*2.4.1. Chemical synthesis of phenolic lipids*

conjugated with other compounds, such as flavonoids, alcohols, hydroxyl fatty acids, sterols and glucosides. Phenolic compounds found in foods may be categorized accordingly to three groups, simple phenols and phenolic acids, hydroxycinnamic acid derivatives and flavonoids. The simple phenols include the monophenols, such as p-cresol found in berry fruits (e.g., raspberry, blackberry) and diphenols, such as hydroquinone found commonly in

Phenolic compounds play a major role in the protection against oxidation processes. The antioxidant properties of phenolic compounds can act as free radical scavengers, hydrogen dona-

Phenolic compounds are natural antioxidants that are present in food or in the body, to delay or stop the oxidation of that substance. The main advantages of these natural antioxidant are (1) they are readily acceptable by the consumers; (2) they are considered to be safe; (3) no safety tests are required by legislation; and (4) this natural antioxidant is identical to the food which people have taken over a hundred years or have been mixing with food. Phenolic compounds are associated with nutritional and organoleptic qualities of foods from plant origin [24, 26]. Phenolic compounds at low concentration protect foods from autoxidation, but at high concentration, they can cause undesirable discoloration as a result of their interaction

Among naturally found phenolic compounds, phenolic acids are of high interest due to their potential biological properties [27, 28]. Many phenolic acids are known to be potent antioxidants through their radical scavenging activity, and due to their chemical structure, the reactivity of phenolic acids increases as the number of hydroxyl and methoxyl groups increases [29]. The consumption of fruits, vegetables, and soft drinks such as tea and coffee, which contain phenolic compounds, has been linked to lower risk of some diseases, such as cancer and CVD [30, 31]. However, the use of phenolic acids as natural antioxidants in foods and nutraceutical supplements has the limitation of low solubility in oil-based media. Nevertheless, lipase-catalyzed reactions of lipids with phenolic acids could produce structured lipids with phenolic moieties, which would have health benefits and improved solubility characteristics

Phenolic lipids (PL) are types of fats and oils modified to improved nutritional or physical properties by incorporating phenol compound on the glycerol backbone. Phenolic lipids play an important role as antioxidant and biological active compounds, but their contents in the nature are minor, and the procedures for separation and purification are not easy, very expensive and take a long time, which makes their applications in the food or cosmetic industry very inconvenient. Consequently, the synthesis of PL has attracted more attention in recent years because it is a good way to improve the hydrophobic nature of phenolic compounds,

tors, metal chelators and singlet oxygen quenchers [25, 26].

94 Phenolic Compounds - Natural Sources, Importance and Applications

*2.3.1. Nutritional and antioxidant properties*

with the carbohydrate or protein components.

**2.4. Synthesis of phenolic lipid (PL) compounds**

which could be achieved by chemical or enzymatic synthesis.

vanilla [5, 24].

[32–35].

Chemical synthesis is a traditional method that is used for PL preparation. Synthesis of PL through chemical synthesis could be done by using Friedel-Crafts acylation reaction or Fisher acid catalysis esterification. These processes are generally carried out at relatively high temperatures and pressures under anhydrous conditions, using rather unspecific alkali metal or alkali catalysts. Some related works have been provided in this topic, one of them is the work of Qianchun et al. [36] about the chemical synthesis of phytosterol esters of polyunsaturated fatty acids (PUFAs), which could be used in different formulations of functional foods. Direct esterification of phytosterols with PUFA was catalyzed by sodium bisulfate to produce sterol esters of PUFA without organic solvent. The modeling of sodium bisulfate with superfluous fatty acids as solvents to synthesize phytosterol esters of PUFA was successfully performed with degree of esterification up to 96% and less oxidative products in the reaction process [36].

The chemical esterification of flavonoids with some fatty acids was provided by [37] and its product exhibited lipophilic, antiradical and antioxidant properties. In works reported by Zhong and Shahidi [38, 39] on epigallocatechin gallate (EGCG), the predominant catechin in tea was structurally modified by esterification with fatty acids, including stearic acid (SA), docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The esterification of EGCG with these fatty acids using acylating agents, namely, the acyl chlorides, resulted in yields of 65.9, 42.7 and 30.7 for SA, EPA and DHA, respectively [39]. This esterification leads to produce various compounds that have anti-inflammatory effect and also shows higher inhibition effect against hydroxyl and peroxyl radical-induced DNA scission [38]. Phenolic lipid (PL) chemical synthesis meets some partial needs; this pattern possesses a low degree of regioselectivity and is generally accompanied by drastic reaction conditions, many intermediary stages and purification steps to remove by-products and catalyst residues. The main drawbacks to chemical transesterification are (1) non-selectivity leading to random distribution of FAs, (2) isomerization of sensitive PUFAs by the alkali catalyst, (3) production of fatty acid soaps and unwanted by-products and (4) requiring substantial post-treatment and downstream processes, especially when food applications are concerned.

### *2.4.2. Enzymatic synthesis of phenolic lipids (PLs)*

The application of enzymes is widely in different fields such as pharmaceutical, cosmetic and food industry. Enzymatic synthesis of PL from fats and oils is receiving a lot of attention as a method for their modification because of the advantages of milder reaction conditions, minimization of side reactions and by-product formation, a selective specificity, a wider variety of pure synthetic substrates, fewer purification steps and a more environmentally friendly process [40]. Even if enzymes may be more expensive than chemical reagents, the enzymecatalyzed acylation is a well-mastered technique for synthesis of selectively modification of PL at present. A high degree of conversion to the desired products could be achieved under the optimal reaction conditions. The enzymatic processes can be used in the production of fats and oils containing beneficial fatty acids and phenolic compounds. Some reviews have given a comprehensive understanding and shown a whole outline on the enzymatic synthesis of PL [41–46].

In particular, enzymes appear to be very effective for the synthesis of molecules involving the grafting of a lipophilic moiety or a hydrophilic one. This review will be described and discussed in some of the recent works in the field of enzyme-assisted acylation of fatty acids with phenolic compounds in order to modify the hydrophilic/lipophilic properties of the initial molecules to obtain new products with multifunctional properties combining, for example, antimicrobial, antioxidant and emulsifying properties. The enzymatic synthesis of phenolic lipids has been reported previously in Refs. [10, 45, 47–49]. A lot of enzymes can be used in the synthesis of PL and selectivity is the most important characteristics of enzymes used in phenolic lipid synthesis. Lipase is the most enzymes used in this type of process because of high selectivity, lower overall reaction time and fewer side reactions when compared with chemical methods [50]. An example of a synthesis reaction catalyzed by the lipase is shown in **Figure 4**. This overwhelming interest is based largely on consumers' desire to maintain overall well-being with minimal effort and an industries' ability to respond to this need. Furthermore, with the consumption of manufactured foods continually on the rise, there is a distinct advantage to providing more healthful choices for consumers. The concept of a natural phenolic lipid composed of a longchain aliphatic and phenolic moiety readily fits this mold, particularly since the inclusion of unsaturated lipids into these compounds could result in additional nutritional benefits. Lipases constitute the most important group of biocatalysts for biotechnological applications.

**Figure 4.** Enzymatic synthesis reaction capsiates (fatty vanillyl alcohol acid ester) catalyzed by lipase Novozym 435® [51].

### **2.5. Lipases**

### *2.5.1. Definition, sources, and applications*

Lipase enzymes are defined as glycerol ester hydrolyses that can hydrolyze tri-, di-, and monoacylglycerols [52, 53]. Lipases are soluble in water as a result of their protein nature, but it could act on lipids, which are water insoluble, at the interface between oil and water [53, 54] and catalyze esterification and transesterification in addition to the hydrolytic activity on TAG [55–57]. Lipases are originated from a wide variety of sources including animals, plants and microorganisms. Animal lipases include pregastric esterase, pancreatic lipase, and lingual lipases [53]. Plants such as wheat germ and castor beans also contain lipases [58, 59]. Finally, microbial sources including yeast (*Candida* and *Geotrichum*), molds (*Rhizopus*, *Aspergillus*), and bacteria (*Bacillus*, *Pseudomonas*) [60]. Lipases are widely used because of their ready availability, low cost of production, utility in food, biotechnology, and pharmacology [61]. Novel biotechnological applications have been successfully established using lipases for the synthesis phenolic lipids, the production of pharmaceuticals, agrochemicals, and flavor compounds [52, 62, 63]. Moreover, the use of lipases in the food industry is increasing due to the need for the production of esters, biodegradable polyesters, and specific FAs [64].
