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Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles

Herein, we report the successful syntheses of scarcely represented indole-based heterocycles which have a structural connection with biologically active natural-like molecules. The selective oxidation of indoline nucleus to indole, hydrolysis of ester and carbamoyl residues followed by decarboxylati...

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Autores principales: Ciccolini, Cecilia, De Crescentini, Lucia, Mantellini, Fabio, Mari, Giacomo, Santeusanio, Stefania, Favi, Gianfranco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571100/
https://www.ncbi.nlm.nih.gov/pubmed/32916997
http://dx.doi.org/10.3390/molecules25184124
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author Ciccolini, Cecilia
De Crescentini, Lucia
Mantellini, Fabio
Mari, Giacomo
Santeusanio, Stefania
Favi, Gianfranco
author_facet Ciccolini, Cecilia
De Crescentini, Lucia
Mantellini, Fabio
Mari, Giacomo
Santeusanio, Stefania
Favi, Gianfranco
author_sort Ciccolini, Cecilia
collection PubMed
description Herein, we report the successful syntheses of scarcely represented indole-based heterocycles which have a structural connection with biologically active natural-like molecules. The selective oxidation of indoline nucleus to indole, hydrolysis of ester and carbamoyl residues followed by decarboxylation with concomitant aromatization of the pyridazine ring starting from tetrahydro-1H-pyridazino[3,4-b]indole derivatives lead to fused indole-pyridazine compounds. On the other hand, non-fused indole-pyrazol-5-one scaffolds are easily prepared by subjecting the same C2,C3-fused indoline tetrahydropyridazines to treatment with trifluoroacetic acid (TFA). These methods feature mild conditions, easy operation, high yields in most cases avoiding the chromatographic purification, and broad substrate scope. Interestingly, the formation of indole linked pyrazol-5-one system serves as a good example of the application of the umpolung strategy in the synthesis of C3-alkylated indoles.
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spelling pubmed-75711002020-10-28 Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles Ciccolini, Cecilia De Crescentini, Lucia Mantellini, Fabio Mari, Giacomo Santeusanio, Stefania Favi, Gianfranco Molecules Article Herein, we report the successful syntheses of scarcely represented indole-based heterocycles which have a structural connection with biologically active natural-like molecules. The selective oxidation of indoline nucleus to indole, hydrolysis of ester and carbamoyl residues followed by decarboxylation with concomitant aromatization of the pyridazine ring starting from tetrahydro-1H-pyridazino[3,4-b]indole derivatives lead to fused indole-pyridazine compounds. On the other hand, non-fused indole-pyrazol-5-one scaffolds are easily prepared by subjecting the same C2,C3-fused indoline tetrahydropyridazines to treatment with trifluoroacetic acid (TFA). These methods feature mild conditions, easy operation, high yields in most cases avoiding the chromatographic purification, and broad substrate scope. Interestingly, the formation of indole linked pyrazol-5-one system serves as a good example of the application of the umpolung strategy in the synthesis of C3-alkylated indoles. MDPI 2020-09-09 /pmc/articles/PMC7571100/ /pubmed/32916997 http://dx.doi.org/10.3390/molecules25184124 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ciccolini, Cecilia
De Crescentini, Lucia
Mantellini, Fabio
Mari, Giacomo
Santeusanio, Stefania
Favi, Gianfranco
Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles
title Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles
title_full Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles
title_fullStr Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles
title_full_unstemmed Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles
title_short Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles
title_sort construction of unusual indole-based heterocycles from tetrahydro-1h-pyridazino[3,4-b]indoles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571100/
https://www.ncbi.nlm.nih.gov/pubmed/32916997
http://dx.doi.org/10.3390/molecules25184124
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