Many terpenes are derived commercially from conifer resins, such as those made by thispine.
Terpenes (/ˈtɜːrpiːnz/TUR-peenz) are a large and diverse class ofnatural products with the general formula(C5H8)n, wheren ≥ 2. They serve as crucial biosynthetic building blocks in many organisms, particularly plants. Comprising more than 30,000 compounds, these unsaturatedhydrocarbons are produced predominantly byplants, particularlyconifers.[1][2][3] In plants, terpenes and terpenoids are important mediators of ecologicalinteractions, while some insects use some terpenes as a form of defense. Other functions of terpenoids include cell growth modulation and plant elongation, light harvesting and photoprotection, and membrane permeability and fluidity control.
One terpene that has major applications isnatural rubber (i.e.,polyisoprene). The possibility that other terpenes could be used as precursors to produce syntheticpolymers has been investigated. Many terpenes have been shown to have pharmacological effects. Terpenes are also components of some traditional medicines, such asaromatherapy, and as active ingredients ofpesticides in agriculture.[4]
The termTerpen (German) was coined in 1866 by the German chemistAugust Kekulé to denote all hydrocarbons having the empirical formula C10H16, of whichcamphene was one. Previously, many hydrocarbons having the empirical formula C10H16 had been called "camphene", but many other hydrocarbons of the same composition had different names. Kekulé coined the term "Terpen" in order to reduce the confusion.[5][6] The name is a shortened form of "Terpentin", the german word for "turpentine".[7]
Although sometimes used interchangeably with "terpenes",terpenoids (orisoprenoids) are modified terpenes that contain additionalfunctional groups, usually oxygen-containing.[8] The terms terpenes and terpenoids are often used interchangeably, however. Furthermore, terpenes are produced from terpenoids and many terpenoids are produced from terpenes. Both have strong and often pleasant odors, which may protect their hosts or attract pollinators. The number of terpenes and terpenoids is estimated at 55,000 chemical entities.[9]
Terpenes are major biosynthetic building blocks.Steroids, for example, are derivatives of the triterpenesqualene. Terpenes and terpenoids are also the primary constituents of theessential oils of many types of plants and flowers.[13] In plants, terpenes and terpenoids are important mediators of ecologicalinteractions. For example, they play a role inplant defense against herbivory,disease resistance, attraction ofmutualists such aspollinators, as well as potentially plant-plant communication.[14][15] They appear to play roles asantifeedants.[2] Other functions of terpenoids include cell growth modulation and plant elongation, light harvesting and photoprotection, and membrane permeability and fluidity control.[16]
Higher amounts of terpenes are released by trees in warmer weather,[17] where they may function as a natural mechanism ofcloud seeding. The clouds reflect sunlight, allowing the forest temperature to regulate.[18]
Structure of natural rubber, exhibiting the characteristic methyl group on the alkene group
One terpene that has major applications isnatural rubber (i.e.,polyisoprene). The possibility that other terpenes could be used as precursors to produce syntheticpolymers has been investigated as an alternative to the use of petroleum-based feedstocks. However, few of these applications have been commercialized.[20] 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 treeresin, is used as an organicsolvent and as a chemical feedstock (mainly for the production of other terpenoids).[7]Rosin, another by-product of conifer tree resin, is widely used as an ingredient in a variety of industrial products, such asinks,varnishes andadhesives. Rosin is also used by violinists (and players of similarbowed instruments) to increase friction on thebow hair, byballet dancers on the soles of their shoes to maintain traction on the floor, bygymnasts to keep their grips while performing, and bybaseball pitchers to improve their control of the baseball.[21] Terpenes are widely used as fragrances and flavors in consumer products such asperfumes,cosmetics andcleaning products, as well as food and drink products. For example, the aroma and flavor ofhops comes, in part, fromsesquiterpenes (mainlyα-humulene andβ-caryophyllene), which affectbeer quality.[22] Some form hydroperoxides that are valued as catalysts in the production of polymers.
Many terpenes have been shown to have pharmacological effects, although most studies are from laboratory research, andclinical research in humans is preliminary.[23] Terpenes are also components of some traditional medicines, such asaromatherapy.[24]
Reflecting their defensive role in plants, terpenes are used as active ingredients ofpesticides in agriculture.[25]
Tetrahydrocannabinol, a terpenoid, not a terpene, is the active ingredient in marijuana.
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). They are tactilely light oils considerably lessviscous than familiar vegetable oils like corn oil (28cP), with viscosity ranging from 1 cP (à la water) to 6 cP. Terpenes are local irritants and can cause gastrointestinal disturbances if ingested.
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 derivatives of terpenoids are theglycosides, which are linked to sugars. These are water-soluble solids.
Conceptually derived fromisoprenes, the structures and formulas of terpenes follow thebiogenetic isoprene rule or theC5 rule, as described in 1953 byLeopold Ružička[26] and colleagues.[27] The C5 isoprene units are provided in the form ofdimethylallyl pyrophosphate (DMAPP) andisopentenyl pyrophosphate (IPP). DMAPP and IPP arestructural isomers to each other. This pair of building blocks are produced by two distinctmetabolic pathways: themevalonate (MVA) pathway and thenon-mevalonate (MEP) pathway. These two pathways are mutually exclusive in most organisms, except for some bacteria and land plants.[citation needed] In general, most archaea and eukaryotes use the MVA pathway, while bacteria mostly have the MEP pathway. IPP and DMAPP are final products of both MVA and MEP pathways and the relative abundance of these two isoprene units is enzymatically regulated in host organisms.
This pathway conjugates three molecules ofacetyl CoA.
The mevalonate (MVA) pathway is distributed in all three domains of life; archaea, bacteria and eukaryotes. The MVA pathway is universally distributed in archaea and non-photosynthetic eukaryotes, while the pathway is sparse in bacteria. In photosynthetic eukaryotes, some species possess the MVA pathway, while others have the MEP pathway or both MVA and MEP pathways. This is due to the acquisition of the MEP pathway by a common ancestor ofArchaeplastida (algae + land plants) through theendosymbiosis of ancestralcyanobacteria that possessed the MEP pathway. The MVA and MEP pathways were selectively lost in individual photosynthetic lineages.
Also, the archaeal MVA pathway is not completely homologous to the eukaryotic MVA pathway.[28] Instead, the eukaryotic MVA pathway is closer to the bacterial MVA pathway.
The non-mevalonate pathway or the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway starts withpyruvate andglyceraldehyde 3-phosphate (G3P) as the carbon source.
In both MVA and MEP pathways, IPP is isomerized to DMAPP by the enzyme isopentenyl pyrophosphate isomerase. IPP and DMAPP condense to givegeranyl pyrophosphate, the precursor to monoterpenes and monoterpenoids.
The genomes of many plant species contain genes that encode terpenoid synthase enzymes imparting terpenes with their basic structure, andcytochrome P450s that modify this basic structure.[2][31]
Terpenes can be visualized as the result of linkingisoprene (C5H8) units "head to tail" to form chains and rings.[32] 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 usuallychiral. Chiral compounds can exist as non-superposable mirror images, which exhibit distinctphysical 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 trisubstitutedalkenes. Di- and trisubstituted alkenes resist polymerization (lowceiling temperatures) but are susceptible to acid-inducedcarbocation 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.
The basic unit isoprene itself is a hemiterpene. It may form oxygen-containing derivatives such asprenol andisovaleric acid analogous to terpenoids.
Sesquiterpenes consist ofthree isoprene units and have the molecular formula C15H24. Examples of sesquiterpenes and sesquiterpenoids includehumulene,farnesenes,farnesol,geosmin.[34] (Thesesqui- prefix means one and a half.)
Sesterterpenes, terpenes having 25 carbons andfive isoprene units, are rare relative to the other sizes. (Thesester- prefix means two and a half.) An example of a sesterterpenoid isgeranylfarnesol.
Triterpenes consist ofsix isoprene units and have the molecular formula C30H48. The linear triterpenesqualene, the major constituent ofshark liver oil, is derived from the reductive coupling of two molecules offarnesyl pyrophosphate. Squalene is then processed biosynthetically to generate eitherlanosterol orcycloartenol, the structural precursors to all thesteroids.
Sesquarterpenes are composed ofseven isoprene units and have the molecular formula C35H56. Sesquarterpenes are typically microbial in their origin. Examples of sesquarterpenoids are ferrugicadiol and tetraprenylcurcumene.
Tetraterpenes containeight isoprene units and have the molecular formula C40H64. Biologically important tetraterpenoids include the acycliclycopene, the monocyclicgamma-carotene, and the bicyclicalpha- andbeta-carotenes.
Polyterpenes consist of long chains ofmany isoprene units. Naturalrubber consists of polyisoprene in which the double bonds arecis. Some plants produce a polyisoprene withtrans double bonds, known asgutta-percha.
Norisoprenoids, characterized by the shortening of a chain or ring by the removal of a methylene group or substitution of one or more methyl side chains by hydrogen atoms. These include the C13-norisoprenoid 3-oxo-α-ionol present inMuscat of Alexandria leaves and 7,8-dihydroionone derivatives, such as megastigmane-3,9-diol and 3-oxo-7,8-dihydro-α-ionol found inShiraz leaves (both grapes in the speciesVitis vinifera)[35] orwine[36][37] (responsible for some of thespice notes inChardonnay), can be produced by fungalperoxidases[38] orglycosidases.[39]
While terpenes and terpenoids occur widely, their extraction from natural sources is often problematic. Consequently, they are produced by chemical synthesis, usually frompetrochemicals. In one route,acetone andacetylene are condensed to give2-Methylbut-3-yn-2-ol, which is extended withacetoacetic ester to givegeranyl alcohol. Others are prepared from those terpenes and terpenoids that are readily isolated in quantity, say from the paper andtall oil industries. For example,α-pinene, which is readily obtainable from natural sources, is converted tocitronellal andcamphor. Citronellal is also converted torose oxide andmenthol.[1]
Summary of an industrial route to geranyl alcohol from simple reagents (wrong arrow. this is not a retrosynthesis)
^abcdeDavis, Edward M.; Croteau, Rodney (2000). "Cyclization enzymes in the biosynthesis of monoterpenes, sesquiterpenes, and diterpenes".Biosynthesis. Vol. 209. pp. 53–95.doi:10.1007/3-540-48146-X_2.ISBN978-3-540-66573-1.{{cite book}}:|journal= ignored (help)
^Stoker, H. Stephen (2007).General, Organic, and Biological Chemistry, 4th edition. Houghton Mifflin Company. p. 337.ISBN978-0-618-73063-6.
^Kekulé, August (1866).Lehrbuch der organischen Chemie [Textbook of Organic Chemistry] (in German). Vol. 2. Erlangen, (Germany): Ferdinand Enke. pp. 464–465.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)
^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. Heidelberg, Germany / Berlin: Springer-Verlag. pp. 691–807. ;see p. 691.
^Silvestre, Armando J.D.; Gandini, Alessandro (2008). "Terpenes: Major Sources, Properties and Applications".Monomers, Polymers and Composites from Renewable Resources. pp. 17–38.doi:10.1016/B978-0-08-045316-3.00002-8.ISBN9780080453163.
^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.Bibcode:2005HChAc..88.3011E.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.
^Ružička, Leopold (1953). "The isoprene rule and the Biogenesis of terpenic compounds".Cellular and Molecular Life Sciences.9 (10):357–367.doi:10.1007/BF02167631.PMID13116962.S2CID44195550.
^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. Vol. 802. pp. 255–261.doi:10.1021/bk-2002-0802.ch018.ISBN978-0-8412-3729-2.
^Vinholes, J.; Coimbra, M. A.; Rocha, S. M. (2009). "Rapid tool for assessment of C13 norisoprenoids in wines".Journal of Chromatography A.1216 (47):8398–8403.doi:10.1016/j.chroma.2009.09.061.PMID19828152.
^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.Bibcode:2009JAFC...57.9951Z.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.
