New Lipophilic Tyrosyl Esters. Comparative Antioxidant Evaluation with Hydroxytyrosyl Esters

Abstract

New lipophilic esters of tyrosol, a naturally occurring phenol with interesting biological properties, have been synthesized in good yields by a chemoselective procedure, using lipase from Candida antarctica or p-toluenesulfonic acid as catalysts. Their antioxidant activities have been evaluated by the Rancimat test in lipophilic food matrices, as well as by FRAP and ABTS assays in methanolic solutions, and compared with those of previously synthesized hydroxytyrosyl esters. Free tyrosol, hydroxytyrosol, butylhydroxytoluene, and alpha-tocopherol were used as standards. All methods used for the antioxidant activity evaluation emphasized the high influence of the ortho-diphenolic structure on the antioxidant capacity, tyrosol and its derivatives being less active than hydroxytyrosol and its analogues and even less than BHT and alpha-tocopherol. In addition, the Rancimat test revealed a lower activity for ester derivatives than for their respective reference compounds (HTy or Ty), in agreement with the polar paradox. On the other hand, FRAP and ABTS methods reported an opposite behavior between the synthetic esters and their respective references. Thus, hydroxytyrosyl esters were more active than HTy, whereas tyrosyl esters were less active than Ty. The length and nature of the acyl side chain did not seem to play an important role in the antioxidant activity of either the hydroxytyrosyl or tyrosyl ester series, since no significant differences were observed among them.

Biological Properties of Hydroxytyrosol and Its Derivatives

“…These results are in agreement with those obtained in the case of hydroxytyrosyl esters, covered in the previous section (Mateos et al, 2008). The antioxidant activity has been checked by the DPPH, FRAP and ABTS assays in a hydrophilic medium .…”

“…Synthesis of hydroxytyrosyl acetate via benzylation of phenolic hydroxyls A two-step procedure involving the reaction of methyl orthoformate-protected hydroxytyrosol with acetyl chloride, and hydrolytic deprotection in phosphate buffer under very mild conditions (pH=7.2) to get hydroxytyrosyl acetate (87% overall yield) (Scheme 3) was also described as a successful procedure for the preparation of HT-derived esters (Gambacorta et al, 2007 In order to overcome the problems associated to the protection and deprotection steps of the phenolic hydroxyl groups, different methods for the preparation of hydroxytyrosyl esters by reaction of hydroxytyrosol with various acylating agents have been described, such as esterification with free acids (Appendino et al, 2002), transesterification with methyl or ethyl esters (Alcudia et al, 2004;Trujillo et al, 2006), acyl chlorides (Torregiani et al, 2005) and the use of enzymatic methodologies (Grasso et al, 2007;Mateos et al, 2008;Torres de Pinedo et al, 2005;Buisman, 1998).…”

“…This method involves heating a solution solution of hydroxytyrosol in the corresponding ethyl or methyl ester, containing a catalytic amount of p-toluenesulfonic acid (Scheme 4). This protocol has been optimized for HT acetate (86%), and also for longer aliphatic chains like hydroxytyrosyl butyrate, laureate, palmitate, stearate, oleate and linoleate, obtained in acceptable to good yields (62-76%) (Mateos et al, 2008).…”

“…The use of enzymes, like lipases, as catalysts in non-aqueous solvents to prepare lipophilic derivatives directly from HT has been widely described in the last few years (Grasso et al, 2007;Torres de Pinedo et al, 2005;Mateos et al, 2008;Buisman et al, 1998). This procedure avoids the use of toxic reagents and allows mild reaction conditions.…”

“…The antioxidant activity of hydroxytyrosyl esters has been measured with different methods, including DPPH (1,1-diphenyl-2-picrylhydrazyl radical), ABTS (2,2'-azino-bis(3-etilbenzotiazolin-6-sulfonic acid), FRAP (ferric reducing antioxidant power) and Rancimat (Mateos et al, 2008;Gordon et al, 2001;Bouallagui et al, 2011b). The Rancimat test is a method commonly used to evaluate the antioxidant power in lipophilic food matrices, such as oils and fats, while the ABTS and FRAP assays are used for the evaluation of antioxidant activity in hydrophilic medium; the ABTS assay evaluating the radical-scavenging capacity, and the FRAP method determining the reducing activity.…”