Xanthohumol

Last updated
Xanthohumol
Xanthohumol.svg
Names
Preferred IUPAC name
2′,4,4′-Trihydroxy-6′-methoxy-3′-(3-methylbut-2-en-1-yl)chalcone
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.123.285 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
RTECS number
  • UD5574117
UNII
  • InChI=1S/C21H22O5/c1-13(2)4-10-16-18(24)12-19(26-3)20(21(16)25)17(23)11-7-14-5-8-15(22)9-6-14/h4-9,11-12,22,24-25H,10H2,1-3H3/b11-7+ Yes check.svgY
    Key: ORXQGKIUCDPEAJ-YRNVUSSQSA-N Yes check.svgY
  • O=C(c1c(OC)cc(O)c(c1O)C/C=C(\C)C)\C=C\c2ccc(O)cc2
Properties
C21H22O5
Molar mass 354.402 g·mol−1
Density 1.24 g/cm3 [1]
Melting point 157–159 °C (315–318 °F; 430–432 K) [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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. [2] Xanthohumol is a prenylated chalconoid, biosynthesized by a type III polyketide synthase (PKS) and subsequent modifying enzymes. [3] [4]

Contents

Biosynthesis

Xanthohumol is a prenylated chalconoid derived from a plant type III PKS, and is synthesized in the glandular trichromes of hop cones. [2] L-Phenylalanine serves as the starting material, which is converted to cinnamic acid by the PLP-dependent phenylalanine ammonia lyase. [5] [6] Cinnamic acid is oxidized by cinnamate-4-hydroxylase and loaded onto Coenzyme A (CoA) by 4-coumarate CoA ligase to yield 4-hydroxy-cinnamoyl CoA, the starter unit for PKS extension. [5] [6] This molecule is extended three times with malonyl CoA, cyclized through a Claisen condensation, and aromatized through tautomerization to form naringenin chalcone (chalconaringenin). [5] This intermediate has the potential to form a variety of different products depending on the enzymes that modify the core structure. [2] [5] In the case of xanthohumol, a prenyltransferase called Humulus lupulus prenyltransferase 1 (HlPT-1) attaches a molecule of dimethylallyl pyrophosphate from the DXP pathway. [7] HlPT-1 has a broad substrate specificity and also participates in making other prenylated flavonoids in the hop plant. [7] Finally, an O-methyltransferase methylates a phenol substituent using S-adenosyl methionine. [6] Total syntheses of xanthohumol and derivatives have been achieved, though extraction from hops remains a primary source. [8] [9]

The biosynthesis of Xanthohumol utilizes building blocks from plant secondary metabolism, and is catalyzed by a type III PKS and accessory modifying enzymes. Xanthohumol Biosynthesis v2.jpg
The biosynthesis of Xanthohumol utilizes building blocks from plant secondary metabolism, and is catalyzed by a type III PKS and accessory modifying enzymes.

Beer

In commercial beers, the concentration of xanthohumol ranges from about 2 μg/L – 1.2 mg/L. [10] During the brewing process, xanthohumol and other prenylated flavonoids are lost as they are converted to the corresponding flavanones. [11] Different hop varieties and different beers contain varying quantities of xanthohumol. [2]

Research

Xanthohumol is under basic research for its potential biological properties. [10] Xanthohumol can be extracted with pressurized hot water. [12]

See also

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.

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

Cinnamic acid is an organic compound with the formula C6H5-CH=CH-COOH. It is a white crystalline compound that is slightly soluble in water, and freely soluble in many organic solvents. Classified as an unsaturated carboxylic acid, it occurs naturally in a number of plants. It exists as both a cis and a trans isomer, although the latter is more common.

<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">Rutin</span> Chemical compound

Rutin is the glycoside combining the flavonol quercetin and the disaccharide rutinose. It is a flavonoid glycoside found in a wide variety of plants, including citrus.

<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.

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

Hesperidin is a flavanone glycoside found in citrus fruits. Its aglycone is hesperetin. Its name is derived from the word "hesperidium", for fruit produced by citrus trees.

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

Apigenin (4′,5,7-trihydroxyflavone), found in many plants, is a natural product belonging to the flavone class that is the aglycone of several naturally occurring glycosides. It is a yellow crystalline solid that has been used to dye wool.

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

The phenylpropanoids are a diverse family of organic compounds that are biosynthesized by plants from the amino acids phenylalanine and tyrosine in the shikimic acid pathway. Their name is derived from the six-carbon, aromatic phenyl group and the three-carbon propene tail of coumaric acid, which is the central intermediate in phenylpropanoid biosynthesis. From 4-coumaroyl-CoA emanates the biosynthesis of myriad natural products including lignols, flavonoids, isoflavonoids, coumarins, aurones, stilbenes, catechin, and phenylpropanoids. The coumaroyl component is produced from cinnamic acid.

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

Daidzein is a naturally occurring compound found exclusively in soybeans and other legumes and structurally belongs to a class of compounds known as isoflavones. Daidzein and other isoflavones are produced in plants through the phenylpropanoid pathway of secondary metabolism and are used as signal carriers, and defense responses to pathogenic attacks. In humans, recent research has shown the viability of using daidzein in medicine for menopausal relief, osteoporosis, blood cholesterol, and lowering the risk of some hormone-related cancers, and heart disease. Despite the known health benefits, the use of both puerarin and daidzein is limited by their poor bioavailability and low water solubility.

<span class="mw-page-title-main">Flavones</span> Class of flavonoid chemical compounds

Flavones are a class of flavonoids based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one).

<span class="mw-page-title-main">Flavonoid biosynthesis</span>

Flavonoids are synthesized by the phenylpropanoid metabolic pathway in which the amino acid phenylalanine is used to produce 4-coumaroyl-CoA. This can be combined with malonyl-CoA to yield the true backbone of flavonoids, a group of compounds called chalcones, which contain two phenyl rings. Conjugate ring-closure of chalcones results in the familiar form of flavonoids, the three-ringed structure of a flavone. The metabolic pathway continues through a series of enzymatic modifications to yield flavanones → dihydroflavonols → anthocyanins. Along this pathway, many products can be formed, including the flavonols, flavan-3-ols, proanthocyanidins (tannins) and a host of other various polyphenolics.

<span class="mw-page-title-main">Phenylalanine ammonia-lyase</span>

The enzyme phenylalanine ammonia lyase (EC 4.3.1.24) catalyzes the conversion of L-phenylalanine to ammonia and trans-cinnamic acid.:

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

Prenylated flavonoids or prenylflavonoids are a sub-class of flavonoids. They are widely distributed throughout the plant kingdom. Some are known to have phytoestrogenic or antioxidant properties. They are given in the list of adaptogens in herbalism. Chemically they have a prenyl group attached to their flavonoid backbone. It is usually assumed that the addition of hydrophobic prenyl groups facilitate attachment to cell membranes. Prenylation may increase the potential activity of its original flavonoid.

<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.

The biosynthesis of phenylpropanoids involves a number of enzymes.

Breast enlargement supplements are frequently portrayed as being a natural means to increase breast size, and with the suggestion that they are free from risk. The popularity of breast enlargement supplements stems from their heavy promotion toward women. Though there has been historical folklore about using herbs for breast enlargement, there is no scientific evidence to support the effectiveness of any breast enlargement supplement. At times, testimonials by companies have been faked.

<span class="mw-page-title-main">8-Prenylnaringenin</span> Chemical compound

8-Prenylnaringenin (8-PN; also known as flavaprenin, (S)-8-dimethylallylnaringenin, hopein, or sophoraflavanone B) is a prenylflavonoid phytoestrogen. It is reported to be the most estrogenic phytoestrogen known. The compound is equipotent at the two forms of estrogen receptors, ERα and ERβ, and it acts as a full agonist of ERα. Its effects are similar to those of estradiol, but it is considerably less potent in comparison.

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

Isoxanthohumol is a prenylflavonoid, and it is a phytoestrogen. It is abbreviated as IX or IXN.

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

Fumitremorgins are tremorogenic metabolites of Aspergillus and Penicillium, that belong to a class of naturally occurring 2,5-diketopiperazines.

References

  1. 1 2 Xanthohumol from hop (Humulus lupus), Santa Cruz Biotechnology
  2. 1 2 3 4 Stevens, Jan F.; Page, Jonathan E. (May 2004). "Xanthohumol and related prenylflavonoids from hops and beer: to your good health!". Phytochemistry. 65 (10): 1317–1330. Bibcode:2004PChem..65.1317S. doi:10.1016/j.phytochem.2004.04.025. ISSN   0031-9422. PMID   15231405.
  3. Goese, Markus; Kammhuber, Klaus; Bacher, Adelbert; Zenk, Meinhart H.; Eisenreich, Wolfgang (1999-07-15). "Biosynthesis of bitter acids in hops". European Journal of Biochemistry. 263 (2): 447–454. doi: 10.1046/j.1432-1327.1999.00518.x . ISSN   1432-1033. PMID   10406953.
  4. Wang, Guodong; Tian, Li; Aziz, Naveed; Broun, Pierre; Dai, Xinbin; He, Ji; King, Andrew; Zhao, Patrick X.; Dixon, Richard A. (November 2008). "Terpene biosynthesis in glandular trichomes of hop". Plant Physiology. 148 (3): 1254–1266. doi:10.1104/pp.108.125187. ISSN   0032-0889. PMC   2577278 . PMID   18775972.
  5. 1 2 3 4 M., Dewick, Paul (9 March 2009). Medicinal natural products : a biosynthetic approach. Wiley. ISBN   978-0-470-74168-9. OCLC   259265604.{{cite book}}: CS1 maint: multiple names: authors list (link)
  6. 1 2 3 Nagel, Jana; Culley, Lana K.; Lu, Yuping; Liu, Enwu; Matthews, Paul D.; Stevens, Jan F.; Page, Jonathan E. (January 2008). "EST analysis of hop glandular trichomes identifies an O-methyltransferase that catalyzes the biosynthesis of xanthohumol". The Plant Cell. 20 (1): 186–200. doi:10.1105/tpc.107.055178. ISSN   1040-4651. PMC   2254931 . PMID   18223037.
  7. 1 2 Tsurumaru, Yusuke; Sasaki, Kanako; Miyawaki, Tatsuya; Uto, Yoshihiro; Momma, Takayuki; Umemoto, Naoyuki; Momose, Masaki; Yazaki, Kazufumi (2012-01-06). "HlPT-1, a membrane-bound prenyltransferase responsible for the biosynthesis of bitter acids in hops". Biochemical and Biophysical Research Communications. 417 (1): 393–398. doi:10.1016/j.bbrc.2011.11.125. ISSN   1090-2104. PMID   22166201.
  8. Khupse, Rahul S.; Erhardt, Paul W. (2007-09-01). "Total Synthesis of Xanthohumol". Journal of Natural Products. 70 (9): 1507–1509. doi:10.1021/np070158y. ISSN   0163-3864. PMID   17844997.
  9. Zhang, Baoxin; Duan, Dongzhu; Ge, Chunpo; Yao, Juan; Liu, Yaping; Li, Xinming; Fang, Jianguo (2015-02-26). "Synthesis of Xanthohumol Analogues and Discovery of Potent Thioredoxin Reductase Inhibitor as Potential Anticancer Agent". Journal of Medicinal Chemistry. 58 (4): 1795–1805. doi:10.1021/jm5016507. ISSN   0022-2623. PMID   25629304.
  10. 1 2 Gerhäuser, Clarissa (September 2005). "Beer constituents as potential cancer chemopreventive agents". European Journal of Cancer. 41 (13): 1941–1954. doi:10.1016/j.ejca.2005.04.012. ISSN   0959-8049. PMID   15953717.
  11. Stevens, Jan F.; Taylor, Alan W.; Clawson, Jeff E.; Deinzer, Max L. (1999-06-01). "Fate of Xanthohumol and Related Prenylflavonoids from Hops to Beer". Journal of Agricultural and Food Chemistry. 47 (6): 2421–2428. doi:10.1021/jf990101k. ISSN   0021-8561. PMID   10794646.
  12. A. Gil-Ramírez, J.A. Mendiola, E. Arranz, A. Ruíz-Rodríguez, G. Reglero, E. Ibáñez, F.R. Marín. Highly isoxanthohumol enriched hop extract obtained by pressurized hot water extraction (PHWE). Chemical and functional characterization. Innovative Food Science and Emerging Technologies 2012 October, vol 16 Pages 54-60. doi: 10.1016/j.ifset.2012.04.006.