Cargando…

Facile Amidation of Non-Protected Hydroxycinnamic Acids for the Synthesis of Natural Phenol Amides

Phenol amides are bioactive compounds naturally present in many plants. This class of compounds is known for antioxidant, anti-inflammatory, and anticancer activities. To better understand the reactivity and structure–bioactivity relationships of phenol amides, a large set of structurally diverse pu...

Descripción completa

Detalles Bibliográficos
Autores principales: van Zadelhoff, Annemiek, Vincken, Jean-Paul, de Bruijn, Wouter J. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000787/
https://www.ncbi.nlm.nih.gov/pubmed/35408599
http://dx.doi.org/10.3390/molecules27072203
_version_ 1784685521322115072
author van Zadelhoff, Annemiek
Vincken, Jean-Paul
de Bruijn, Wouter J. C.
author_facet van Zadelhoff, Annemiek
Vincken, Jean-Paul
de Bruijn, Wouter J. C.
author_sort van Zadelhoff, Annemiek
collection PubMed
description Phenol amides are bioactive compounds naturally present in many plants. This class of compounds is known for antioxidant, anti-inflammatory, and anticancer activities. To better understand the reactivity and structure–bioactivity relationships of phenol amides, a large set of structurally diverse pure compounds are needed, however purification from plants is inefficient and laborious. Existing syntheses require multiple steps, including protection of functional groups and are generally overly complicated and only suitable for specific combinations of hydroxycinnamic acid and amine. Thus, to facilitate further studies on these promising compounds, we aimed to develop a facile general synthetic route to obtain phenol amides with a wide structural diversity. The result is a protocol for straightforward one-pot synthesis of phenol amides at room temperature within 25 h using equimolar amounts of N,N′-dicyclohexylcarbodiimide (DCC), amine, hydroxycinnamic acid, and sodium bicarbonate in aqueous acetone. Eight structurally diverse phenol amides were synthesized and fully chemically characterized. The facile synthetic route described in this work is suitable for a wide variety of biologically relevant phenol amides, consisting of different hydroxycinnamic acid subunits (coumaric acid, ferulic acid, and sinapic acid) and amine subunits (agmatine, anthranilic acid, putrescine, serotonin, tyramine, and tryptamine) with yields ranging between 14% and 24%.
format Online
Article
Text
id pubmed-9000787
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90007872022-04-12 Facile Amidation of Non-Protected Hydroxycinnamic Acids for the Synthesis of Natural Phenol Amides van Zadelhoff, Annemiek Vincken, Jean-Paul de Bruijn, Wouter J. C. Molecules Communication Phenol amides are bioactive compounds naturally present in many plants. This class of compounds is known for antioxidant, anti-inflammatory, and anticancer activities. To better understand the reactivity and structure–bioactivity relationships of phenol amides, a large set of structurally diverse pure compounds are needed, however purification from plants is inefficient and laborious. Existing syntheses require multiple steps, including protection of functional groups and are generally overly complicated and only suitable for specific combinations of hydroxycinnamic acid and amine. Thus, to facilitate further studies on these promising compounds, we aimed to develop a facile general synthetic route to obtain phenol amides with a wide structural diversity. The result is a protocol for straightforward one-pot synthesis of phenol amides at room temperature within 25 h using equimolar amounts of N,N′-dicyclohexylcarbodiimide (DCC), amine, hydroxycinnamic acid, and sodium bicarbonate in aqueous acetone. Eight structurally diverse phenol amides were synthesized and fully chemically characterized. The facile synthetic route described in this work is suitable for a wide variety of biologically relevant phenol amides, consisting of different hydroxycinnamic acid subunits (coumaric acid, ferulic acid, and sinapic acid) and amine subunits (agmatine, anthranilic acid, putrescine, serotonin, tyramine, and tryptamine) with yields ranging between 14% and 24%. MDPI 2022-03-28 /pmc/articles/PMC9000787/ /pubmed/35408599 http://dx.doi.org/10.3390/molecules27072203 Text en © 2022 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 Communication
van Zadelhoff, Annemiek
Vincken, Jean-Paul
de Bruijn, Wouter J. C.
Facile Amidation of Non-Protected Hydroxycinnamic Acids for the Synthesis of Natural Phenol Amides
title Facile Amidation of Non-Protected Hydroxycinnamic Acids for the Synthesis of Natural Phenol Amides
title_full Facile Amidation of Non-Protected Hydroxycinnamic Acids for the Synthesis of Natural Phenol Amides
title_fullStr Facile Amidation of Non-Protected Hydroxycinnamic Acids for the Synthesis of Natural Phenol Amides
title_full_unstemmed Facile Amidation of Non-Protected Hydroxycinnamic Acids for the Synthesis of Natural Phenol Amides
title_short Facile Amidation of Non-Protected Hydroxycinnamic Acids for the Synthesis of Natural Phenol Amides
title_sort facile amidation of non-protected hydroxycinnamic acids for the synthesis of natural phenol amides
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000787/
https://www.ncbi.nlm.nih.gov/pubmed/35408599
http://dx.doi.org/10.3390/molecules27072203
work_keys_str_mv AT vanzadelhoffannemiek facileamidationofnonprotectedhydroxycinnamicacidsforthesynthesisofnaturalphenolamides
AT vinckenjeanpaul facileamidationofnonprotectedhydroxycinnamicacidsforthesynthesisofnaturalphenolamides
AT debruijnwouterjc facileamidationofnonprotectedhydroxycinnamicacidsforthesynthesisofnaturalphenolamides