as a new entry to the core scaffold of monoterpene indole alkaloids. The method was applied to the asymmetric total synthesis of (−)-limaspermidine, (−)-kopsinilam, and (−)-kopsinine, as well as the framework of the kopsifoline alkaloids, thus highlighting its complementarity to existing approaches involving the use of indole-based starting materials or the interrupted Fischer indole synthesis. Furthermore, we show that the cascade tolerates various substituents on the nitroarene, opening the way to other natural products as well as non-natural analogues.

Original language	English
Article number	e202210592
Number of pages	6
Journal	Angewandte Chemie. International Edition
Volume	61
Issue number	42
Early online date	25 Aug 2022
DOIs	https://doi.org/10.1002/anie.202210592
Publication status	Published - 17 Oct 2022

Bibliographical note

Funding Information:
This work was funded by the Dutch Research Council (NWO). We kindly acknowledge Elwin Janssen for NMR measurements, Daniel Preschel for HRMS measurements, and Dr. Jasper Biemolt and Marushka Tirion for experimental work (all VUA). Dr. Christophe M. L. Vande Velde (University of Antwerp) is gratefully acknowledged for advice in solving the crystal structure.

Publisher Copyright:
© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

Funding

This work was funded by the Dutch Research Council (NWO). We kindly acknowledge Elwin Janssen for NMR measurements, Daniel Preschel for HRMS measurements, and Dr. Jasper Biemolt and Marushka Tirion for experimental work (all VUA). Dr. Christophe M. L. Vande Velde (University of Antwerp) is gratefully acknowledged for advice in solving the crystal structure.

Funders	Funder number
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Universiteit Antwerpen

Keywords

Alkaloids
Asymmetric Synthesis
Domino Reactions
Total Synthesis

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10.1002/anie.202210592

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title = "Enantioselective Total Synthesis of (−)-Limaspermidine and (−)-Kopsinine by a Nitroaryl Transfer Cascade Strategy",

abstract = "We report an intramolecular conjugate addition/Truce-Smiles/E1cb cascade of 2-nitrobenzenesulfonamide-functionalized cyclohexenones as a new entry to the core scaffold of monoterpene indole alkaloids. The method was applied to the asymmetric total synthesis of (−)-limaspermidine, (−)-kopsinilam, and (−)-kopsinine, as well as the framework of the kopsifoline alkaloids, thus highlighting its complementarity to existing approaches involving the use of indole-based starting materials or the interrupted Fischer indole synthesis. Furthermore, we show that the cascade tolerates various substituents on the nitroarene, opening the way to other natural products as well as non-natural analogues.",

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note = "Funding Information: This work was funded by the Dutch Research Council (NWO). We kindly acknowledge Elwin Janssen for NMR measurements, Daniel Preschel for HRMS measurements, and Dr. Jasper Biemolt and Marushka Tirion for experimental work (all VUA). Dr. Christophe M. L. Vande Velde (University of Antwerp) is gratefully acknowledged for advice in solving the crystal structure. Publisher Copyright: {\textcopyright} 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",

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AU - van der Heijden, Gydo

AU - Ruijter, Eelco

N1 - Funding Information: This work was funded by the Dutch Research Council (NWO). We kindly acknowledge Elwin Janssen for NMR measurements, Daniel Preschel for HRMS measurements, and Dr. Jasper Biemolt and Marushka Tirion for experimental work (all VUA). Dr. Christophe M. L. Vande Velde (University of Antwerp) is gratefully acknowledged for advice in solving the crystal structure. Publisher Copyright: © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

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Enantioselective Total Synthesis of (−)-Limaspermidine and (−)-Kopsinine by a Nitroaryl Transfer Cascade Strategy

Abstract

Bibliographical note

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Keywords

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CCDC 2180883: Experimental Crystal Structure Determination

Cite this

Enantioselective Total Synthesis of (−)-Limaspermidine and (−)-Kopsinine by a Nitroaryl Transfer Cascade Strategy

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

Datasets

CCDC 2180883: Experimental Crystal Structure Determination

Cite this