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Synthetic- and DFT modelling studies on regioselective modified Mannich reactions of hydroxy-KYNA derivatives
The syntheses of hydroxy-substituted kynurenic acid (KYNA) derivatives have been achieved by an optimised Conrad–Limpach procedure. The derivatives were then reacted with morpholine and paraformaldehyde, as a representative amine and aldehyde, in a modified Mannich reaction. The newly introduced sub...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691111/ https://www.ncbi.nlm.nih.gov/pubmed/35423050 http://dx.doi.org/10.1039/d0ra08325a |
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author | Lőrinczi, Bálint Csámpai, Antal Fülöp, Ferenc Szatmári, István |
author_facet | Lőrinczi, Bálint Csámpai, Antal Fülöp, Ferenc Szatmári, István |
author_sort | Lőrinczi, Bálint |
collection | PubMed |
description | The syntheses of hydroxy-substituted kynurenic acid (KYNA) derivatives have been achieved by an optimised Conrad–Limpach procedure. The derivatives were then reacted with morpholine and paraformaldehyde, as a representative amine and aldehyde, in a modified Mannich reaction. The newly introduced substituents altered the preferred reaction centre of the KYNA skeleton. A systematic investigation of substitutions was carried out, using different reaction conditions, resulting in mono- or disubstituted derivatives. Product selectivity and regioselectivity were rationalised by DFT calculations disclosing HOMO distribution and NBO charges on the potential nucleophilic centres in the anion of the appropriate KYNA ester assumed to be active components towards the iminium ion intermediate. |
format | Online Article Text |
id | pubmed-8691111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-86911112022-04-13 Synthetic- and DFT modelling studies on regioselective modified Mannich reactions of hydroxy-KYNA derivatives Lőrinczi, Bálint Csámpai, Antal Fülöp, Ferenc Szatmári, István RSC Adv Chemistry The syntheses of hydroxy-substituted kynurenic acid (KYNA) derivatives have been achieved by an optimised Conrad–Limpach procedure. The derivatives were then reacted with morpholine and paraformaldehyde, as a representative amine and aldehyde, in a modified Mannich reaction. The newly introduced substituents altered the preferred reaction centre of the KYNA skeleton. A systematic investigation of substitutions was carried out, using different reaction conditions, resulting in mono- or disubstituted derivatives. Product selectivity and regioselectivity were rationalised by DFT calculations disclosing HOMO distribution and NBO charges on the potential nucleophilic centres in the anion of the appropriate KYNA ester assumed to be active components towards the iminium ion intermediate. The Royal Society of Chemistry 2020-12-24 /pmc/articles/PMC8691111/ /pubmed/35423050 http://dx.doi.org/10.1039/d0ra08325a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Lőrinczi, Bálint Csámpai, Antal Fülöp, Ferenc Szatmári, István Synthetic- and DFT modelling studies on regioselective modified Mannich reactions of hydroxy-KYNA derivatives |
title | Synthetic- and DFT modelling studies on regioselective modified Mannich reactions of hydroxy-KYNA derivatives |
title_full | Synthetic- and DFT modelling studies on regioselective modified Mannich reactions of hydroxy-KYNA derivatives |
title_fullStr | Synthetic- and DFT modelling studies on regioselective modified Mannich reactions of hydroxy-KYNA derivatives |
title_full_unstemmed | Synthetic- and DFT modelling studies on regioselective modified Mannich reactions of hydroxy-KYNA derivatives |
title_short | Synthetic- and DFT modelling studies on regioselective modified Mannich reactions of hydroxy-KYNA derivatives |
title_sort | synthetic- and dft modelling studies on regioselective modified mannich reactions of hydroxy-kyna derivatives |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691111/ https://www.ncbi.nlm.nih.gov/pubmed/35423050 http://dx.doi.org/10.1039/d0ra08325a |
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