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Eugenol: Source, processing, and its derivative compounds

Eugenol (C10H12O2, Figure 1, a) is a phenylpropanoid compound with the IUPAC name of 4-allyl-2-methoxyphenol and biosynthesized from the phenylalanine amino acid. Eugenol has an aromatic odor of clove and unique spicy taste with colorless to pale yellow oily liquid. A large number of scientific evidences reported the bioactivities of eugenol, such as antioxidant (Gulcin, 2011), antibacterial (Jeyakumar and Lawrence, 2021), antifungal (Ju et al., 2020), anticancer (Fangjun and Zhijia, 2018), anti-inflammatory (Megalhaes et al., 2019), and others. Therefore, eugenol is widely used in the pharmaceutical, food, and cosmetic industries as well as a raw material for other chemical products due to its properties. Regarding to its toxicity, a dose of eugenol at 2.5 mg/kg body weight is reported as safe (Ulanowska and Olas, 2021).

Figure 1. Molecular structure of eugenol and its derivatives: (a) eugenol, (b) methyleugenol,

(c) isoeugenol, and (d) vanillin.

In 1929, eugenol was firstly isolated as a volatile compound from Eugenia caryophyllata (synonym of Syzygium aromaticum) and the name is supposedly derived according to this genus (Marchese et al., 2017). It is known that eugenol is the most important compound in the clove essential oil. This oil from clove flower buds contains a large amount of eugenol up to 180 mg per g of fresh material (Raja et al., 2015). The concentration of eugenol from other plant organs of clove is lower compared to the flower buds. Cinnamon, nutmeg, basil or tulsi, betel pepper, clover pepper, turmeric, thyme, oregano, ginger, and bay are another well known natural source of eugenol and their concentration in the essential oils are varied according the parts of these plant source. However, these sources have a low concentration of eugenol, namely less than 36 mg per g, compared to the clove (Giuliani, 2014, Raja et al., 2015, Marchese et al., 2017). Up to date, essential oils of clove from Indonesia remain as one potential source of eugenol in the market.

Essential oils from clove containing eugenol are extracted by using conventional extraction methods, solvent extraction, hydro distillation, and steam distillation (Khalil et al., 2017, Haro-Gonzalez et al., 2021). The use of solvent extraction method both in batch and soxhlet extractions faces major hindrances, such as the presence of solvent residue, other soluble residue undesirable flavor changes, and so on. On the other hand, hydro distillation and steam distillation are the most common methods for the extraction of essential oils from clove. Essential oils with eugenol contents of 50–87% were obtained from clove flower buds with high yields of 12–21% by hydro distillation method (Frohlich et al., 2019). These yields and eugenol contents using hydro distillation are similar to the extraction result by the use of supercritical CO2 which is known as a green and efficient extraction method. Another green techniques, microwave and ultra-sound assisted extractions can be also used for the extraction of eugenol to replace the conventional techniques (Khalil et al., 2017). To increase in the eugenol content, several methods purifying eugenol from the clove essential oil have been reported by employing some techniques, e.g., high performance liquid chromatography (Miller et al., 1979) and high-speed counter-current chromatography (Geng et al., 2007). PT Mitra Ayu Adi Pratama applies fractional distillation as another type of refining method to purify clove essential oil with eugenol content ≥ 99.5% to achieve the USP grade of eugenol.

Some experimental reports show eugenol is used as a target molecule for the structural modification in order to produce other derivatives with better and healthier biological effects, lower side effects, and new spectrum of activities and applications. da Silva et al. (2018) modified the eugenol structure using esterification reactions in the hydroxyl group and addition reactions in double bond of the allyl group to enhance antibacterial and antioxidant activities. Esterification and epoxidation reactions of eugenol could improve insecticidal activity (Fernandes et al., 2020). Some eugenol derivatives produced through the following reactions described below: (1) methylation (methyleugenol); (2) isomerization (isoeugenol); and (3) bioengineering (vanillin).

(1) Methyleugenol (Figure 1, b)

Methyleugenol is a natural compound of numerous essential oils of plant origin. The content of methyleugenol in essential oils varies within and between plant families as well as within plant organs. The following plants contain more than 90% methyleugenol as the main compound in essential oils: Melaleuca (M.) bracteata F.v.M. leaves, Cinnamomum (C.) oliveri Bail. leaves, Dacrydium franklinii, M. leucadendron, Crotonn malambo, C. cordatum, M. ericifolia, M. quinquenervia, Pimenta racemose, Piper divaricatum, and Clusena anisate (Burfield, 2004, Burdock, 2005, Tan and Nishida, 2012). Due to the increasing demand, methyleugenol is chemically produced by methylation of eugenol. This reaction involves an addition of a methyl group on the oxygen atom of the hydroxyl group of eugenol based on Williamson ether synthesis in the presence of methylation agent, such as dimethyl carbonate, methyl halides, dimethyl sulphate, etc., and catalyst, such as KOH, bentonite, etc. (Asnawati et al., 2015, Riyanto et al., 2016).

Methyleugenol is a colorless to pale yellow liquid with a clove-carnation odor and a bitter taste. In nature, methyleugenol has various roles related to the chemical defense of plants, namely antifungal, antibacterial, antinematoda, toxicant against pathogens and insect herbivores as well as insect attractant, and sex pheromone (Tan and Nishida, 2012). Gogoi et al. (2020) reported some potential bioactivities of methyleugenol as antioxidant, anti-inflammatory, antimicrobial, genotoxicity, and herbicidal activities. It is used as flavoring agents of ice cream, candy and so on, and a fragrance ingredient in perfumes, toiletries and detergents (National Toxicology Program, 2010b).

(2) Isoeugenol (Figure 1, c)

Some plants, i.e. calamus, savory, basil, clove, nutmeg etc., are source of isoeugenol. However, isoeugenol in nature is present in a small quantity (Galopin et al., 2006). Isoeugenol can be easily isomerized from eugenol wherein the double bond in alkenyl group of eugenol migrates to a position conjugated with the benzene ring. Isomerization of eugenol is carried out by potassium hydroxide in the presence of alcohol and also by a catalyst of rhodium chloride in aqueous alcohol solution at high temperature (Červený et al., 1987). Other modified catalysts, mesoporous silica of SBA-16 containing titanium chloride (Wróblewska et al., 2021) and hydrotalcite-like lattice (Kishore and Kannan, 2004) have a superior performance of isomerization yield compared to that using the conventional base isomerization.

Isoeugenol has a spicy, carnation-like odor which can be incorporated into numerous household and personal hygiene products (National Toxicology Program, 2010a). In addition, isoeugenol is used as sweetener, natural antioxidant, and storage agent in food and pharmaceutical processes (Zhang et al., 2017). Isoeugenol also exhibited the higher biological activities such as antioxidant and antibacterial activities as well as protective effect against DNA damage, than eugenol (Zhang et al., 2017). Isoeugenol is used as a starting material for the biotechnological production of vanillin (Ma et al., 2022).

(3) Vanillin (Figure 1, d)

Vanillin, the world most popular flavor compound, is obtained as a main ingredient of vanilla extract from the fermented pods of vanilla, Vanilla (V.) planifolia and V. tahitensis (Rao and Ravishankar, 2000). In cured vanilla pods, vanillin is present at a concentration of 1–2% (w/w) and due to its characteristic flavor and fragrance comes mainly from the vanillin, vanillin is called as the key component of vanilla extract (Gallage and Møller, 2018, Zhang and Mueller, 2012). Biotechnology-based vanillin synthesis with the use of eugenol, isoeugenol, and others natural compounds has been extensively investigated by many researchers due to its high demand, limited supply of vanilla pods and increasing the production cost of natural vanillin from the cured vanilla pods (Gallage and Møller, 2015, Ma et al., 2022). Bioengineering of vanillin from eugenol and isoeugenol by microorganisms has been reviewed by Gallage and Møller (2015). A higher vanillin production by Amycolatopsis sp. HR167 and Bacillus pumilus S-1 were obtained using eugenol (> 10 g/L, Overhage et al., 2006) and isoeugenol (32.5 g/L, Zhao et al., 2005) as substrates, respectively.

Vanillin is structurally a benzaldehyde substituted with a hydroxyl and methoxy group at positions of C4 and C3, respectively. It is a white crystalline powder with a pleasant, sweet, and intense aroma, offering a vanilla-like flavor as well as a strong milky fragrance. Therefore, vanillin is widely used as an important ingredients in foods, beverages, cosmetics, and pharmaceuticals with the market demand up to 15,000 ton annually (Ma et al., 2022). Bioactive properties of vanillin have been reported by Sinha et al. (2008) and Arya et al. (2021) and others. Some bioactivities of vanillin are as neuroprotection, anticarcinogenic, antioxidant, antimicrobial, hypolipidemic, antisickling, antimutagenic and so on.

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1. Arya, S.S., Rookes, J.E., Cahill, D.M., Lenka, S.K. (2021). Vanillin: a review on the therapeutic prospects of a popular flavouring molecule. Advances in Traditional Medicine, 21: 1–17.

2. Asnawati, D., Sudarma, I.M., Yuanita, E., Arlina, B.F., Hamdiani, S., and Kamali, S.R. (2015). Methylation of eugenol using methyl carbonate and bentonite as catalyst. Indonesian Journal of Chemistry, 15: 256–262.

3. Burdock, G.A. (2005). Fenaroli’s Handbook of Flavor Ingredients, 5th ed. Boca Raton, FL: CRC Press, pp. 672–673.

4. Burfield, T. (2004). Various references re: methyl eugenol content of essential oils, In: Blue Cypress oil (Callitris intratropica Benth. et Hook f.) etc. Cropwatch Issue 3.

5. Červený, L., Krejčiková, A., Marhoul, A., and R╫žička, V. (1987). Isomerization of eugenol to isoeugenol. Reaction Kinetics and Catalysis Letters, 33: 471–476.

6. da Silva, F.F.M., Monte, F.J.Q., de Lemos, T.L.G., do Nascimento, P.G.G., Costa, A.K.M., and de Paiva, L.M.M. (2018). Eugenol derivatives: synthesis, characterization, and evaluation of antibacterial and antioxidant activities. Chemistry Central Journal, 12: 34.

7. Fernandes, M.J.G., Pereira, R.B., Pereira, D.M., Fortes, A.G., Castanheira, E.M.S., and Goncalves, M.S.T. (2020). New eugenol derivatives with enhanced insecticidal activity. International Journal of Molecular Sciences, 21: 9257.

8. Fangjun, L., and Zhijia, Y. (2018). Tumor suppressive roles of eugenol in human lung cancer cells. Thoracic Cancer, 9: 25–29.

9. Frohlich, P.C., Santos, K.A., Palu, F., Cardozo-Filho, L., da Silva, C., and da Silva, E.A. (2019). Evaluation of the effects of temperature and pressure on the extraction of eugenol from clove (Syzygium aromaticum) leaves using supercritical CO2. The Journal of Supercritical Fluids, 143: 313–320.

10. Gallage, N.J., and Møller, B.L. (2015). Vanillin-bioconversion and bioengineering of the most popular plant flavor and its de novo biosynthesis in the vanilla orchid. Molecular Plant, 8: 40–57.

11. Gallage, N.J., and Møller, B.L. (2018). Vanilla: the most popular flavor. In: Biotechnology of natural products. Springer, pp 3–24.

12. Galopin, C.C., Bologa, C., and de Voe, W.B. (2006). The spectator role of potassium hydroxide in the isomerization of eugenol to isoeugenol. In Flavour Science: Recent Advances and Trends (Bredie, W.L.P. and Petersen, M.A, Eds). Elsevier, p. 229–232.

13. Geng, Y., Liu, J., Lv, R., Yuan, J., Lin, Y., and Wang, X. (2007). An efficient method for extraction, separation and purification of eugenol from Eugenia caryophyllata by supercritical fluid extraction and high-speed counter-current chromatography. Separation and Purification Technology, 57: 237–241.

14. Giuliani, F.R. (2014). The composition, structure, and applications of eugenol. ESSAI, 12: 63–66.

15. Gogoi, R., Loying, R., Sarma, N., Begum, T., Pandey, S.K., and Lal, M. (2020). Comparative analysis of in-vitro biological activities of methyl eugenol rich Cymbopogon khasianus Hack., leaf essential oil with pure methyl eugenol compound. Current Pharmaceutical Biotechnology, 21: 927–938.

16. Gulcin, I. (2011). Antioxidant activity of eugenol: A structure-activity relationship study. Journal of Medicinal Food, 14: 975–985.

17. Haro-Gonzalez, J.N., Castillo-Herrera, G.A., Martinez-Velazquez, M., and Espinosa-Andrews, H. (2021). Clove essential oil (Syzygium aromaticum L. Myrtaceae): Extraction, chemical composition, food applications, and essential bioactivity for human health. Molecules, 26: 6387.

18. Jeyakumar, G.E., and Lawrence, R. (2021). Mechanisms of bactericidal action of eugenol against Escherichia coli. Journal of Herbal Medicine, 26: 100406.

19. Ju, J., Xie, Y., Yu, H., Guo, Y., Cheng, Y., Qian, H., and Yao, W. (2020). Analysis of the synergistic antifungal mechanism of eugenol and citral. LWT – Food Science and Technology, 123: 109128.

20. Khalil, A.A., Rahman, U., Khan, M.R., Sahar, A., Mehmood, T., and Khan, M. (2017). Essential oil eugenol: Source, extraction techniques and nutraceutical perspectives. Royal Society of Chemistry Advances, 7: 32669–32681.

21. Kishore, D., and Kannan, S. (2004). Double bond migration of eugenol to isoeugenol over as0synthesized hydrotalcites and their modified forms. Applied Catalysis A: General, 270: 227–235.

22. Ma, Q., Liu, L., Zhao, S., Huang, Z., Li, C., Jiang, S., Li, Q., and Gu, P. (2022). Biosynthesis of vanillin by different microorganisms: a review. World Journal of Microbiology and Biotechnology, 38: 40.

23. Marchese, A., Barbieri, R., Coppo, E., Orhan, I.E., Daglia, M., Nabavi, S.F., Izadi, M., Abdollahi, M., Nabavi, S.M., and Ajami, M. (2017). Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint. Critical Reviews in Microbiology, 43: 668–689.

24. Megalhaes, C.B., Casquilho, N.V., Machado, M.N., Riva, D.R., Travassos, L.H., Leal-Cardoso, J.H., Fortunato, R.S., Faffe, D.S., and Zin, W.A. (2019). The anti-inflmmatory and anti-oxidative actions of eugenol improve lipopolysaccharide-induced lung injury. Respiratory Physiology and Neurobiology, 259: 30–36.

25. Miller, R.A., Bussell, N.E., Ricketts, C.K., and Jordi, H. (1979). Analysis and purification of eugenol. Journal of Dental Research, 58: 1394–1400.

26. National Toxicology Program (2010a). Toxicology and carcinogenesis studies of isoeugenol (CAS No. 97-54-1) in F344/N rats and B6C3F1 mice (gavage studies). National Toxicology Program Technical Report Series, 551: 1–178.

27. National Toxicology Program (2010b). Toxicology and carcinogenesis studies of methyleugenol (CAS No. 93-15-2) in F344/N rats and B6C3F1 mice. National Toxicology Program Technical Report Series, 491: 1–412.

28. Overhage, J., Steinbuchel, A., and Priefert, H. (2006). Harnessing eugenol as a substrate for production of aromatic compounds with recombinant strains of Amycolatopsis sp HR 167. Journal of Biotechnology, 125: 369–376.

29. Raja, M.R,C., Srinivasan, V., Selvaraj, S., and Mahapatra, S.K. (2015). Versatile and synergistic potential of eugenol: A review. Pharmaceutica Analytica Acta, 6: 1000367.

30. Rao, S.R., and Ravishankar, G.A. (2000). Vanilla flavor: production by conventional and biotechnological routes. Journal of the Science of Food and Agriculture, 80: 289–304.

31. Riyanto, Sastrohamidjojo, H., and Fariyatun, E. (2016). Synthesis of methyl eugenol from crude clove leaf oil using acid and based chemicals reactions. IOSR Journal of Applied Chemistry, 9: 105–112.

32. Sinha, A.K., Sharma, U.K., and Sharma, N. (2008). A comprehensive review on vanilla flavor: Extraction, isolation and quantification of vanillin and others constituents. International Journal of Food Sciences and Nutrition, 59: 299–326.

33. Tan, K.H., and Nishida, R. (2012). Methyl eugenol: Its occurrence, distribution, and role in nature, especially in relation to insect behavior and pollination. Journal of Insect Science, 12: 56.

34. Wróblewska, A., Makuch, E., Retajszyk, M., Sreńscek-Nazzal, J., Koren, Z.C., and Michalkiewicz, B. (2021). Synthesis, characterization and application of the SBA-16 catalyst modified with titanium (IV) chloride in the eugenol isomerization. Microporous and Mesoporous Materials, 311: 110685.

35. Zhang, S., and Mueller, C. (2012). Comparative analysis of volatiles in traditionally cured Bourbon and Ugandan vanilla bean (Vanilla planifolia) extract. Journal of Agricultural and Food Chemistry, 60: 10433–10444.

36. Zhang, L.-L., Zhang, L.-F., Xu, J.-G., and Hu, Q.-P. (2017). Comparison study on antioxidant, DNA damage protective and antibacterial activities of eugenol and isoeugenol against several foodborne pathogens. Food & Nutrition Research, 61: 1353356.

37. Zhao, L.Q., Sun, Z.H., Zheng, P.Z., and Lei, L. (2005). Biotransformation of isoeugenol to vanillin by a novel strain of Bacillus fusiformis. Biotechnology Letters, 27: 1505–1509.

38. Ulanowska, M. and Olas, B. (2021). Biological properties and prospects for the application of eugenol – A review. International Journal of Molecular Science, 11: 3671.

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