Farnesol is a natural 15-carbon organic compound which is an acyclic sesquiterpene alcohol. Under standard conditions, it is a colorless liquid. It is hydrophobic, and thus insoluble in water, but miscible with oils.
Farnesol is produced from 5-carbon isoprene compounds in both plants and animals. Phosphate-activated derivatives of farnesol are the building blocks of possibly all acyclic sesquiterpenoids. These compounds are doubled to form 30-carbon squalene, which is the precursor for steroids in plants, animals, and fungi. Farnesol and its derivatives are important starting compounds for natural and artificial organic synthesis.
Uses
Farnesol is present in many essential oils such as citronella, neroli, cyclamen, lemon grass, tuberose, rose, musk, balsam, and tolu. It is used in perfumery to emphasize the odors of sweet, floral perfumes. It enhances perfume scent by acting as a co-solvent that regulates the volatility of the odorants. It is especially used in lilac perfumes.
Farnesol is a natural pesticide for mites and is a pheromone for several other insects.
In a 1994 report released by five top cigarette companies, farnesol was listed as one of 599 additives to cigarettes. It is a flavoring ingredient.
Farnesol is produced from isoprene compounds in both plants and animals. When geranyl pyrophosphate reacts with isopentenyl pyrophosphate, the result is the 15-carbon farnesyl pyrophosphate (FPP), also known as farnesyl diphosphate (FDP), which is an intermediate in the biosynthesis of sesquiterpenes such as farnesene. Oxidation can then provide sesquiterpenoids such as farnesol.
Farnesyl pyrophosphate (FPP), also known as farnesyl diphosphate (FDP), is an intermediate in the biosynthesis of terpenes and terpenoids such as sterols and carotenoids. It is also used in the synthesis of CoQ (part of the electron transport chain), as well as dehydrodolichol diphosphate (a precursor of dolichol, which transports proteins to the ER lumen for N-glycosylation). Farnesyl pyrophosphate is a selective agonist of TRPV3.
The term farnesene refers to a set of six closely related chemical compounds which all are sesquiterpenes. α-Farnesene and β-farnesene are isomers, differing by the location of one double bond. α-Farnesene is 3,7,11-trimethyl-1,3,6,10-dodecatetraene and β-farnesene is 7,11-dimethyl-3-methylene-1,6,10-dodecatriene. The alpha form can exist as four stereoisomers that differ about the geometry of two of its three internal double bonds (the stereoisomers of the third internal double bond are identical). The beta isomer exists as two stereoisomers about the geometry of its central double bond.
Two of the α-farnesene stereoisomers are reported to occur in nature. (E,E)-α-Farnesene is the most common isomer. It is found in the coating of apples, and other fruits, and it is responsible for the characteristic green apple odour. Its oxidation by air forms compounds that are damaging to the fruit. The oxidation products injure cell membranes which eventually causes cell death in the outermost cell layers of the fruit, resulting in a storage disorder known as scald. Injury to fruit surfaces by naturally occurring gases produced by the fruit? (Z,E)-α-Farnesene has been isolated from the oil of perilla. Both isomers are also insect semiochemicals; they act as alarm pheromones in termites or food attractants for the apple tree pest, the codling moth. α-Farnesene is also the chief compound contributing to the scent of gardenia, making up ~65% of the headspace constituents.
Šobotník, J.; Hanus, R.; Kalinová, B.; Piskorski, R.; Cvačka, J.; Bourguignon, T.; Roisin, Y. (April 2008), “(E,E)-α-Farnesene, an Alarm Pheromone of the Termite Prorhinotermes canalifrons“, Journal of Chemical Ecology, 34 (4): 478–486, CiteSeerX10.1.1.673.1337, doi:10.1007/s10886-008-9450-2, PMID18386097, S2CID8755176
Hern, A.; Dorn, S. (July 1999), “Sexual dimorphism in the olfactory orientation of adult Cydia pomonella in response to alpha-farnesene”, Entomologia Experimentalis et Applicata, 92 (1): 63–72, doi:10.1046/j.1570-7458.1999.00525.x, S2CID85009862
Wang, Shau-Chun; Tseng, Ting-Yu; Huanga, Chih-Min; Tsaic, Tung-Hu (5 December 2004), “Gardenia herbal active constituents: applicable separation procedures”, Journal of Chromatography B, 812 (1–2): 193–202, doi:10.1016/s1570-0232(04)00680-4, PMID15556498
β-Farnesene has one naturally occurring isomer. The E isomer is a constituent of various essential oils. It is also released by aphids as an alarm pheremone upon death to warn away other aphids. Several plants, including potato species, have been shown to synthesize this pheromone as a natural insect repellent.
Avé, D. A.; Gregory, P.; Tingey, W. M. (July 1987), “Aphid repellent sesquiterpenes in glandular trichomes of Solanum berthaultii and S. tuberosum“, Entomologia Experimentalis et Applicata, 44 (2): 131–138, doi:10.1111/j.1570-7458.1987.tb01057.x, S2CID85582590
In industry, farnesol could be synthesized from linalool. Linalool refers to two enantiomers of a naturally occurring terpene alcohol found in many flowers and spice plants. Linalool has multiple commercial applications, the majority of which are based on its pleasant scent.
History of the name
Farnesol is found in a flower extract with a long history of use in perfumery. The pure substance farnesol was named (c. 1900–1905) after the Farnese acacia tree (Vachellia farnesiana), since the flowers from the tree were the commercial source of the floral essence in which the chemical was identified. Vachellia farnesiana, also known as Acacia farnesiana, and previously Mimosa farnesiana, commonly known as sweet acacia, huisache, or needle bush, is a species of shrub or small tree in the legume family, Fabaceae. Its flowers are used in the perfume industry. The flowers are processed through distillation to produce a perfume called cassie, which has been described as “delicious”. It is widely used in the perfume industry in Europe. Scented ointments from cassie are made in India. In Brazil, some people use the seeds of V. farnesiana to kill rabiddogs. V. farnesiana has been used in Colombia to treat malaria, and in one in vitro study, an ethanol extract from the leaves showed some activity against the malarial pathogenPlasmodium falciparum with an IC50 value of 1 to 2 microgram/millilitre (as did almost everything tested), though it showed no activity in animal models or a ferriprotoporphyrin biomineralization inhibition test. In the Philippines the leaves are traditionally rubbed on the skin to treat skin diseases in livestock. In Malaysia, an infusion of the plant’s flowers and leaves is mixed with turmeric for post-partum treatment. This particular acacia species, in turn, is named after Cardinal Odoardo Farnese (1573–1626) of the notable Italian Farnese family which (from 1550 though the 17th century) maintained some of the first private European botanical gardens in the Farnese Gardens in Rome. The addition of the -ol ending results from it being chemically an alcohol. The plant itself was brought to the Farnese gardens from the Caribbean and Central America, where it originates.
USDA, NRCS (n.d.). “Vachellia farnesiana“. The PLANTS Database (plants.usda.gov). Greensboro, North Carolina: National Plant Data Team. Retrieved 25 March 2016.
Farnesol is used as a deodorant in cosmetic products. Farnesol is subject to restrictions on its use in perfumery, because some people may become sensitised to it.
Kromidas, L; Perrier, E; Flanagan, J; Rivero, R; Bonnet, I (2006). “Release of antimicrobial actives from microcapsules by the action of axillary bacteria”. International Journal of Cosmetic Science. 28 (2): 103–108. doi:10.1111/j.1467-2494.2006.00283.x. PMID18492144. S2CID46366332.
Farnesol is used by the fungus Candida albicans as a quorum sensing molecule that inhibits filamentation. Filamentation is the anomalous growth of certain bacteria, such as Escherichia coli, in which cells continue to elongate but do not divide. The cells that result from elongation without division have multiple chromosomal copies.
Quorum sensing or quorum signalling (QS) is the ability to detect and respond to cell population density by gene regulation. As one example, QS enables bacteria to restrict the expression of specific genes to the high cell densities at which the resulting phenotypes will be most beneficial. Many species of bacteria use quorum sensing to coordinate gene expression according to the density of their local population. In a similar fashion, some social insects use quorum sensing to determine where to nest. Quorum sensing in pathogenic bacteria activates host immune signaling and prolongs host survival, by limiting the bacterial intake of nutrients, such as tryptophan, which further is converted to serotonin. As such, quorum sensing allows a commensal interaction between host and pathogenic bacteria. Quorum sensing may also be useful for cancer cell communications.In addition to its function in biological systems, quorum sensing has several useful applications for computing and robotics. In general, quorum sensing can function as a decision-making process in any decentralized system in which the components have: (a) a means of assessing the number of other components they interact with and (b) a standard response once a threshold number of components is detected.
Ali I, Alfarouk KO, Reshkin SJ, Ibrahim ME (16 January 2018). “Doxycycline as Potential Anti-cancer Agent”. Anti-Cancer Agents in Medicinal Chemistry. 17 (12): 1617–1623. doi:10.2174/1871520617666170213111951. PMID28270076.
Research
Farnesol is studied as a potential treatment for Parkinson’s disease. Farnesol blocks the detrimental effects of PARIS (Zinc finger protein 746 also known as Parkin-interacting substrate (PARIS) is a zinc fingerprotein that, in humans, is encoded by the ZNF746gene and is involved (accumulation?) in the neurodegeneration of Parkinson’s disease.) build-up in cells grown in the lab and in mice models.
Kromidas, L; Perrier, E; Flanagan, J; Rivero, R; Bonnet, I (2006). “Release of antimicrobial actives from microcapsules by the action of axillary bacteria”. International Journal of Cosmetic Science. 28 (2): 103–108. doi:10.1111/j.1467-2494.2006.00283.x. PMID18492144. S2CID46366332.
