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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7571100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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