Many terpenes are derived commercially from conifer resins, such as those made by this pine.
Terpenes (/ˈtɜːrpiːn/) are a class of natural products consisting of compounds with the formula (C5H8)n. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. Terpenes are further classified by the number of carbons: monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), etc. A well known monoterpene is alpha-pinene, a major component of turpentine.
History and terminology
The term "terpene" was coined in 1866 by the German chemist August Kekulé. The name "terpene" is a shortened form of "terpentine", an obsolete spelling of "turpentine".
Although sometimes used interchangeably with "terpenes", terpenoids (or isoprenoids) are modified terpenes that contain additional functional groups, usually oxygen-containing. The terms terpenes and terpenoids are used interchangeably by some. Both have strong and often pleasant odors, which may protect their hosts or attract pollinators. The inventory of terpenes and terpenoids is estimated at 55,000 chemical entities.
Higher amounts of terpenes are released by trees in warmer weather, where they may function as a natural mechanism of cloud seeding. The clouds reflect sunlight, allowing the forest temperature to regulate.
Structure of natural rubber, exhibiting the characteristic methyl group on the alkene group.
The one terpene that has major applications is natural rubber (i.e. polyisoprene). The possibility that other terpenes could be used as precursors to produce synthetic polymers has been investigated as an alternative to the use of petroleum-based feedstocks. However, few of these applications have been commercialized. Many other terpenes, however, have smaller scale commercial and industrial applications. For example, turpentine, a mixture of terpenes (e.g. pinene), obtained from the distillation of pine tree resin, is used as an organic solvent and as a chemical feedstock (mainly for the production of other terpenoids).Rosin, another by-product of conifer tree resin, is widely used as an ingredient in a variety of industrial products, such as inks, varnishes and adhesives. Terpenes are widely used as fragrances and flavors in consumer products such as perfumes, cosmetics and cleaning products, as well as food and drink products. For example, the aroma and flavor of hops comes, in part, from sesquiterpenes (mainly α-humulene and β-caryophyllene), which affect beer quality. Some form hydroperoxides that are valued as catalysts in the production of polymers.
Reflecting their defensive role, terpenes are used as active ingredients of natural pesticides in agriculture.
Many terpenes have been shown to have significant pharmacological effects, although most studies have been either in vitro, or in rats or mice; clinical studies in humans are very limited. Terpenes are also components of some traditional medicines, such as aromatherapy. Terpenes (and terpenoids) are prevalent in cannabis (marijuana) and have been postulated to modulate the medicinal or psychological effects of cannabinoids (e.g., THC or CBD) in humans; this is often referred to as the "entourage effect". However, there is currently little experimental data supporting this hypothesis.
Physical and chemical properties
Terpenes are colorless, although impure samples are often yellow. Boiling points scale with molecular size: terpenes, sesquiterpenes, and diterpenes respectively at 110, 160, and 220 °C. Being highly non-polar, they are insoluble in water. Being hydrocarbons, they are highly flammable and have low specific gravity (float on water).
Terpenoids (mono-, sesqui-, di-, etc.) have similar physical properties but tend to be more polar and hence slightly more soluble in water and somewhat less volatile than their terpene analogues. Highly polar derivative of terpenoids are the glycosides, which are linked to sugars. They are water-soluble solids. They are tactilely light oils considerably less viscous than familiar vegetable oils like corn oil (28 cP), with viscosity ranging from 1 cP (ala water) to 6 cP. Like other hydrocarbons, they are highly flammable. Terpenes are local irritants and can cause gastrointestinal disturbances if ingested.
The 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway (MEP/DOXP pathway), also known as non-mevalonate pathway or mevalonic acid-independent pathway, starts with pyruvate as the carbon source.
Pyruvate and glyceraldehyde 3-phosphate are converted by DOXP synthase (Dxs) to 1-deoxy-D-xylulose 5-phosphate, and by DOXP reductase (Dxr, IspC) to 2-C-methyl-D-erythritol 4-phosphate (MEP). The subsequent three reaction steps catalyzed by 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase (YgbP, IspD), 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (YchB, IspE), and 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (YgbB, IspF) mediate the formation of 2-C-methyl-D-erythritol 2,4-cyclopyrophosphate (MEcPP). Finally, MEcPP is converted to (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) by HMB-PP synthase (GcpE, IspG), and HMB-PP is converted to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) by HMB-PP reductase (LytB, IspH).
In both MVA and MEP pathways, IPP is isomerized to DMAPP by the enzyme isopentenyl pyrophosphate isomerase. IPP and DMAPP condense to give geranyl pyrophosphate, the precursor to monoterpenes and monoterpenoids.
The genomes of 17 plant species contain genes that encode terpenoid synthase enzymes imparting terpenes with their basic structure, and cytochrome P450s that modify this basic structure.
Terpenes can be visualized as the result of linking isoprene (C5H8) units "head to tail" to form chains and rings. A few terpenes are linked “tail to tail”, and larger branched terpenes may be linked “tail to mid”.
Strictly speaking all monoterpenes have the same chemical formula C10H16. Similarly all sesquiterpenes and diterpenes have formulas of C15H24 and C20H32 respectively. The structural diversity of mono-, sesqui-, and diterpenes is a consequence of isomerism.
Terpenes and terpenoids are usually chiral. Chiral compounds can exist as non-superimposable mirror images, which exhibit distinct physical properties such as odor or toxicity.
Most terpenes and terpenoids feature C=C groups, i.e. they exhibit unsaturation. Since they carry no functional groups aside from their unsaturation, terpenes are structurally distinctive. The unsaturation is associated with di- and trisubstituted alkenes. Di- and trisubstituted alkenes resist polymerization (low ceiling temperatures) but are susceptible to acid-induced carbocation formation.
Terpenes may be classified by the number of isoprene units in the molecule; a prefix in the name indicates the number of isoprene pairs needed to assemble the molecule. Commonly, terpenes contain 2, 3, 4 or 6 isoprene units; the tetraterpenes (8 isoprene units) form a separate class of compounds called carotenoids; the others are rare.
Hemiterpenes consist of a single isoprene unit. Isoprene itself is the only hemiterpene, but oxygen-containing derivatives such as prenol and isovaleric acid are hemiterpenoids.
Sesquarterpenes are composed of seven isoprene units and have the molecular formula C35H56. Sesquarterpenes are typically microbial in their origin. Examples of sesquarterpenoids are ferrugicadiol and tetraprenylcurcumene.
Polyterpenes consist of long chains of many isoprene units. Natural rubber consists of polyisoprene in which the double bonds are cis. Some plants produce a polyisoprene with trans double bonds, known as gutta-percha.
While terpenes and terpenoids occur widely, their extraction from natural sources is often problematic. Consequently, they are produced by chemical synthesis, usually from petrochemicals. In one route, acetone and acetylene are condensed to give 2-Methylbut-3-yn-2-ol, which is extended with acetoacetic ester to give geranyl alcohol. Others are prepared from those terpenes and terpenoids that are readily isolated in quantity, say from the paper and tall oil industries. For example, α-pinene, which is readily obtainable from natural sources, is converted to citronellal and camphor. Citronellal is also converted to rose oxide and menthol.
Summary of an industrial route to geranyl alcohol from simple reagents.
^ abcdeDavis, Edward M.; Croteau, Rodney (2000). "Cyclization enzymes in the biosynthesis of monoterpenes, sesquiterpenes, and diterpenes". Biosynthesis. Topics in Current Chemistry. 209. pp. 53–95. doi:10.1007/3-540-48146-X_2. ISBN978-3-540-66573-1.CS1 maint: uses authors parameter (link)
^Kekulé coined the term "terpene" to denote all hydrocarbons having the empirical formula C10H16, of which camphene was one. Previously, many hydrocarbons having the empirical formula C10H16 had been called "camphene", but many other hydrocarbons of the same composition had had different names. Hence Kekulé coined the term "terpene" in order to reduce the confusion.
Kekulé, August (1866). Lehrbuch der organischen Chemie [Textbook of Organic Chemistry] (in German). vol. 2. Erlangen, (Germany): Ferdinand Enke. pp. 464–465. |volume= has extra text (help) From pp. 464–465: "Mit dem Namen Terpene bezeichnen wir … unter verschiedenen Namen aufgeführt werden." (By the name "terpene" we designate in general the hydrocarbons composed according to the [empirical] formula C10H16 (see §. 1540). Many chemists subsume the hydrocarbons of the formula C10H16 under the general name "camphene". That name seems unsuitable, because a specific substance of this group has been designated as "camphene". In general, a great confusion prevails in the designation of substances belonging here [i.e., to the terpene group]. Many, obviously different hydrocarbons have not been distinguished for a long time and have been assigned the same names, while on the other hand, probably identical substances from different sources have often been specified by different names.)
Dev, Sukh (1989). "Chapter 8. Isoprenoids: 8.1. Terpenoids.". In Rowe, John W. (ed.). Natural Products of Woody Plants: Chemicals Extraneous to the Lignocellulosic Cell Wall. Berlin and Heidelberg, Germany: Springer-Verlag. pp. 691–807. ; see p. 691.
^Steenackers, B.; De Cooman, L.; De Vos, D. (2015). "Chemical transformations of characteristic hop secondary metabolites in relation to beer properties and the brewing process: A review". Food Chemistry. 172: 742–756. doi:10.1016/j.foodchem.2014.09.139. PMID25442616.
^Eschenmoser, Albert; Arigoni, Duilio (December 2005). "Revisited after 50 Years: The 'Stereochemical Interpretation of the Biogenetic Isoprene Rule for the Triterpenes'". Helvetica Chimica Acta. 88 (12): 3011–3050. doi:10.1002/hlca.200590245.
^Kumari, I.; Ahmed, M.; Akhter, Y. (2017). "Evolution of catalytic microenvironment governs substrate and product diversity in trichodiene synthase and other terpene fold enzymes". Biochimie. 144: 9–20. doi:10.1016/j.biochi.2017.10.003. PMID29017925.
^Günata, Z.; Wirth, J. L.; Guo, W.; Baumes, R. L. (2001). Carotenoid-Derived Aroma Compounds; chapter 13: Norisoprenoid Aglycon Composition of Leaves and Grape Berries from Muscat of Alexandria and Shiraz Cultivars. ACS Symposium Series. 802. pp. 255–261. doi:10.1021/bk-2002-0802.ch018. ISBN978-0-8412-3729-2.
^Zelena, K.; Hardebusch, B.; Hülsdau, B.; Berger, R. G.; Zorn, H. (2009). "Generation of Norisoprenoid Flavors from Carotenoids by Fungal Peroxidases". Journal of Agricultural and Food Chemistry. 57 (21): 9951–9955. doi:10.1021/jf901438m. PMID19817422.
^Cabaroğlu, T.; Selli, S.; Canbaş, A.; Lepoutre, J.-P.; Günata, Z. (2003). "Wine flavor enhancement through the use of exogenous fungal glycosidases". Enzyme and Microbial Technology. 33 (5): 581–587. doi:10.1016/S0141-0229(03)00179-0.
Pope, Frank George (1911). "Terpenes" . In Chisholm, Hugh (ed.). Encyclopædia Britannica. 26 (11th ed.). Cambridge University Press. pp. 647–652. This contains a detailed survey of the chemistry of many terpenes, which had recently been investigated fully.