Synthesis of Novel Bioactive Lipophilic Hydroxyalkyl Esters and Diesters Based on Hydroxyphenylacetic Acids

Novel lipophilic hydroxyalkyl esters were synthetized by Fischer esterification in good to excellent yields (60–96%) from a panel of hydroxyphenylacetic acids and increasing chain length (2 to 8 carbon atoms) α,ω-diols. The in vitro antioxidant activity of these compounds was evaluated by DPPH and A...

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Main Authors: Andrea Fochetti, Noemi Villanova, Andrea Lombardi, Veronica Lelli, Yuri Gazzilli, Anna Maria Timperio, Giancarlo Fabrizi, Roberta Bernini
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/15/3087
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author Andrea Fochetti
Noemi Villanova
Andrea Lombardi
Veronica Lelli
Yuri Gazzilli
Anna Maria Timperio
Giancarlo Fabrizi
Roberta Bernini
author_facet Andrea Fochetti
Noemi Villanova
Andrea Lombardi
Veronica Lelli
Yuri Gazzilli
Anna Maria Timperio
Giancarlo Fabrizi
Roberta Bernini
author_sort Andrea Fochetti
collection DOAJ
description Novel lipophilic hydroxyalkyl esters were synthetized by Fischer esterification in good to excellent yields (60–96%) from a panel of hydroxyphenylacetic acids and increasing chain length (2 to 8 carbon atoms) α,ω-diols. The in vitro antioxidant activity of these compounds was evaluated by DPPH and ABTS assays. Hydroxybutyl esters and hydroxyphenylacetic acids were used as starting materials for the synthesis of novel lipophilic diesters (butyl diarylacetates) using Mitsunobu reaction. The final products were isolated in moderate to good yields (40–78%), and their structure–antioxidant activity relationships are discussed. Compounds bearing the catechol moiety on one of the two aromatic rings and high lipophilicity proved to be the strongest antioxidants and were selected for testing as antibacterials against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>, obtaining preliminary and promising results.
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series Molecules
spelling doaj-art-e282d3eff54d4b0b850a59de3e876cc42025-08-20T03:36:27ZengMDPI AGMolecules1420-30492025-07-013015308710.3390/molecules30153087Synthesis of Novel Bioactive Lipophilic Hydroxyalkyl Esters and Diesters Based on Hydroxyphenylacetic AcidsAndrea Fochetti0Noemi Villanova1Andrea Lombardi2Veronica Lelli3Yuri Gazzilli4Anna Maria Timperio5Giancarlo Fabrizi6Roberta Bernini7Department of Agriculture and Forest Sciences (DAFNE), University of Tuscia, Via San Camillo de Lellis, 01100 Viterbo, ItalyDepartment of Agriculture and Forest Sciences (DAFNE), University of Tuscia, Via San Camillo de Lellis, 01100 Viterbo, ItalyDepartment of Agriculture and Forest Sciences (DAFNE), University of Tuscia, Via San Camillo de Lellis, 01100 Viterbo, ItalyDepartment of Ecological and Biological Sciences (DEB), University of Tuscia, 01100 Viterbo, ItalyDepartment of Chemistry and Technology of Drugs, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Ecological and Biological Sciences (DEB), University of Tuscia, 01100 Viterbo, ItalyDepartment of Chemistry and Technology of Drugs, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Agriculture and Forest Sciences (DAFNE), University of Tuscia, Via San Camillo de Lellis, 01100 Viterbo, ItalyNovel lipophilic hydroxyalkyl esters were synthetized by Fischer esterification in good to excellent yields (60–96%) from a panel of hydroxyphenylacetic acids and increasing chain length (2 to 8 carbon atoms) α,ω-diols. The in vitro antioxidant activity of these compounds was evaluated by DPPH and ABTS assays. Hydroxybutyl esters and hydroxyphenylacetic acids were used as starting materials for the synthesis of novel lipophilic diesters (butyl diarylacetates) using Mitsunobu reaction. The final products were isolated in moderate to good yields (40–78%), and their structure–antioxidant activity relationships are discussed. Compounds bearing the catechol moiety on one of the two aromatic rings and high lipophilicity proved to be the strongest antioxidants and were selected for testing as antibacterials against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>, obtaining preliminary and promising results.https://www.mdpi.com/1420-3049/30/15/3087hydroxyphenylacetic acidshydroxyalkyl estersbutyl diarylacetateslipophilicityantioxidant activityDPPH assay
spellingShingle Andrea Fochetti
Noemi Villanova
Andrea Lombardi
Veronica Lelli
Yuri Gazzilli
Anna Maria Timperio
Giancarlo Fabrizi
Roberta Bernini
Synthesis of Novel Bioactive Lipophilic Hydroxyalkyl Esters and Diesters Based on Hydroxyphenylacetic Acids
Molecules
hydroxyphenylacetic acids
hydroxyalkyl esters
butyl diarylacetates
lipophilicity
antioxidant activity
DPPH assay
title Synthesis of Novel Bioactive Lipophilic Hydroxyalkyl Esters and Diesters Based on Hydroxyphenylacetic Acids
title_full Synthesis of Novel Bioactive Lipophilic Hydroxyalkyl Esters and Diesters Based on Hydroxyphenylacetic Acids
title_fullStr Synthesis of Novel Bioactive Lipophilic Hydroxyalkyl Esters and Diesters Based on Hydroxyphenylacetic Acids
title_full_unstemmed Synthesis of Novel Bioactive Lipophilic Hydroxyalkyl Esters and Diesters Based on Hydroxyphenylacetic Acids
title_short Synthesis of Novel Bioactive Lipophilic Hydroxyalkyl Esters and Diesters Based on Hydroxyphenylacetic Acids
title_sort synthesis of novel bioactive lipophilic hydroxyalkyl esters and diesters based on hydroxyphenylacetic acids
topic hydroxyphenylacetic acids
hydroxyalkyl esters
butyl diarylacetates
lipophilicity
antioxidant activity
DPPH assay
url https://www.mdpi.com/1420-3049/30/15/3087
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