Crude peroxidase from onion solid waste as a tool for organic synthesis. Part II: oxidative dimerization–cyclization of methyl p-coumarate, methyl caffeate and methyl ferulate Sonia Moussouni a,  , Maria-Liliana Saru a,  , Efstathia Ioannou b , Mohamed Mansour a , Anastasia Detsi c , Vassilios Roussis b , Panagiotis Kefalas a,⇑ a Department of Food Quality and Chemistry of Natural Products, Mediterranean Agronomic Institute of Chania/Centre International de Hautes Etudes Agronomiques Méditerranéennes, 73100 Chania, Crete, Greece b Department of Pharmacognosy & Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece c Laboratory of Organic Chemistry, Department of Chemical Sciences, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780 Athens, Greece article info Article history: Received 23 September 2010 Revised 15 December 2010 Accepted 4 January 2011 Available online 12 January 2011 Keywords: Onion peroxidase p-Coumaric acid Caffeic acid Ferulic acid Dihydrobenzofuran lignans Antioxidant activity abstract The ability of a crude onion peroxidase preparation to act as a biocatalyst for the oxidative dimerization– cyclization of methyl p-coumarate, methyl caffeate and methyl ferulate is presented. The products of the reaction have been fully characterized and were found to possess potent antioxidant activity in a ferric reducing antioxidant power (FRAP) assay. Ó 2011 Elsevier Ltd. All rights reserved. Oxidative dimerization of phenolic compounds occurs in Nature and leads to the formation of dihydrodimeric products that play a significant role in the cross-linking of plant cell wall components, which in turn influences various important cell wall properties. This biotransformation is catalyzed by enzymes, such as peroxi- dases and polyphenol oxidases including laccases, or, in some cases, occurs via photochemical oxidation. 1–5 Moreover, oxidative cross-linking is very important for the properties and technological applications of biopolymers in which phenolics (feruroyl and cou- maroyl residues) are covalently attached. 6,7 p-Coumaric acid (1), caffeic acid (2), and ferulic acid (3) (Scheme 1) are components of plant cell walls, and are subjected to oxidative dimerization to produce structurally diverse lignan- type natural products. Characteristic examples of common pheno- lic acid dihydrodimers isolated from plants are the ferulic acid di- mers 8-O-4-diFA (compound I), 8,8-diFA (compound II), 5,5-diFA (compound III), and the dihydrobenzofuran lignans (compounds of type IV)(Fig. 1). 8–10 The latter display a wide range of biological activity including antitumor, 11 antiparasitic, 12 and antioxidant, 5 and as a result, have attracted considerable attention as potential synthetic targets with an important bioactivity. The dimerization of phenolic acids to give lignans has been re- ported to occur efficiently mainly using the biomimetic peroxi- dase-H 2 O 2 system, exploiting in most cases horseradish peroxidase, 4,13–16 but also potato peroxidase, 9 Momordica charantia peroxidase, 5 and a peroxidase from the leaves of Bupleurum salicifo- lium. 1 The dihydrobenzofuran dimer of p-coumaric acid has also been produced as a metabolic product of Curvularia lunata, as a re- sult of the presence of peroxidase and laccase in the culture filtrates of this microorganism. 17 In addition, chemical single-electron oxi- dizing systems, such as Ag 2 O or K 3 Fe(CN) 6 , are effective coupling agents for the dimerization of phenolic acids or their esters. 11,12,18 The exploitation of food residuals as sources of crude enzymes can contribute not only to the reduction of the polluting load of food industry wastes, but also to the development of high added value products. As a continuation of our research on the potential biocatalytic activity of crude peroxidase (POD) from onion solid waste, 19 we herein describe the reactions of methyl p-coumarate (4), methyl caffeate (5), and methyl ferulate (6) using this enzymic preparation as a catalyst. The antioxidant activity of the reaction 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.01.004 ⇑ Corresponding author. Tel./fax: +30 2821035056. E-mail address: panos@maich.gr (P. Kefalas).   These two authors contributed equally to this research. Tetrahedron Letters 52 (2011) 1165–1168 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet