562-74-3 Usage
Uses
Used in Antimicrobial Applications:
Terpinen-4-ol is used as a potent bactericidal agent for its antifungal properties. It is particularly effective against Staphylococcus aureus and C. albicans, and when combined with conventional drugs, it may help treat resistant yeast and bacterial infections.
Used in Anticancer Applications:
Terpinen-4-ol is used as an anticancer agent for inducing antitumor effects by selectively causing necrotic cell death and cell-cycle arrest in melanoma cell lines, or by triggering caspase-dependent apoptosis in human melanoma cells, particularly in drug (Adriamycin) resistant cells. It also elicits a dose-dependent cytotoxic response on human non-small cell lung cancer cells, presumably through the involvement of the mitochondrial apoptotic pathway.
Used in Perfumery and Fragrance Industry:
Terpinen-4-ol is used as a key component in artificial geranium and pepper oils and in perfumery for creating herbaceous and lavender notes.
Used in Flavor and Food Industry:
Terpinen-4-ol is used for its taste characteristics at 30 ppm, which are sweet, citrus green with a tropical fruity character. It is found in fresh apple, apricots, orange juice, and peel oils of orange, lemon, grapefruit, tangerines, anise, cinnamon, ginger, and nutmeg.
Used in Pharmaceutical Industry:
Terpinen-4-ol is used as a pharmaceutical candidate due to its antimicrobial, anti-viral, anti-fungal, anti-oxidant, anti-inflammatory, and anti-cancer activities. It is a major plant-derived secondary metabolite widely found in natural products, including fruits, vegetables, and herbs, and is known to be associated with plant defense mechanisms.
Biological activities
Terpinen-4-ol contained in TTO confers its various biological effects. Terpinen-4-ol is the major active component of tea tree oil. Terpinen-4-ol gained attention because of its antibacterial, antifungal, antiviral, and anti-inflammatory properties.
Antibacterial activity
erpinen-4-ol contained in TTO confers its remarkable antibacterial activity. Most bacteria are susceptible to TTO at concentrations of 1.0% or less; MICs in excess of 2% have been reported for organisms such as commensal skin staphylococci and micrococci, Enterococcus faecalis, and Pseudomonas aeruginosa[18]. TTO is for the most part bactericidal in nature, although it may be bacteriostatic at lower concentrations. The activity of TTO against antibiotic-resistant bacteria has attracted considerable interest, with methicillin-resistant Staphylococcus aureus (MRSA) receiving the most attention thus far. Since the potential to use TTO against MRSA was first hypothesized[19], several groups have evaluated the activity of TTO against MRSA, beginning with Carson et al.[20]?who examined 64 MRSA isolates from Australia and the United Kingdom, including 33 mupirocin-resistant isolates. When the effects of terpinen-4-ol on S. aureus were examined, none was found to induce autolysis but was found to cause the leakage of 260-nmlightabsorbing material and to render cells susceptible to sodium chloride[21]. Electron microscopy of terpinen-4-ol-treated S. aureus cells revealed lesions similar to those seen after TTO treatment[22], including mesosome-like structures. In summary, the loss of intracellular material, inability to maintain homeostasis, and inhibition of respiration after treatment with terpinen-4-ol is consistent with a mechanism of action involving the loss of membrane integrity and function.
Antiprotozoal activity
Two publications show that TTO has antiprotozoal activity. TTO caused a 50% reduction in growth (compared to controls) of the protozoa Leishmania major and Trypanosoma brucei at concentrations of 403 mg/ml and 0.5 mg/ml, respectively[23]. In another study, TTO at 300 mg/ml killed all cells of Trichomonas vaginalis. There is also anecdotal in vivo evidence that TTO may be effective in treating Trichomonas vaginalis infections[24]. Further investigation showed that terpinen-4-ol contributed significantly to this activity.
Anti-Mites activity
It has been reported that lid scrub with different concentrations of TTO is effective in reducing Demodex mite counts and ocular surface inflammation associated with blepharitis, conjunctivitis, and keratitis[25, 26]. Terpinen-4-ol is the most active ingredient in TTO in exerting Demodex mite-killing effects.
Anti-inflammatory activity
Numerous recent studies now support the anecdotal evidence attributing anti-inflammatory activity to TTO. In vitro work over the last decade has demonstrated that TTO affects a range of immune responses, both in vitro and in vivo. It can inhibit the lipopolysaccharide-induced production of the inflammatory mediators tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-10 by human peripheral blood monocytes and that of prostaglandin E2. Terpinen-4-ol plays a major role in the anti-inflammatory effect of TTO. Terpinen-4-ol was able to diminish the production of TNF--alpha, IL-1 beta, IL-8, IL-10, and prostaglandin E2 by lipopolysaccharide-activated monocytes. Terpinen-4-ol also suppressed superoxide production by agonist-stimulated monocytes but not neutrophils[27]. TTO failed to suppress the adherence reaction of neutrophils induced by TNF-alpha stimulation or the casein-induced recruitment of neutrophils into the peritoneal cavities of mice. These studies identify specific mechanisms by which TTO may act in vivo to diminish the normal inflammatory response. In vivo, topically applied TTO has been shown to modulate the edema associated with the efferent phase of a contact hypersensitivity response in mice[28] but not the development of edema in the skin of nonsensitized mice or the edematous response to UVB exposure. This activity was attributed primarily to terpinen-4-ol. TTO and terpinen-4-ol applied after histamine injection reduced histamine-induced skin edema, and TTO also significantly reduced swelling induced by intradermal injection of compound 48/80[29]. Work has now shown that terpinen-4-ol modulates the vasodilation and plasma extravasation associated with histamine-induced inflammation in humans.
Anti-cancer
The anticancer effects of terpinen-4-ol are impressive in various types of cancer cells both in vitro and in vivo. Terpinen-4-ol is a major component of essential oil derived from several aromatic plants. It is used as an anti-inflammatory and antioxidant agent[15–17]. The contribution of terpinen-4-ol as an anti-cancer agent and the underlying signaling pathways of different types of cell death are unknown. Herein, it is shown that the mechanism of action of terpinen-4-ol is induction of apoptosis and not necrosis. It is also shown that terpinen-4-ol and various anticancer agents demonstrate a synergistic growth inhibitory effect by decreasing the survival of various cancer cell lines. Such combinations maybe expected to be more effective and less toxic since lower drug concentrations can be used for treating a wide range of cancers. Injection of terpinen-4-ol into the tumor remarkably inhibited tumor growth without any significant adverse effects. In search for more convenient routes of administration, two pharmaceutical formulations were prepared and tested for systemic administration, nano formulation and suspension. Nano formulations increased the surface area and therefore dramatically improved water solubility, bioavailability, effectiveness and efficiency. The suspension form was composed of small drops/molecules of the therapeutically active ingredient (the oil) in a suspension medium. Since the nanodrops were associated with serious toxicity (loss of body weight, mortality), the suspension approach that was devoid of any side effects was chosen for further exploration. The systemic administration of terpinen-4-ol by suspension was associated with a significant reduction in tumor size in the experimental nude mice.
References
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Calcabrini A, Stringaro A, Toccacieli L, Meschini S, Marra M, Colone M, et al. (2004) Terpinen-4-ol, the main component of Melaleuca alternifolia (tea tree) oil inhibits the in vitro growth of human melanoma cells. J Invest Dermatol 122: 349–360.
Arweiler NB, Donos N, Netuschil L, Reich E, Sculean A (2000) Clinical and antibacterial effect of tea tree oil—a pilot study. Clin Oral Investig 4: 70–73.
Gershenzon J, Dudareva N (2007) The function of terpene natural products in the natural world. Nat Chem Biol 3: 408–414. PMID: 17576428
Wagner KH, Elmadfa I (2003) Biological relevance of terpenoids. Overview focusing on mono-, diand tetraterpenes. Ann Nutr Metab 47: 95–106. PMID: 12743459
Gould MN (1997) Cancer chemoprevention and therapy by monoterpenes. Environ Health Perspect 105 Suppl 4: 977–979. PMID: 9255590
Da Fonseca CO, Masini M, Futuro D, Caetano R, Gattass CR, Quirico-Santos T (2006) Anaplastic oligodendroglioma responding favorably to intranasal delivery of perillyl alcohol: a case report and literature review. Surg Neurol 66: 611–615. PMID: 17145324
da Fonseca CO, Schwartsmann G, Fischer J, Nagel J, Futuro D, Quirico-Santos T, et al. (2008) Preliminary results from a phase I/II study of perillyl alcohol intranasal administration in adults with recurrent malignant gliomas. Surg Neurol 70: 259–266; discussion 266–257.
Sobral Marianna Vieira X AL, Lima Tamires Cardoso, and de Sousa Dami?o Pergentino (2014) Antitumor Activity of Monoterpenes Found in Essential Oils. The Scientific World Journal 2014.
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Loughlin R, Gilmore BF, McCarron PA, Tunney MM (2008). Lett Appl Microbiol 46: 428–433. doi: 10.1111/j.1472-765X.2008.02334.x
Mondello F, De Bernardis F, Girolamo A, Cassone A, Salvatore G (2006) BMC Infect Dis 6: 158.
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Mertas A, Garbusinska A, Szliszka E, Jureczko A, Kowalska M, KrolW(2015) Biomed Res Int 2015: 590470. doi: 10.1155/2015/590470
Greay SJ, Ireland DJ, Kissick HT, Levy A, Beilharz MW, Riley TV, et al. (2010) Cancer Chemother Pharmacol 65: 877–888.
Calcabrini A, Stringaro A, Toccacieli L, Meschini S, Marra M, Colone M, et al. (2004) Terpinen-4-ol, The Main Component of Melaleuca Alternifolia (Tea Tree) Oil Inhibits the In Vitro Growth of Human Melanoma Cells. J Investig Dermatol 122: 349–360.
Wu CS, Chen YJ, Chen JJ, Shieh JJ, Huang CH, Lin PS, et al. (2012) Terpinen-4-ol Induces Apoptosis in Human Nonsmall Cell Lung Cancer In Vitro and In Vivo. Evid Based Complement Alternat Med 2012: 818261. doi: 10.1155/2012/818261
Banes-Marshall, L., P. Cawley, and C. A. Phillips. 2001. Br. J. Biomed. Sci. 58:139–145.
Walsh, L. J., and J. Longstaff. 1987. The antimicrobial effects of an essential oil on selected oral pathogens. Periodontology 8:11–15.
Carson, C. F., B. D. Cookson, H. D. Farrelly, and T. V. Riley. 1995. Susceptibility of methicillin-resistant Staphylococcus aureus to the essential oil of Melaleuca alternifolia. J. Antimicrob. Chemother. 35:421–424.
Carson, C. F., B. J. Mee, and T. V. Riley. 2002. Mechanism of action of Melaleuca alternifolia (tea tree) oil on Staphylococcus aureus determined by time-kill, lysis, leakage, and salt tolerance assays and electron microscopy. Antimicrob. Agents Chemother. 48:1914–1920.
Reichling, J., A. Weseler, U. Landvatter, and R. Saller. 2002. Bioactive essential oils used in phytomedicine as antiinfective agents: Australian tea tree oil and manuka oil. Acta Phytotherapeutica 1:26–32.
Mikus, J., M. Harkenthal, D. Steverding, and J. Reichling. 2000. In vitro effect of essential oils and isolated monoand sesquiterpenes on Leishmania major and Trypanosoma brucei. Planta Med. 66:366–368.
Pen?a, E. F. 1962. Melaleuca alternifolia oil—its use for trichomonal vaginitis and other vaginal infections. Obstet. Gynecol. 19:793–795.
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Brand, C., A. Ferrante, R. H. Prager, T. V. Riley, C. F. Carson, J. J. Finlay-Jones, and P. H. Hart. 2001. The water soluble-components of the essential oil of Melaleuca alternifolia (tea tree oil) suppress the production of superoxide by human monocytes, but not neutrophils, activated in vitro. Inflamm. Res. 50:213–219.
Brand, C., M. A. Grimbaldeston, J. R. Gamble, J. Drew, J. J. Finlay-Jones, and P. H. Hart. 2002. Tea tree oil reduces the swelling associated with the efferent phase of a contact hypersensitivity response. Inflamm. Res. 51:236–244.
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Flammability and Explosibility
Notclassified
Biochem/physiol Actions
Taste at 30 ppm
Anticancer Research
Also this molecule exhibits antitumor effects by apoptotic mechanism. Studies weredone in mice bearing A549 tumor xenografts (Quintans et al. 2013; Kiyan et al.2014).
Synthesis
One of several terpinenol isomers, depending on the position of the double bond and that of the hydroxyl group, this terpene,
whose structure has been defined by Wallach, can be isolated by fractional distillation. It exists in nature as the dextro, levo and
racemic isomer; the synthetic product is always optically inactive. The 1-terpineneol or 1-meththyl-4-isopropyl-3-cyclohexen-1-ol has
been prepared by Wallach (Burdock, 1997).
Check Digit Verification of cas no
The CAS Registry Mumber 562-74-3 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,6 and 2 respectively; the second part has 2 digits, 7 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 562-74:
(5*5)+(4*6)+(3*2)+(2*7)+(1*4)=73
73 % 10 = 3
So 562-74-3 is a valid CAS Registry Number.
InChI:InChI=1/C10H18O/c1-8(2)10(11)6-4-9(3)5-7-10/h4,8,11H,5-7H2,1-3H3
562-74-3Relevant articles and documents
Synthesis of Terpineol from Alpha-Pinene Catalyzed by α-Hydroxy Acids
Hu, Yi-Ming,Huang, Xiao-Rui,Meng, Zhong-Lei,Qin, Rong-Xiu,Wen, Ru-Si,Zhou, Yong-Hong
, (2022/02/17)
We report the use of five alpha-hydroxy acids (citric, tartaric, mandelic, lactic and glycolic acids) as catalysts in the synthesis of terpineol from alpha-pinene. The study found that the hydration rate of pinene was slow when only catalyzed by alpha-hydroxyl acids. Ternary composite catalysts, composed of AHAs, phosphoric acid, and acetic acid, had a good catalytic performance. The reaction step was hydrolysis of the intermediate terpinyl acetate, which yielded terpineol. The optimal reaction conditions were as follows: alpha-pinene, acetic acid, water, citric acid, and phosphoric acid, at a mass ratio of 1:2.5:1:(0.1–0.05):0.05, a reaction temperature of 70? C, and a reaction time of 12–15 h. The conversion of alpha-pinene was 96%, the content of alpha-terpineol was 46.9%, and the selectivity of alpha-terpineol was 48.1%. In addition, the catalytic performance of monolayer graphene oxide and its composite catalyst with citric acid was studied, with acetic acid used as an additive.
PROCESS FOR PREPARING A MIXTURE OF TERPENE ALCOHOLS
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Page/Page column 13, (2017/09/15)
The present invention relates to a process for preparing a mixture of terpene alcohols comprising limonene-4-ol and terpinene-4-ol from terpinolene epoxide via an isomerization and/or hydrogenation reaction in the presence of a copper catalyst.
PROCESS FOR PREPARING TERPINENE-4-OL
-
Page/Page column 9; 10; 11, (2017/09/09)
The present invention relates to a process for preparing terpinene-4-ol from limonene-4-ol via a hydrogenation reaction in the presence of a nickel catalyst.
Biotransformations of terpenes by fungi from amazonian Citrus plants
Moreno Rueda, Maria Gabriela,Guerrini, Alessandra,Giovannini, Pier Paolo,Medici, Alessandro,Grandini, Alessandro,Sacchetti, Gianni,Pedrini, Paola
, p. 1909 - 1919 (2013/11/06)
The biotransformations of (RS)-linalool (1), (S)-citronellal (2), and sabinene (3) with fungi isolated from the epicarp of fruits of Citrus genus of the Amazonian forest (i.e., C. limon, C. aurantifolia, C. aurantium, and C. paradisiaca) are reported. The
Cloning and characterization of Pfl-1841, a 2-methylenebornane synthase in Pseudomonas fluorescens PfO-1
Chou, Wayne K.W.,Ikeda, Haruo,Cane, David E.
supporting information; experimental part, p. 6627 - 6632 (2011/10/04)
The pfl-1841 gene from Pseudomonas fluorescens PfO-1 is the only gene in any of the three sequenced genomes of the Gram-negative bacterium P. fluorescens, that is, annotated as a putative terpene synthase. The predicted Pfl-1841 protein, which harbors the two strictly conserved divalent metal binding domains found in all terpene cyclases, is closely related to several known or presumed 2-methylisoborneol synthases, with the closest match being to the MOL protein of Micromonaspora olivasterospora KY11048 that has been implicated as a 2-methylenebornane synthase. A synthetic gene encoding P. fluorescens Pfl-1841 and optimized for expression in Escherichia coli was expressed and purified as an N-terminal His6-tagged protein. Incubation of recombinant Pfl-1841 with 2-methylgeranyl diphosphate produced 2-methylenebornane as the major product accompanied by 1-methylcamphene as well as other minor, monomethyl-homomonoterpene hydrocarbons and alcohols. The steady-state kinetic parameters for the Pfl-1841-catalyzed reaction were K M=110±13 nM and kcat=2.4±0.1×10 -2 s-1. Attempts to identify the P. fluorescens SAM-dependent 2-methylgeranyl diphosphate synthase have so far been unsuccessful.
A facile method for the rapid and selective deprotection of methoxymethyl (MOM) ethers
Han, Jae Hyun,Kwon, Young Eun,Sohn, Jeong-Hun,Ryu, Do Hyun
experimental part, p. 1673 - 1677 (2010/04/04)
We describe a rapid and efficient method for selective deprotection of methoxymethyl (MOM) ethers using ZnBr2 and n-PrSH, which completely removed MOM from diverse MOM ethers of primary, secondary, and tertiary alcohols or phenol derivatives. The deprotection takes less than ten minutes with both high yield and selectivity in the presence of other protecting groups. In addition, the rapid deprotection of MOM ethers of tertiary hydroxyls in high yield with no epimerization allows MOM to be a suitable protecting group for tertiary alcohols.
Lithium-potassium superbases as key reagents for the base-catalysed isomerisation of some terpenoids
Deagostino,Tivola,Prandi,Venturello
, p. 2856 - 2860 (2007/10/03)
Some representative monoterpenes have been isomerised under the influence of Schlosser's lithium-potassium mixed superbases, promoting β-elimination reactions. The results are compared with those obtained with butyllithium and LDA. Different selectivities and different reaction yields are achieved as a function of the base employed. These results confirm the particular reactivity of bimetallic reagents. In this paper it is proposed that the observed selectivities might depend on the conformational features of the substrate, on the strength of the organometallic reagent, as well as on steric requirements of the elimination reaction.
Base-catalysed rearrangement of p-menth-1-en-4(8)-oxide
Roy, Animesh,Gurudutt, K. N.,Rao, Sanjay
, p. 636 - 638 (2007/10/03)
p-Menth-1-en-4(8)-oxide (1), a tetrasubstituted spiro epoxide is normally resistant towards bases but under forcing condition with AIP rearranges to p-mentha-1,8-dien-4-ol (2).On the other hand, with t-BuOK, p-mentha-1,3-dien-8-ol (3) and p-mentha-1,4-dien-8-ol (4) are formed as the major products.These compounds readily get oxidised to p-cymen-8-ol (5), as seen in the reaction of 1 with N-LiEDA.
