Terpinen-4-ol CAS 562-74-3 Basic information
|Product Categories:||Biochemistry;Terpenes;Terpenes (Others);Monocyclic Monoterpenes;Intermediates & Fine Chemicals;Pharmaceuticals;Alphabetical Listings;C-DFlavors and Fragrances;Certified Natural Products;Flavors and Fragrances;C-D|
Terpinen-4-ol CAS 562-74-3 Chemical Properties
|Melting point:||137-188 °C|
|Boiling point:||212 °C|
|Water Solubility:||Very slightly soluble|
|color:||Clear colorless to slightly yellow|
|refractive index:||n20/D 1.478|
|Stability:||Stable. Combustible. Incompatible with strong oxidizing agents.|
|Specific Gravity:||0.930.9265 (19℃)|
|FEMA:||2248 | 4-CARVOMENTHENOL|
|optical activity:||[α]20/D 27°, neat|
|CAS DataBase Reference:||562-74-3(CAS DataBase Reference)|
|EPA Substance Registry System:||4-Terpineol (562-74-3)|
Colorless to yellowish slightly viscous liquid 无色至微黄色稍粘稠液体
The pleasant smell of nutmeg
|Terpinen-4-ol Usage And Synthesis|
|Overview||Essential oils and their components extracted from vegetable materials have been found to exhibit anti-microbial, anti-viral, anti-fungal, anti-oxidant, anti-inflammatory and anti-cancer activities[1–3].|
Monoterpenes are major plant-derived secondary metabolites widely found in natural products, including fruits, vegetables and herbs and known to be associated with the plant defense mechanisms. The monoterpenes consist of two isoprene units, and are found in large amounts in essential oils[4,5]. In addition, many monoterpenes have been proposed to exert potent anticancer activity. Some of them reportedly displayed promising results in the prevention and treatment of different types of leukemia and cancers, such as breast, skin, pancreatic and colon cancers in rodents. Notably, several of these compounds, among them Perillyl alcohol and limonene, are being testing in ongoing human studies[7–9].
Terpinen-4-ol, one of the primary active ingredients of the tea tree oil (TTO), consists of a mixture of more than 100 different compounds, and is found in a variety of aromatic plants (oranges, mandarins, origanum, New Zealand lemonwood tree, Japanese cedarand black pepper).
Terpinen-4-ol is a potent bactericidal agent that possesses antifungal properties. Of particular interest is in vitro activity against Staphylococcus aureus and C. albicans[13,14]. It was shown that combining this natural substance and conventional drugs may help treat resistant yeast and bacterial infections.
Several recent reports have suggested that terpinen-4-ol induces 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[15,16]. Moreover, terpinen-4-ol was shown to elicit a dose-dependent cytotoxic response on human non-small cell lung cancer cells, presumably through the involvement of the mitochondrial apoptotic pathway.
Figure 1 the chemical structure of Terpinen-4-ol;
|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.|
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. 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, several groups have evaluated the activity of TTO against MRSA, beginning with Carson et al. 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. Electron microscopy of terpinen-4-ol-treated S. aureus cells revealed lesions similar to those seen after TTO treatment, 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.
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. 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. Further investigation showed that terpinen-4-ol contributed significantly to this 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.
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. 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 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. Work has now shown that terpinen-4-ol modulates the vasodilation and plasma extravasation associated with histamine-induced inflammation in humans.
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.
|Chemical Properties||colourless or pale yellow liquid|
|Chemical Properties||1-Terpinen-4-ol occurs as (+)-, (?)-, and racemic 1-terpinen-4-ol in many essential oils, for example, from Pinus and Eucalyptus species, and in lavender oil. It is a colorless liquid with a spicy, nutmeg-like, woody–earthy, and also lilac-like odor.|
1-Terpinen-4-ol is a by-product in the synthesis of terpineol fromterpin hydrate and occurs in commercial terpineol. Pure 1-terpinen-4-ol can be prepared from terpinolene by photosensitized oxidation, reduction of the resulting 1-methyl-4- isopropenyl-1-cyclohexene-4-hydroperoxide, and selective hydrogenation of the corresponding alcohol.
It is used, for example, in artificial geranium and pepper oils and in perfumery for creating herbaceous and lavender notes.
|Occurrence||4-Carvomenthenol (dextro) has been reported present in the oil of Cupressus macrocarpa lavender, Spanish origanum, Ledum palustre, Eucalyptus australiana var. A., Thuja occidentalis, etc. The l-form is present in the oil of Eucalyptus dives and in some other essences such as Xanthoxylum rhetsa, together with the racemic form. The racemic form is found in camphor oil. Reported found in fresh apple, apricots, orange juice, peel oils of orange, lemon, grapefruit, tangerines, anise, cinnamon, ginger and nutmeg.|
|Uses||Shows antioxidant effects. Antiseptic.|
|Definition||ChEBI: A terpineol that is 1-menthene carrying a hydroxy substituent at position 4.|
|Taste threshold values||Taste characteristics at 30 ppm: sweet, citrus green with a tropical fruity character.|
|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).|
|Chemical 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).|