Regioselective O-Derivatization of Quercetin via Ester Intermediates. An Improved Synthesis of Rhamnetin and Development of a New Mitochondriotropic Derivative

• Main Authors: Mario Zoratti, Ester Marotta, Spiridione Garbisa, Lucia Biasutto, Federico Rastrelli, Andrea Mattarei, Cristina Paradisi
• Format: Article
• Language: English
• Published: MDPI AG 2010-07-01
• Series: Molecules
• Subjects: regioselective alkylation; mitochondrial targeting; quercetin; rhamnetin; polyphenols
• Online Access: http://www.mdpi.com/1420-3049/15/7/4722/

The regioselective synthesis of several quercetin (3,3’,4’,5,7-pentahydroxy flavone) tetraesters bearing a single free OH on 5-C was achieved in good yield by proper choice of reaction conditions using common esterification procedures. Tetracetylated quercetin with the free OH on 7-C was selectively obtained instead via imidazole-promoted deacylation of the corresponding pentaester. Unambiguous structural characterization of the two isomeric tetraacetyl quercetin derivatives was obtained by combined HSQC and HMBC 2D-NMR analysis. These molecules can be used as starting materials for the regioselective synthesis of other derivatives. High yield syntheses of the natural polyphenol rhamnetin (7-O-methylquercetin) and of the new mitochondriotropic compound 7-(4-triphenylphosphoniumbutyl) quercetin iodide are reported as examples.