Lupulone

Last updated
Lupulone
Lupulone.svg
Lupulone chemical structure
Names
IUPAC name
3,5-Dihydroxy-2,6,6-tris(3-methylbuten-2-yl)-4-(3-methyl-1-oxobutyl)cyclohexa-2,4-dien-1-one [1]
Identifiers
3D model (JSmol)
6983327
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.006.734 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 207-405-3
KEGG
PubChem CID
RTECS number
  • OK5950000
UNII
  • InChI=1S/C26H38O4/c1-16(2)9-10-20-23(28)22(21(27)15-19(7)8)25(30)26(24(20)29,13-11-17(3)4)14-12-18(5)6/h9,11-12,19,28,30H,10,13-15H2,1-8H3
    Key: WPVSVIXDXMNGGN-UHFFFAOYSA-N [2]
  • O=C1C(/C\C=C(/C)C)=C(/O)\C(=C(\O)C1(C\C=C(/C)C)C\C=C(/C)C)C(=O)CC(C)C
Properties
C26H38O4
Molar mass 414.586 g·mol−1
Melting point 92–94 °C (198–201 °F; 365–367 K)
Boiling point 498 °C (928 °F; 771 K)
Insoluble
Acidity (pKa)4.20
Hazards
NFPA 704 (fire diamond)
NFPA 704.svgHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 2: Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur. Flash point between 38 and 93 °C (100 and 200 °F). E.g. diesel fuelInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
2
0
Flash point 269°C
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Lupulone is an organic chemical compound with the molecular formula C 26 H 38 O 4 and an appearance of a yellow powder which was historically used in beer brewing.

Contents

History

Since lupulone is found as a component of hops, the history of the compound can be traced back to 736 AD in southern Germany where hops plant were first cultivated. The commercial production of using lupulone in brewing was not until 1079 AD. The reason that lupulone was not utilized in beer brewing earlier on may be due to the fact that the hops plants has a bitter taste. However, brewers began to realize that beta acids of hops provided very little bitterness to the beer. Eventually, hops brewing with the use of lupulone made its way to the United States about 6 centuries later in 1629 after England introduced it. [3]

Synthesis

A synthesis pathway of lupulone involves the alkenylation of 2-acylcyclohexane-1, 3, 5-triones with bromides and liquid ammonia in ether as a base, which yields 4,6,6-trialkenyl derivatives (β-acids) [4]

Lupulones are hops β-acids, which are one the main ingredients of hops resin. Hops are important for beer brewing because they provides the unique bitter taste, smell and foam stability of beer. More importantly, lupulones are a natural alternative to antibiotics for bioethanol production. The problem with lupulone is that it oxidizes easily, resulting in the loss of its antimicrobial activity. Lupulones are very reactive with 1-hydroxyethyl radicals, as shown by the free energy change for an electron-transfer reaction. 1-hydroxyethyl is a major radical species formed during beer brewing. The major products of this reaction were hydroxylated lupulone derivatives and 1-hydroxylethyl radicals. These results suggest that the prenyl side chains of hops β-acids are the reaction centers. [5] [6]

Lupulone synthesis.png

Reactions

Lupolones are very reactive towards the 1-hydroxyethyl radical and are very oxidizable. Oxidation causes decomposition resulting in loss of the lupulone antimicrobial activity. The β-acid is less acidic and water solubule than the isomerized α-acids. The hop acids act as ionophores against Gram-positive bacteria, inhibiting their growth. This activity results from the hydrophobic interactions of prenyl groups present in a α- and β-acid structure with the bacterial cell walls. [5]

Applications

Derived from the cones of the female hop plant, lupulone is otherwise called a β-acid that contributes to the overall bitter flavor and aroma of beer along with α-acids. Both acids of the hops plant are added as the malted barley is boiled in water. This boiling process causes the bitter α-acids to go through thermal isomerization to form the extremely bitter taste of iso-α-acids. The β-acids, in this case lupulone, are oxidized during the boiling process to create products that also influence the taste and aroma of the beer but not as to a great extent as the α-acids. The bitterness of a brew greatly depends on the concentration of the α and β-acids, the amount of hops used and the length of time spent boiling. [7]

Lupulones have been used in products marketed for Varroa mite control in honeybees. The mechanism for control is not known, but lupulones may act as a repellent towards mites. Products with lupulines for beekeeping are considered non-toxic to humans and have low honeybee toxicity, but efficacy of those products for mite control are highly variable. [8]

Lupulones in in-vitro studies of colon carcinoma cells can induce apoptosis by interacting with receptors for cell death. In the context of cancer cell growth, lupulone can slow blood vessel formation in animal models. [9] In vitro studies have also shown lupulone to repress the growth of bacteria the cause skin infection such as Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus. [10]

Related Research Articles

<span class="mw-page-title-main">Hops</span> Flower used to flavour beer and other beverages

Hops are the flowers of the hop plant Humulus lupulus, a member of the Cannabaceae family of flowering plants. They are used primarily as a bittering, flavouring, and stability agent in beer, to which, in addition to bitterness, they impart floral, fruity, or citrus flavours and aromas. Hops are also used for various purposes in other beverages and herbal medicine. The hops plants have separate female and male plants, and only female plants are used for commercial production. The hop plant is a vigorous, climbing, herbaceous perennial, usually trained to grow up strings in a field called a hopfield, hop garden, or hop yard when grown commercially. Many different varieties of hops are grown by farmers around the world, with different types used for particular styles of beer.

<i>Humulus</i> Genus of flowering plants belonging to the hemp and hackberry family

Humulus, or hop, is a small genus of flowering plants in the family Cannabaceae. The hop is native to temperate regions of the Northern Hemisphere. Hops are the female flowers of the hop species H. lupulus; as a main flavor and aroma ingredient in many beer styles, H. lupulus is widely cultivated for use by the brewing industry.

<i>Varroa destructor</i> Species of mite

Varroa destructor, the Varroa mite, is an external parasitic mite that attacks and feeds on honey bees and is one of the most damaging honey bee pests in the world. A significant mite infestation leads to the death of a honey bee colony, usually in the late autumn through early spring. Without management for Varroa mite, honey bee colonies typically collapse within 2 to 3 years in temperate climates. These mites can infest Apis mellifera, the western honey bee, and Apis cerana, the Asian honey bee. Due to very similar physical characteristics, this species was thought to be the closely related Varroa jacobsoni prior to 2000, but they were found to be two separate species after DNA analysis.

<i>Humulus lupulus</i> Species of flowering plant

Humulus lupulus, the common hop or hops, is a species of flowering plant in the hemp family Cannabaceae, native to West Asia, Europe and North America. It is a perennial, herbaceous climbing plant which sends up new shoots in early spring and dies back to a cold-hardy rhizome in autumn. It is dioecious.

<span class="mw-page-title-main">Knorr pyrrole synthesis</span> Chemical reaction

The Knorr pyrrole synthesis is a widely used chemical reaction that synthesizes substituted pyrroles (3). The method involves the reaction of an α-amino-ketone (1) and a compound containing an electron-withdrawing group α to a carbonyl group (2).

<span class="mw-page-title-main">2-Iodoxybenzoic acid</span> Chemical compound

2-Iodoxybenzoic acid (IBX) is an organic compound used in organic synthesis as an oxidizing agent. This periodinane is especially suited to oxidize alcohols to aldehydes. IBX is prepared from 2-iodobenzoic acid, potassium bromate, and sulfuric acid. Frigerio and co-workers have also demonstrated, in 1999 that potassium bromate may be replaced by commercially available Oxone. One of the main drawbacks of IBX is its limited solubility; IBX is insoluble in many common organic solvents. In the past, it was believed that IBX was shock sensitive, but it was later proposed that samples of IBX were shock sensitive due to the residual potassium bromate left from its preparation. Commercial IBX is stabilized by carboxylic acids such as benzoic acid and isophthalic acid.

<span class="mw-page-title-main">Humulene</span> Chemical compound

Humulene, also known as α-humulene or α-caryophyllene, is a naturally occurring monocyclic sesquiterpene (C15H24), containing an 11-membered ring and consisting of 3 isoprene units containing three nonconjugated C=C double bonds, two of them being triply substituted and one being doubly substituted. It was first found in the essential oils of Humulus lupulus (hops), from which it derives its name. Humulene is an isomer of β-caryophyllene, and the two are often found together as a mixture in many aromatic plants.

Oxidative decarboxylation is a decarboxylation reaction caused by oxidation. Most are accompanied by α- Ketoglutarate α- Decarboxylation caused by dehydrogenation of hydroxyl carboxylic acids such as carbonyl carboxylic acid, malic acid, isocitric acid, etc.

A bitterant is a chemical that is added to a product to make it smell or taste bitter. Bitterants are commonly used as aversive agents to discourage the inhalation or ingestion of toxic substances.

<span class="mw-page-title-main">Manganese(III) acetate</span> Chemical compound

Manganese(III) acetate describes a family of materials with the approximate formula Mn(O2CCH3)3. These materials are brown solids that are soluble in acetic acid and water. They are used in organic synthesis as oxidizing agents.

<span class="mw-page-title-main">Alpha acid</span>

Alpha acids are a class of chemical compounds primarily of importance to the production of beer. They are found in the resin glands of the flowers of the hop plant and are the source of hop bitterness.

<span class="mw-page-title-main">Isohumulone</span> Chemical compound

Isohumulones are chemical compounds that contribute to the bitter taste of beer and are in the class of compounds known as iso-alpha acids. They are found in hops.

<span class="mw-page-title-main">Xanthohumol</span> Chemical compound

Xanthohumol is a natural product found in the female inflorescences of Humulus lupulus, also known as hops. This compound is also found in beer and belongs to a class of compounds that contribute to the bitterness and flavor of hops. Xanthohumol is a prenylated chalconoid, biosynthesized by a type III polyketide synthase (PKS) and subsequent modifying enzymes.

The α-ketol rearrangement is the acid-, base-, or heat-induced 1,2-migration of an alkyl or aryl group in an α-hydroxy ketone or aldehyde to give an isomeric product.

When drinking beer, there are many factors to be considered. Principal among them are bitterness, the variety of flavours present in the beverage and their intensity, alcohol content, and colour. Standards for those characteristics allow a more objective and uniform determination to be made on the overall qualities of any beer.

The Pinnick oxidation is an organic reaction by which aldehydes can be oxidized into their corresponding carboxylic acids using sodium chlorite (NaClO2) under mild acidic conditions. It was originally developed by Lindgren and Nilsson. The typical reaction conditions used today were developed by G. A. Kraus. H.W. Pinnick later demonstrated that these conditions could be applied to oxidize α,β-unsaturated aldehydes. There exist many different reactions to oxidize aldehydes, but only a few are amenable to a broad range of functional groups. The Pinnick oxidation has proven to be both tolerant of sensitive functionalities and capable of reacting with sterically hindered groups. This reaction is especially useful for oxidizing α,β-unsaturated aldehydes, and another one of its advantages is its relatively low cost.

<span class="mw-page-title-main">Humulone</span> Chemical compound

Humulone, a vinylogous type of organic acid, is a bitter-tasting chemical compound found in the resin of mature hops. Humulone is a prevalent member of the class of compounds known as alpha acids, which collectively give hopped beer its characteristic bitter flavor.

<span class="mw-page-title-main">Beer chemistry</span> Brewery science and beer chemical composition

The chemical compounds in beer give it a distinctive taste, smell and appearance. The majority of compounds in beer come from the metabolic activities of plants and yeast and so are covered by the fields of biochemistry and organic chemistry. The main exception is that beer contains over 90% water and the mineral ions in the water (hardness) can have a significant effect upon the taste.

<span class="mw-page-title-main">2,3,4-Pentanetrione</span> Chemical compound

2,3,4-Pentanetrione (or IUPAC name pentane-2,3,4-trione, triketopentane or dimethyl triketone) is the simplest linear triketone, a ketone with three C=O groups. It is an organic molecule with formula CH3COCOCOCH3.

A beerfault or defect is a flavour deterioration caused by chemical changes of organic compounds in beer, either due to improper production processes, or storage. Chemicals that can cause flavour defects in beer are aldehydes, lipids, and sulfur compounds. Small fluctuations within fermentation byproducts can lead to the concentration of one or more of these chemicals exceeding the standard threshold, creating a flavour defect.

References

  1. "Lupulone". pubchem.ncbi.nlm.nih.gov. Retrieved 16 May 2024.
  2. "Lupulone | C26H38O4 | ChemSpider".
  3. "The Basics of Hops". Archived from the original on 23 January 2013. Retrieved 16 May 2024.
  4. Collins, M.; Laws, D. R. J.; McGuinness, J. D.; Elvidge, J. A. (1971). "Chemistry of hop constituents. Part XXXVIII. Alkenylation of 2-acylcyclohexane-1,3,5-triones and further evidence concerning the fine structure of hop β-acids". J. Chem. Soc. C: 3814–3818. doi:10.1039/J39710003814.
  5. 1 2 de Almeida, Natália E. C.; do Nascimento, Eduardo S. P.; Cardoso, Daniel R. (24 October 2012). "On the Reaction of Lupulones, Hops β-Acids, with 1-Hydroxyethyl Radical". Journal of Agricultural and Food Chemistry. 60 (42): 10649–10656. doi:10.1021/jf302708c. PMID   23031058.
  6. Tyrrell, Elizabeth; Archer, Roland; Tucknott, Matt; Colston, Kay; Pirianov, Grisha; Ramanthan, Dharahana; Dhillon, Rajdeep; Sinclair, Alex; Skinner, G.A. (March 2012). "The synthesis and anticancer effects of a range of natural and unnatural hop β-acids on breast cancer cells". Phytochemistry Letters. 5 (1): 144–149. Bibcode:2012PChL....5..144T. doi:10.1016/j.phytol.2011.11.011.
  7. Pyle, N. Norm Pyle’s Hop FAQ. http://realbeer.com/hops/FAQ.html (accessed 1-3-07). 4 Harris, D.C. Quantitative Chemical Analysis ,6th Edition; W.H. Freeman and Co.: New York, 2003: pp 734-739.
  8. Jack, Cameron J; Ellis, James D (1 September 2021). "Integrated Pest Management Control of Varroa destructor (Acari: Varroidae), the Most Damaging Pest of (Apis mellifera L. (Hymenoptera: Apidae)) Colonies". Journal of Insect Science. 21 (5): 6. doi:10.1093/jisesa/ieab058. PMC   8449538 . PMID   34536080.
  9. Iniguez, Alejandro Bravo; Zhu, Mei-Jun (17 June 2021). "Hop bioactive compounds in prevention of nutrition-related noncommunicable diseases". Critical Reviews in Food Science and Nutrition. 61 (11): 1900–1913. doi:10.1080/10408398.2020.1767537.
  10. Chen, W.; Becker, T.; Qian, F.; Ring, J. (February 2014). "Beer and beer compounds: physiological effects on skin health". Journal of the European Academy of Dermatology and Venereology. 28 (2): 142–150. doi:10.1111/jdv.12204.