Humulene
Encyclopedia
Humulene, also known as α-humulene or α-caryophyllene, is a naturally occurring monocyclic sesquiterpene
, which is a terpenoid
consisting of 3 isoprene
units. It is found in the essential oil
s of Humulus lupulus
(hops
) from which it derives its name. It is an isomer
of β-caryophyllene
, and the two are often found together as a mixture in nature. It is also found in Lindera strychnifolia, and is one of the chemical compounds that contribute to the taste of the spice Vietnamese coriander
. It also contributes to the characteristic aroma of Cannabis sativa
, where it is present in the essential oil
of the plant.
This biosynthesis can be mimicked in the lab by preparing allylic stanane from farnesol, termed Corey synthesis. There are diverse ways to synthesize humulene in the laboratory, involving differing closures of the C-C bond in the macrocycle. The McMurry synthesis uses a titanium-catalyzed carbonyl coupling reaction; the Takahashi synthesis uses intramolecular alkylation of an allyl halide by a protected cyanohydrin anion; the Suginome synthesis utilizes a geranyl fragment; and the de Groot synthesis synthesizes humulene from a crude distillate of eucalyptus oil. Humulene can also by synthesized using a combination of four-component assembly and palladium-mediated cyclization, outlined below. This synthesis is noteworthy for the simplicity of the C−C bond constructions and cyclization steps, which it is believed will prove advantageous in the synthesis of related polyterpenoids.
s of humulene are produced in the brewing process. In a scientific study involving GC/MS analysis of samples and a trained sensory panel, it was found that the hyrdrolysis products of humulene epoxide II specifically produces a “hoppy” aroma in beer.
formation caused by histamine injections. Humulene also produced important inhibitory effects on tumor necrosis factor-α (TNFα) and interleukin-1 β (IL1B
) generation in carrageenan-injected rats.
Terpene
Terpenes are a large and diverse class of organic compounds, produced by a variety of plants, particularly conifers, though also by some insects such as termites or swallowtail butterflies, which emit terpenes from their osmeterium. They are often strong smelling and thus may have had a protective...
, which is a terpenoid
Terpenoid
The terpenoids , sometimes called isoprenoids, are a large and diverse class of naturally occurring organic chemicals similar to terpenes, derived from five-carbon isoprene units assembled and modified in thousands of ways. Most are multicyclic structures that differ from one another not only in...
consisting of 3 isoprene
Isoprene
Isoprene , or 2-methyl-1,3-butadiene, is a common organic compound with the formula CH2=CCH=CH2. Under standard conditions it is a colorless liquid...
units. It is found in the essential oil
Essential oil
An essential oil is a concentrated hydrophobic liquid containing volatile aroma compounds from plants. Essential oils are also known as volatile oils, ethereal oils or aetherolea, or simply as the "oil of" the plant from which they were extracted, such as oil of clove...
s of Humulus lupulus
Humulus lupulus
Humulus lupulus is a species of Humulus in the Cannabaceae family.Common hop is a dioecious, perennial herbaceous climbing plant which sends up new shoots in early spring and dies back to the cold-hardy rhizome in autumn...
(hops
Hop (plant)
Humulus, Hop, is a small genus of flowering plants native to temperate regions of the Northern Hemisphere. The female flowers of H. lupulus are known as hops, and are used as a culinary flavoring and stabilizer, especially in the brewing of beer...
) from which it derives its name. It is an isomer
Isomer
In chemistry, isomers are compounds with the same molecular formula but different structural formulas. Isomers do not necessarily share similar properties, unless they also have the same functional groups. There are many different classes of isomers, like stereoisomers, enantiomers, geometrical...
of β-caryophyllene
Caryophyllene
Caryophyllene , 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 , the essential oil of hemp Cannabis sativa, rosemary Rosmarinus oficinalis, and hops...
, and the two are often found together as a mixture in nature. It is also found in Lindera strychnifolia, and is one of the chemical compounds that contribute to the taste of the spice Vietnamese coriander
Vietnamese coriander
Persicaria odorata, the Vietnamese coriander, is an herb whose leaves are used in Southeast Asian cooking. Other English names for the herb include Vietnamese mint, Vietnamese cilantro, Cambodian mint and hot mint. The Vietnamese name is rau răm, while in Malaysia and Singapore it is called daun...
. It also contributes to the characteristic aroma of Cannabis sativa
Cannabis sativa
Cannabis sativa is an annual herbaceous plant in the Cannabaceae family. Humans have cultivated this herb throughout recorded history as a source of industrial fibre, seed oil, food, recreation, spiritual enlightenment and medicine...
, where it is present in the essential oil
Essential oil
An essential oil is a concentrated hydrophobic liquid containing volatile aroma compounds from plants. Essential oils are also known as volatile oils, ethereal oils or aetherolea, or simply as the "oil of" the plant from which they were extracted, such as oil of clove...
of the plant.
Synthesis
Humulene is one of many sesquiterpenoids that are derived from farnesyl diphosphate (FPP). The biosynthesis begins with the loss of diphosphate from FPP under the action of sesquiterpene synthesis enzymes, generating an allylic cation that is highly susceptible to intramolecular attacks.This biosynthesis can be mimicked in the lab by preparing allylic stanane from farnesol, termed Corey synthesis. There are diverse ways to synthesize humulene in the laboratory, involving differing closures of the C-C bond in the macrocycle. The McMurry synthesis uses a titanium-catalyzed carbonyl coupling reaction; the Takahashi synthesis uses intramolecular alkylation of an allyl halide by a protected cyanohydrin anion; the Suginome synthesis utilizes a geranyl fragment; and the de Groot synthesis synthesizes humulene from a crude distillate of eucalyptus oil. Humulene can also by synthesized using a combination of four-component assembly and palladium-mediated cyclization, outlined below. This synthesis is noteworthy for the simplicity of the C−C bond constructions and cyclization steps, which it is believed will prove advantageous in the synthesis of related polyterpenoids.
Occurrence
Humulene is one of the essential oils made in the flowering cone of the hops plant. The concentration of humulene varies among different varieties of the plant. Humulene and its reaction products in the brewing process of beer is gives many beers their “hoppy” aroma. Noble hop varieties have been found to have higher levels of humulene, while other bitter hop varieties contain low levels. Multiple epoxideEpoxide
An epoxide is a cyclic ether with three ring atoms. This ring approximately defines an equilateral triangle, which makes it highly strained. The strained ring makes epoxides more reactive than other ethers. Simple epoxides are named from the parent compound ethylene oxide or oxirane, such as in...
s of humulene are produced in the brewing process. In a scientific study involving GC/MS analysis of samples and a trained sensory panel, it was found that the hyrdrolysis products of humulene epoxide II specifically produces a “hoppy” aroma in beer.
Biological effects
Humulene has been found to produce anti-inflammatory effects, and has potential to be an effective treatment or management tool for inflammatory diseases. It produces similar effects to dexamethazone, and was found to decrease the edemaEdema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
formation caused by histamine injections. Humulene also produced important inhibitory effects on tumor necrosis factor-α (TNFα) and interleukin-1 β (IL1B
IL1B
Interleukin-1 beta also known as catabolin, is a cytokine protein that in humans is encoded by the IL1B gene. IL-1β precursor is cleaved by caspase 1 . Cytosolic thiol protease cleaves the product to form mature IL-1β.- Function :Interleukin 1 was discovered by Gery in 1972...
) generation in carrageenan-injected rats.