Xanthohumol

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Xanthohumol
Chemical structure of xanthohumol Xanthohumol v2.svg
Chemical structure of xanthohumol
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).
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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] Xanthohumol may have potential as a killer of bladder cancer. [13]

See also

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.
  13. ↑ M.J. Bolt, J. Oceguera, A. Rivera Tostado, C.D. Candler, E. Mosa, K.Safari, M.G. Mancini, M.A. Mancini. A phenotypic screen identifies xanthohumol and other flavonoids as killers of bladder cancer. Pharmacological Research - Natural Products 2025 June vol 7, Pages 100236. [https://doi.org/10.1016/j.prenap.2025.100236.
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