Chemo‐enzymatic synthesis and evaluation of novel structured phenolic lipids as potential lipophilic antioxidants

Abstract

Chemo-enzymatic synthesis of structured triacylglycerol bearing ferulic acid as a phenolic acid at sn-1/3 position is described in the present work. Four compounds of varying chain lengths, namely 3-(4-hydroxy-3-methoxy-phenyl)-acrylic acid-2,3-bis-hexanoyloxy-propyl ester, 3-(4-hydroxy-3-methoxy-phenyl)-acrylic acid-2,3-bis-octanoyloxy-propyl ester, 3-(4-hydroxy-3-methoxy-phenyl)-acrylic acid-2,3-bis-dodecanoyloxy-propyl ester, and 3-(4-hydroxy-3-methoxy-phenyl)-acrylic acid-2,3-bis-9-octadecenoyloxy-propyl ester were synthesized, and their structures were confirmed by IR, NMR, and MS. Antioxidant activity of the structured phenolic lipids were evaluated using three different in vitro antioxidant assays such as 2, 2-diphenyl-1-picrylhydrazyl free radical (DPPH ) scavenging, antioxidant potency in lipid matrix using rancimat, and by the rate of inhibition of autoxidation of linoleic acid in micelles. Ferulic acid and dodecylgallate were used as reference antioxidant compounds. DPPH assay did not show any improvement in the antioxidant activity of ferulic acid with lipophilic modification. However, the antioxidant potency of the structured phenolic lipids measured by rancimat method as well as by the rate of inhibition of autoxidation of linoleic acid in micelle showed improvement in antioxidant activity compared to ferulic acid. This is probably due to better solubility of the synthesized phenolic lipids in a hydrophobic medium and appropriate anchorage in Tween 20 micelle. The observed activities of the structured phenolic lipids are comparable to dodecyl gallate in rancimat assay, but superior to dodecyl gallate in Tween 20 micellar system.

Regioselective synthesis of diacylglycerol rosmarinates and evaluation of their antioxidant activity in fibroblasts

“…As depicted on Fig. 2, another addition of DIAD and PPh 3 after 5 h allowed a restart in the esterification process that reached around 91% conversion of rosmarinic acid after 23 h. For comparison, Reddy et al [23] obtained a conversion rate of 58% in 48 h with ferulic acid. Thus, a sequential and dosed addition of PPh 3 and DIAD allowed to significantly improve esterification of phenolic acid using Mitsunobu reaction.…”

“…To date, a multitude of lipophilized antioxidants have been synthesized. Phenolic acids, flavonoids, and tocopherols have been lipophilized with various alkyl chain lengths , phospholipids , and diacylglycerol to obtain multifunctional compounds called “phenolipids.” Ascorbic acid has also been hydrophobized by various saturated or unsaturated acyl chains . In most of cases, the lipophilization proved to be a promising strategy to enhance their natural antioxidant property in biological system or formulated lipid dispersion.…”

“…To date, a multitude of lipophilized antioxidants have been synthesized. Phenolic acids, flavonoids, and tocopherols have been lipophilized with various alkyl chain lengths [16][17][18][19][20], phospholipids [21], and diacylglycerol [22][23][24][25] to obtain multifunctional compounds called "phenolipids." Ascorbic acid has also been hydrophobized by various saturated [26] or unsaturated acyl chains [27].…”

The nonlinear effect of alkyl chain length in the membrane interactions of phenolipids: Evidence by X‐ray diffraction analysis

“…In that context, one strategy to design surface‐active antioxidants consists in their association via covalent bond with a lipophilic moiety to design a new class of molecule called “phenolipids.” Typically, this approach named “lipophilization” corresponds to a strategy where the hydrophilic/lipophilic balance of a bioactive hydrophilic molecule is adjusted by a covalent grafting of a lipophilic domain, without affecting the functional groups responsible of its chemical reactivity. To date, a multitude of antioxidants have been lipophilized with various lipophilic moieties such as alkyl chains , phospholipids , and diacylglycerol to obtain multifunctional compounds.…”

Synthesis and Characterization of a Novel Phenolic Lipid for Use as Potential Lipophilic Antioxidant and as a Prodrug of Butyric Acid

“…To date, there are very few reports on the lipophilization, characterization and evaluation of phenolic compounds with butyric acid and there is an increasing interest observed for the synthesis of this type of molecules 19,20 . As a part of our ongoing research to prepare novel lipophilic antioxidants from phenolic compounds 21,22 , we wish to report the synthesis and characterization of a novel lipophilic phenolic compound derived from ferulic acid Fig. 1 .…”