Synthesis and antioxidant properties of pulvinic acids analogues

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 22; pp. 7931 - 7939
• Main Authors: Nadal, Brice, Thetiot-Laurent, Sophie A.-L., Pin, Serge, Renault, Jean-Philippe, Cressier, Damien, Rima, Ghassoub, Le Roux, Antoine, Meunier, Stéphane, Wagner, Alain, Lion, Claude, Le Gall, Thierry
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-11-2010; Elsevier
• Subjects: Acids; Antioxidant; Benzothiazoles - chemistry; beta Carotene - chemistry; beta Carotene - metabolism; Biological and medical sciences; Biphenyl Compounds - chemistry; Carboxylic Acids - chemical synthesis; Carboxylic Acids - chemistry; Carboxylic Acids - pharmacology; Dieckmann condensation; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; Free radicals; General and cellular metabolism. Vitamins; Lactones - chemical synthesis; Lactones - chemistry; Lactones - pharmacology; Medical sciences; Pharmacology. Drug treatments; Picrates - chemistry; Pulvinic acids; Sulfonic Acids - chemistry; Tartrates - chemistry; Thymidine - chemistry; Dieckmann condensation; Free radicals; Antioxidant; Pulvinic acids; Five membered ring; DPPH; Hydroxyester; Benzene derivatives; Lactone; Oxygen heterocycle; In vitro; Radical scavenger; Structure activity relation; Chemical synthesis
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.09.037

The synthesis of 28 pulvinic acids analogues from dimethyl
l-tartrate and the evaluation of their antioxidant properties, using antioxidant capacity assays and free radical scavenging assays, are described.
The synthesis of three types of pulvinic acid analogues, using a diversity-oriented strategy starting from a single compound, dimethyl
l-tartrate, is described. Lacey–Dieckmann condensation, alcohol dehydration and Suzuki–Miyaura cross-couplings were employed in the course of the analogues syntheses. The evaluation of the antioxidant properties of the 28 synthesized analogues was carried out using antioxidant capacity assays (protection of thymidine and β-carotene) and free radical scavenging assays (DPPH radical and ABTS radical cation). This allowed to assess the relative influence of the groups bonded to the tetronic ring and to the exocyclic double bond on the activity, as well as the importance of this exocyclic double bond. It was shown that the presence of an electron-donating group on the 3-position of the tetronic ring had a beneficial effect. It was shown in several assays that the presence of the exocyclic bond was not crucial to the activity.