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Functionalization of Betulinic Acid with Polyphenolic Fragments for the Development of New Amphiphilic Antioxidants

The present work aimed at the valorization of biomass derived compounds by their transformation into new added-value compounds with enhanced antioxidant properties. In this context, betulinic acid (BA) was decorated with polyphenolic fragments, and polyhydroxylated (E)-2-benzylidene-19,28-epoxyolean...

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Autores principales: Sousa, Joana L. C., Gonçalves, Cristiana, Ferreira, Ricardo M., Cardoso, Susana M., Freire, Carmen S. R., Silvestre, Armando J. D., Silva, Artur M. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909560/
https://www.ncbi.nlm.nih.gov/pubmed/33498465
http://dx.doi.org/10.3390/antiox10020148
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author Sousa, Joana L. C.
Gonçalves, Cristiana
Ferreira, Ricardo M.
Cardoso, Susana M.
Freire, Carmen S. R.
Silvestre, Armando J. D.
Silva, Artur M. S.
author_facet Sousa, Joana L. C.
Gonçalves, Cristiana
Ferreira, Ricardo M.
Cardoso, Susana M.
Freire, Carmen S. R.
Silvestre, Armando J. D.
Silva, Artur M. S.
author_sort Sousa, Joana L. C.
collection PubMed
description The present work aimed at the valorization of biomass derived compounds by their transformation into new added-value compounds with enhanced antioxidant properties. In this context, betulinic acid (BA) was decorated with polyphenolic fragments, and polyhydroxylated (E)-2-benzylidene-19,28-epoxyoleanane-3,28-diones 4a–d were obtained. For that, the synthetic strategy relied on base-promoted aldol condensation reactions of methyl betulonate, which was previously prepared from natural BA, with appropriate benzaldehydes, followed by cleavage of the methyl protecting groups with BBr(3). It is noteworthy that the HBr release during the work-up of the cleavage reactions led to the rearrangement of the lupane-type skeleton of the expected betulonic acid derivatives into oleanane-type compounds 4a–d. The synthesized compounds 4a–d were designed to have specific substitution patterns at C-2 of the triterpene scaffold, allowing the establishment of a structure-activity relationship. The radical scavenging ability of 4a–d was evaluated using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(•)) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS(•+)) scavenging assays. In particular, derivative 4c, bearing a catechol unit, revealed to be the most efficient scavenger against both free radicals DPPH(•) and ABTS(•+). Subsequently, we designed two analogues of the hit derivative 4c in order to achieve more potent antioxidant agents: (i) the first analogue carries an additional unsaturation in its lateral chain at C-2 (analogue 5) and (ii) in the second analogue, E-ring was kept in its open form (analogue 6). It was observed that the presence of an extended π-conjugated system at C-2 contributed to an increased scavenging effect, since analogue 5 was more active than 6, α-tocopherol, and 4c in the ABTS(•+) assay.
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spelling pubmed-79095602021-02-27 Functionalization of Betulinic Acid with Polyphenolic Fragments for the Development of New Amphiphilic Antioxidants Sousa, Joana L. C. Gonçalves, Cristiana Ferreira, Ricardo M. Cardoso, Susana M. Freire, Carmen S. R. Silvestre, Armando J. D. Silva, Artur M. S. Antioxidants (Basel) Article The present work aimed at the valorization of biomass derived compounds by their transformation into new added-value compounds with enhanced antioxidant properties. In this context, betulinic acid (BA) was decorated with polyphenolic fragments, and polyhydroxylated (E)-2-benzylidene-19,28-epoxyoleanane-3,28-diones 4a–d were obtained. For that, the synthetic strategy relied on base-promoted aldol condensation reactions of methyl betulonate, which was previously prepared from natural BA, with appropriate benzaldehydes, followed by cleavage of the methyl protecting groups with BBr(3). It is noteworthy that the HBr release during the work-up of the cleavage reactions led to the rearrangement of the lupane-type skeleton of the expected betulonic acid derivatives into oleanane-type compounds 4a–d. The synthesized compounds 4a–d were designed to have specific substitution patterns at C-2 of the triterpene scaffold, allowing the establishment of a structure-activity relationship. The radical scavenging ability of 4a–d was evaluated using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(•)) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS(•+)) scavenging assays. In particular, derivative 4c, bearing a catechol unit, revealed to be the most efficient scavenger against both free radicals DPPH(•) and ABTS(•+). Subsequently, we designed two analogues of the hit derivative 4c in order to achieve more potent antioxidant agents: (i) the first analogue carries an additional unsaturation in its lateral chain at C-2 (analogue 5) and (ii) in the second analogue, E-ring was kept in its open form (analogue 6). It was observed that the presence of an extended π-conjugated system at C-2 contributed to an increased scavenging effect, since analogue 5 was more active than 6, α-tocopherol, and 4c in the ABTS(•+) assay. MDPI 2021-01-20 /pmc/articles/PMC7909560/ /pubmed/33498465 http://dx.doi.org/10.3390/antiox10020148 Text en © 2021 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
Sousa, Joana L. C.
Gonçalves, Cristiana
Ferreira, Ricardo M.
Cardoso, Susana M.
Freire, Carmen S. R.
Silvestre, Armando J. D.
Silva, Artur M. S.
Functionalization of Betulinic Acid with Polyphenolic Fragments for the Development of New Amphiphilic Antioxidants
title Functionalization of Betulinic Acid with Polyphenolic Fragments for the Development of New Amphiphilic Antioxidants
title_full Functionalization of Betulinic Acid with Polyphenolic Fragments for the Development of New Amphiphilic Antioxidants
title_fullStr Functionalization of Betulinic Acid with Polyphenolic Fragments for the Development of New Amphiphilic Antioxidants
title_full_unstemmed Functionalization of Betulinic Acid with Polyphenolic Fragments for the Development of New Amphiphilic Antioxidants
title_short Functionalization of Betulinic Acid with Polyphenolic Fragments for the Development of New Amphiphilic Antioxidants
title_sort functionalization of betulinic acid with polyphenolic fragments for the development of new amphiphilic antioxidants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909560/
https://www.ncbi.nlm.nih.gov/pubmed/33498465
http://dx.doi.org/10.3390/antiox10020148
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