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Synthesis of β-Carbolines with Electrocyclic Cyclization of 3-Nitrovinylindoles
The β-carboline motif is common in drug discovery and among numerous biologically active natural products. However, its synthetic preparation relies on multistep sequences and heavily depends on the type of substitution required in the core of the desired β-carboline target. Herein, we demonstrate t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487476/ https://www.ncbi.nlm.nih.gov/pubmed/37685914 http://dx.doi.org/10.3390/ijms241713107 |
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author | Aksenov, Nicolai A. Arutiunov, Nikolai A. Aksenov, Alexander V. Kirilov, Nikita K. Aksenova, Inna V. Aksenov, Dmitrii A. Aleksandrova, Elena V. Rubin, Michael Kornienko, Alexander |
author_facet | Aksenov, Nicolai A. Arutiunov, Nikolai A. Aksenov, Alexander V. Kirilov, Nikita K. Aksenova, Inna V. Aksenov, Dmitrii A. Aleksandrova, Elena V. Rubin, Michael Kornienko, Alexander |
author_sort | Aksenov, Nicolai A. |
collection | PubMed |
description | The β-carboline motif is common in drug discovery and among numerous biologically active natural products. However, its synthetic preparation relies on multistep sequences and heavily depends on the type of substitution required in the core of the desired β-carboline target. Herein, we demonstrate that this structural motif can be accessed with the microwave-assisted electrocyclic cyclization of heterotrienic aci (alkylideneazinic acid) forms of 3-nitrovinylindoles. The reaction can start with 3-nitrovinylindoles themselves under two sets of conditions. The first one involves microwave irradiation of butanolic solutions of 3-nitrovinylindoles, whereas the second one consists of prior Boc protection of indolic nitrogen, where the protecting group cleanly comes off during the course of the reaction. Alternatively, the reaction can start with 3-nitrovinylindoles prepared in situ using various processes. Finally, the reaction may utilize indoles with β-nitrostyrenes, likely involving the intermediacy of spirocyclic oxazolines, which rearrange to similar heterotrienic systems undergoing cyclization to β-carbolines. As part of this study, several natural products, namely, alkaloids norharmane, harmane, and eudistomin N, were synthesized. |
format | Online Article Text |
id | pubmed-10487476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104874762023-09-09 Synthesis of β-Carbolines with Electrocyclic Cyclization of 3-Nitrovinylindoles Aksenov, Nicolai A. Arutiunov, Nikolai A. Aksenov, Alexander V. Kirilov, Nikita K. Aksenova, Inna V. Aksenov, Dmitrii A. Aleksandrova, Elena V. Rubin, Michael Kornienko, Alexander Int J Mol Sci Article The β-carboline motif is common in drug discovery and among numerous biologically active natural products. However, its synthetic preparation relies on multistep sequences and heavily depends on the type of substitution required in the core of the desired β-carboline target. Herein, we demonstrate that this structural motif can be accessed with the microwave-assisted electrocyclic cyclization of heterotrienic aci (alkylideneazinic acid) forms of 3-nitrovinylindoles. The reaction can start with 3-nitrovinylindoles themselves under two sets of conditions. The first one involves microwave irradiation of butanolic solutions of 3-nitrovinylindoles, whereas the second one consists of prior Boc protection of indolic nitrogen, where the protecting group cleanly comes off during the course of the reaction. Alternatively, the reaction can start with 3-nitrovinylindoles prepared in situ using various processes. Finally, the reaction may utilize indoles with β-nitrostyrenes, likely involving the intermediacy of spirocyclic oxazolines, which rearrange to similar heterotrienic systems undergoing cyclization to β-carbolines. As part of this study, several natural products, namely, alkaloids norharmane, harmane, and eudistomin N, were synthesized. MDPI 2023-08-23 /pmc/articles/PMC10487476/ /pubmed/37685914 http://dx.doi.org/10.3390/ijms241713107 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Aksenov, Nicolai A. Arutiunov, Nikolai A. Aksenov, Alexander V. Kirilov, Nikita K. Aksenova, Inna V. Aksenov, Dmitrii A. Aleksandrova, Elena V. Rubin, Michael Kornienko, Alexander Synthesis of β-Carbolines with Electrocyclic Cyclization of 3-Nitrovinylindoles |
title | Synthesis of β-Carbolines with Electrocyclic Cyclization of 3-Nitrovinylindoles |
title_full | Synthesis of β-Carbolines with Electrocyclic Cyclization of 3-Nitrovinylindoles |
title_fullStr | Synthesis of β-Carbolines with Electrocyclic Cyclization of 3-Nitrovinylindoles |
title_full_unstemmed | Synthesis of β-Carbolines with Electrocyclic Cyclization of 3-Nitrovinylindoles |
title_short | Synthesis of β-Carbolines with Electrocyclic Cyclization of 3-Nitrovinylindoles |
title_sort | synthesis of β-carbolines with electrocyclic cyclization of 3-nitrovinylindoles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487476/ https://www.ncbi.nlm.nih.gov/pubmed/37685914 http://dx.doi.org/10.3390/ijms241713107 |
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