Caryophyllene

Caryophyllene

Names
IUPAC names 4,11,11-trimethyl-8-methylene- bicyclo[7.2.0]undec-4-ene
Other names β-Caryophyllene; trans-(1R,9S)-8-Methylene-4,11,11-trimethylbicyclo[7.2.0]undec-4-ene
Identifiers
CAS Number	87-44-5
ChEBI	CHEBI:10357
ChEMBL	ChEMBL445740
ChemSpider	4444848
Jmol 3D model	Interactive image
PubChem	5281515
UNII	BHW853AU9H
InChI InChI=1S/C15H24/c1-11-6-5-7-12(2)13-10-15(3,4)14(13)9-8-11/h6,13-14H,2,5,7-10H2,1,3-4H3/b11-6+/t13-,14-/m1/s1 Key: NPNUFJAVOOONJE-GFUGXAQUSA-N InChI=1/C15H24/c1-11-6-5-7-12(2)13-10-15(3,4)14(13)9-8-11/h6,13-14H,2,5,7-10H2,1,3-4H3/b11-6+/t13-,14-/m1/s1 Key: NPNUFJAVOOONJE-GFUGXAQUBC
SMILES C1(=C)\CC/C=C(/CC[C@@H]2[C@@H]1CC2(C)C)C
Properties
Chemical formula	C15H24
Molar mass	204.36 g·mol^−1
Density	0.9052 g/cm^3 (17 °C)[1]
Boiling point	254–257 °C (489–495 °F; 527–530 K)[2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Caryophyllene /ˌkærioʊfɪˈliːn/, or (−)-β-caryophyllene, is a natural bicyclic sesquiterpene that is a constituent of many essential oils, especially clove oil, the oil from the stems and flowers of Syzygium aromaticum (cloves),^[3] the essential oil of hemp Cannabis sativa,^[4] rosemary Rosmarinus officinalis,^[5] and hops.^[6] It is usually found as a mixture with isocaryophyllene (the cis double bond isomer) and α-humulene (obsolete name: α-caryophyllene), a ring-opened isomer. Caryophyllene is notable for having a cyclobutane ring, as well as a trans-double bond in an 8-membered ring, both rarities in nature.

Caryophyllene is one of the chemical compounds that contributes to the spiciness of black pepper. Beta-caryophyllene was shown to be selective agonist of cannabinoid receptor type-2 (CB₂) and to exert significant cannabimimetic antiinflammatory effects in mice.^[4] Antinociceptive,^[7] neuroprotective,^[8] anxiolytic and antidepressant ^[9] and anti-alcoholism ^[10] activity have been uncovered. Because the widespread plant natural product beta-caryophyllene is an FDA approved food additive and ingested daily with food it is the first dietary cannabinoid. Whether this compound is able to modulate inflammatory processes in humans via the endocannabinoid system is yet unknown. Beta-caryophyllene does not bind to the centrally expressed cannabinoid receptor type-1 (CB₁) and therefore does not exert psychoactive effects.

The first total synthesis of caryophyllene in 1964 by E.J. Corey was considered one of the classic demonstrations of the possibilities of synthetic organic chemistry at the time.^[11]

Caryophyllene oxide, in which the olefin of caryophyllene has become an epoxide, is the component responsible for cannabis identification by drug-sniffing dogs^[12][13] and is also an approved food flavoring.^[14]

Natural sources

The approximate quantity of caryophyllene in the essential oil of each source is given in square brackets ([ ]):

• Cannabis, hemp, marijuana (Cannabis sativa)^[4] [3.8–37.5% of cannabis flower essential oil]^[15]
• Black Caraway (Carum nigrum) [7.8%]^[16]
• Cloves (Syzygium aromaticum)^[3] [1.7%-19,5% of clove bud essential oil]^[17][18]
• Hops (Humulus lupulus)^[19] [5.1–14.5%]^[20]
• Basil (Ocimum spp.)^[21] [5.3–10.5% O. gratissimum; 4.0–19.8% O. micranthum]^[22]
• Oregano (Origanum vulgare)^[23] [4.9%-15.7]^[24][25]
• Black pepper (Piper nigrum) [7.29%]^[26]
• West African Pepper (Piper guineense) [57.59% (black); 51.75% (white)]^[26]
• Lavender (Lavandula angustifolia) [4.62% of lavender oil]^[27]
• Rosemary (Rosmarinus officinalis)^[5] [0.1–8.3%]^[28]
• True cinnamon (Cinnamomum zeylanicum) [6.9–11.1%]^[29]
• Malabathrum (Cinnamomum tamala) [25.3%]^[30]
• Cananga odorata [3.1%-10.7%]^[31]
• Copaiba oil (Copaifera spp.) ^{[32][33][34][35]}

Compendial status

• Food Chemicals Codex^[36][37]

Notes and references

1. SciFinder Record, CAS Registry Number 87-44-5
2. Baker, Richard R. (2004). "The pyrolysis of tobacco ingredients". Journal of Analytical and Applied Pyrolysis 71 (1): 223–311. doi:10.1016/s0165-2370(03)00090-1.
3. Ghelardini C, Galeotti N, Di Cesare Mannelli L, Mazzanti G, Bartolini A (2001). "Local anaesthetic activity of beta-caryophyllene". Farmaco 56 (5–7): 387–9. doi:10.1016/S0014-827X(01)01092-8. PMID 11482764.
4. Gertsch J, Leonti M, Raduner S; et al. (July 2008). "Beta-caryophyllene is a dietary cannabinoid". Proceedings of the National Academy of Sciences of the United States of America 105 (26): 9099–104. doi:10.1073/pnas.0803601105. PMC 2449371. PMID 18574142.
5. Ormeño E, Baldy V, Ballini C, Fernandez C (September 2008). "Production and diversity of volatile terpenes from plants on calcareous and siliceous soils: effect of soil nutrients". J. Chem. Ecol. 34 (9): 1219–29. doi:10.1007/s10886-008-9515-2. PMID 18670820.
6. Glenn Tinseth, "Hop Aroma and Flavor", January/February 1993, Brewing Techniques. <http://realbeer.com/hops/aroma.html> Accessed July 21, 2010.
7. Katsuyama S., Mizoguchi H., Kuwahata H.; et al. (2013). "Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception". European journal of pain 17 (5): 664–675. doi:10.1002/j.1532-2149.2012.00242.x.
8. Guimarães-Santos, Adriano (2012). "Copaiba Oil-Resin Treatment Is Neuroprotective and Reduces Neutrophil Recruitment and Microglia Activation after Motor Cortex Excitotoxic Injury". Evidence-Based Complementary and Alternative Medicine 2012: 1–9. doi:10.1155/2012/918174. PMC 3291111. PMID 22461843.
9. Bahi Amine, Al Mansouri Shamma, Al Memari Elyazia, Al Ameri Mouza, Nurulain Syed M., Ojha Shreesh. (2014). "β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice.". Physiology & Behavior 135: 119–124. doi:10.1016/j.physbeh.2014.06.003.
10. Al Mansouri Shamma, Ojha Shreesh, Al Maamari Elyazia, Al Ameri Mouza, Nurulain Syed M., Bahi Amine. (2014). "The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice.". Pharmacology, biochemistry, and behavior. 2014;124C:260-268 124: 260–268. doi:10.1016/j.pbb.2014.06.025.
11. Corey EJ, Mitra RB, Uda H (1964). "Total Synthesis of d,l-Caryophyllene and d,l-Isocaryophyllene". Journal of the American Chemical Society 86 (3): 485–492. doi:10.1021/ja01057a040.
12. Ethan (2011). "Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects". Br J Pharmacol 163 (7): 1344–1364. doi:10.1111/j.1476-5381.2011.01238.x. PMC 3165946. PMID 21749363.
13. Stahl, E; Kunde, R (1973). "Die Leitsubstanzen der Haschisch-Suchhunde". Kriminalistik: Z Gesamte Kriminal Wiss Prax. 27: 385–389.
14. http://www.thegoodscentscompany.com/data/rw1023631.html
15. Mediavilla, Vito; Simon Steinemann. "Essential oil of Cannabis sativa L. strains". International Hemp Association. Retrieved 11 July 2008.
16. Singh G, Marimuthu P, de Heluani CS, Catalan CA (January 2006). "Antioxidant and biocidal activities of Carum nigrum (seed) essential oil, oleoresin, and their selected components". J. Agric. Food Chem. 54 (1): 174–81. doi:10.1021/jf0518610. PMID 16390196.
17. Alma, M. Hakkı; Ertaş, Murat; Nitz, Siegfrie; Kollmannsberger, Hubert (May 2007). Lucia, Lucian A.; Hubbe, Martin A., eds. "Chemical composition and content of essential oil from the bud of cultivated Turkish clove" (PDF). BioResources (Raleigh, North Carolina, USA: North Carolina State University) 2 (2): 265–269. ISSN 1930-2126. Retrieved September 6, 2010. The results showed that the essential oils mainly contained about [...] 3.56% β-Caryophyllene
18. Clove Essential Oil
19. Wang G, Tian L, Aziz N; et al. (November 2008). "Terpene Biosynthesis in Glandular Trichomes of Hop". Plant Physiol. 148 (3): 1254–66. doi:10.1104/pp.108.125187. PMC 2577278. PMID 18775972.
20. Bernotienë, Genovaitë; Nivinskienë, Ona; Butkienë, Rita; Mockutë, Danutë (2004). "Chemical composition of essential oils of hops (Humulus lupulus L.) growing wild in Auktaitija" (PDF). Chemija. 2 (Vilnius, Lithuania: Lithuanian Academy of Sciences) 4: 31–36. ISSN 0235-7216. Retrieved September 6, 2010.
21. Zheljazkov VD, Cantrell CL, Tekwani B, Khan SI (January 2008). "Content, composition, and bioactivity of the essential oils of three basil genotypes as a function of harvesting". J. Agric. Food Chem. 56 (2): 380–5. doi:10.1021/jf0725629. PMID 18095647.
22. Silva, Maria Goretti de Vasconcelos; Matos, Francisco José de Abreu; Lopes, Paulo Roberto Oliveira; Silva, Fábio Oliveira; Holanda, Márcio Tavares (August 2, 2004). Cragg, Gordon M.; Bolzani, Vanderlan S.; Rao, G. S. R. Subba, eds. "Composition of essential oils from three Ocimum species obtained by steam and microwave distillation and supercritical CO₂ extraction" (PDF). Arkivoc (ARKAT USA, Inc.) 2004 (vi): 66–71. doi:10.3998/ark.5550190.0005.609. ISSN 1424-6376. Retrieved September 6, 2010.
23. Harvala C, Menounos P, Argyriadou N (February 1987). "Essential Oil from Origanum dictamnus". Planta Med. 53 (1): 107–9. doi:10.1055/s-2006-962640. PMID 17268981.
24. Calvo-Irabien, L. M.; Yam-Puc, J. A.; Dzib, G.; Escalante-Erosa, F.; Peña-Rodriguez, L. M. (July 2009). "Effect of Postharvest Drying on the Composition of Mexican Oregano (Lippia graveolens) Essential Oil". Journal of Herbs, Spices & Medicinal Plants (London, UK: Taylor & Francis) 15 (3): 281–287. doi:10.1080/10496470903379001. ISSN 1540-3580.
25. The essential oil of Origanum vulgare L. ssp. vulgare growing wild in vilnius district (Lithuania) Phytochemistry. 2001 May;57(1):65-9.
26. Jirovetz L, Buchbauer G, Ngassoum MB, Geissler M (November 2002). "Aroma compound analysis of Piper nigrum and Piper guineense essential oils from Cameroon using solid-phase microextraction-gas chromatography, solid-phase microextraction-gas chromatography-mass spectrometry and olfactometry". J Chromatogr A 976 (1–2): 265–75. doi:10.1016/S0021-9673(02)00376-X. PMID 12462618.
27. A. Prashar, I. C. Locke, C. S. Evans (2004). Cytotoxicity of lavender oil and its major components to human skin cells. Cell Proliferation 37 (3), 221–229.
28. Jamshidi, R.; Afzali, Z.; Afzali, D. (February 2009). "Chemical Composition of Hydrodistillation Essential Oil of Rosemary in Different Origins in Iran and Comparison with Other Countries" (PDF). American-Eurasian Journal of Agricultural & Environmental Sciences (Pakistan: IDOSI Publications) 5 (1): 78–81. ISSN 1990-4053. Retrieved September 6, 2010.
29. Kaul PN, Bhattacharya AK, Rao BRR; et al. (2003). "Volatile constituents of essential oils isolated from different parts of cinnamon (Cinnamomum zeylanicum Blume)". Journal of the Science of Food and Agriculture 83 (1): 53–55. doi:10.1002/jsfa.1277.
30. Ahmed A, Choudhary MI, Farooq A; et al. (2000). "Essential oil constituents of the spice Cinnamomum tamala (Ham.) Nees & Eberm.". Flavour and Fragrance Journal 15 (6): 388–390. doi:10.1002/1099-1026(200011/12)15:6<388::AID-FFJ928>3.0.CO;2-F.
31. Ylang Ylang Essential Oil
32. "Chemistry and biological activities of terpenoids from copaiba (Copaifera spp.) oleoresins.". Molecules 17 (4): 3866–89. 2012. doi:10.3390/molecules17043866. PMID 22466849.
33. "Validation of a gas chromatographic method to quantify sesquiterpenes in copaiba oils.". J Pharm Biomed Anal 54 (4): 653–9. Mar 2011. doi:10.1016/j.jpba.2010.10.006. PMID 21095089.
34. http://staff.najah.edu/sites/default/files/Within_plant_distribution_and_emission_of_sesquiterpenes_from_Copaifera_officinalis.pdf
35. http://www.rain-tree.com/copaiba.htm
36. The United States Pharmacopeial Convention. "Revisions to FCC, First Supplement". Retrieved 29 June 2009.
37. Therapeutic Goods Administration. "Chemical substances" (PDF). Retrieved 29 June 2009.