Tropane and related alkaloid skeletons via a radical [3+3]-annulation process

Tropanes and related bicyclic alkaloids are highly attractive compounds possessing a broad biological activity. Here we report a mild and simple protocol for the synthesis of N-arylated 8-azabicyclo[3.2.1]octane and 9-azabicyclo[3.3.1]nonane derivatives. It provides these valuable bicyclic alkaloid...

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Autores principales: Colson, Eloïse, Andrez, Julie, Dabbous, Ali, Dénès, Fabrice, Maurel, Vincent, Mouesca, Jean-Marie, Renaud, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814087/
https://www.ncbi.nlm.nih.gov/pubmed/36697883
http://dx.doi.org/10.1038/s42004-022-00671-x
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author Colson, Eloïse
Andrez, Julie
Dabbous, Ali
Dénès, Fabrice
Maurel, Vincent
Mouesca, Jean-Marie
Renaud, Philippe
author_facet Colson, Eloïse
Andrez, Julie
Dabbous, Ali
Dénès, Fabrice
Maurel, Vincent
Mouesca, Jean-Marie
Renaud, Philippe
author_sort Colson, Eloïse
collection PubMed
description Tropanes and related bicyclic alkaloids are highly attractive compounds possessing a broad biological activity. Here we report a mild and simple protocol for the synthesis of N-arylated 8-azabicyclo[3.2.1]octane and 9-azabicyclo[3.3.1]nonane derivatives. It provides these valuable bicyclic alkaloid skeletons in good yields and high levels of diastereoselectivity from simple and readily available starting materials using visible-light photoredox catalysis. These bicyclic aniline derivatives are hardly accessible via the classical Robinson tropane synthesis and represent a particularly attractive scaffold for medicinal chemistry. This unprecedented annulation process takes advantage of the unique reactivity of ethyl 2-(acetoxymethyl)acrylate as a 1,3-bis radical acceptor and of cyclic N,N-dialkylanilines as radical 1,3-bis radical donors. The success of this process relies on efficient electron transfer processes and highly selective deprotonation of aminium radical cations leading to the key α-amino radical intermediates.
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spelling pubmed-98140872023-01-10 Tropane and related alkaloid skeletons via a radical [3+3]-annulation process Colson, Eloïse Andrez, Julie Dabbous, Ali Dénès, Fabrice Maurel, Vincent Mouesca, Jean-Marie Renaud, Philippe Commun Chem Article Tropanes and related bicyclic alkaloids are highly attractive compounds possessing a broad biological activity. Here we report a mild and simple protocol for the synthesis of N-arylated 8-azabicyclo[3.2.1]octane and 9-azabicyclo[3.3.1]nonane derivatives. It provides these valuable bicyclic alkaloid skeletons in good yields and high levels of diastereoselectivity from simple and readily available starting materials using visible-light photoredox catalysis. These bicyclic aniline derivatives are hardly accessible via the classical Robinson tropane synthesis and represent a particularly attractive scaffold for medicinal chemistry. This unprecedented annulation process takes advantage of the unique reactivity of ethyl 2-(acetoxymethyl)acrylate as a 1,3-bis radical acceptor and of cyclic N,N-dialkylanilines as radical 1,3-bis radical donors. The success of this process relies on efficient electron transfer processes and highly selective deprotonation of aminium radical cations leading to the key α-amino radical intermediates. Nature Publishing Group UK 2022-04-28 /pmc/articles/PMC9814087/ /pubmed/36697883 http://dx.doi.org/10.1038/s42004-022-00671-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Colson, Eloïse
Andrez, Julie
Dabbous, Ali
Dénès, Fabrice
Maurel, Vincent
Mouesca, Jean-Marie
Renaud, Philippe
Tropane and related alkaloid skeletons via a radical [3+3]-annulation process
title Tropane and related alkaloid skeletons via a radical [3+3]-annulation process
title_full Tropane and related alkaloid skeletons via a radical [3+3]-annulation process
title_fullStr Tropane and related alkaloid skeletons via a radical [3+3]-annulation process
title_full_unstemmed Tropane and related alkaloid skeletons via a radical [3+3]-annulation process
title_short Tropane and related alkaloid skeletons via a radical [3+3]-annulation process
title_sort tropane and related alkaloid skeletons via a radical [3+3]-annulation process
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814087/
https://www.ncbi.nlm.nih.gov/pubmed/36697883
http://dx.doi.org/10.1038/s42004-022-00671-x
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