Xanthohumol

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]

Xanthohumol

Chemical structure of xanthohumol
Names
Preferred IUPAC name 2′,4,4′-Trihydroxy-6′-methoxy-3′-(3-methylbut-2-en-1-yl)chalcone
Identifiers
CAS Number	6754-58-1 N
3D model (JSmol)	Interactive image
ChEBI	CHEBI:66331 N
ChEMBL	ChEMBL253896 Y
ChemSpider	555077 Y
ECHA InfoCard	100.123.285
PubChem CID	639665
RTECS number	UD5574117
UNII	T4467YT1NT Y
CompTox Dashboard (EPA)	DTXSID00893171
InChI 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+ Y Key: ORXQGKIUCDPEAJ-YRNVUSSQSA-N Y
SMILES O=C(c1c(OC)cc(O)c(c1O)C/C=C(\C)C)\C=C\c2ccc(O)cc2
Properties
Chemical formula	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). N verify (what is YN ?) Infobox references

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.

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

• Isoxanthohumol, the corresponding prenylated flavanone
• 8-Prenylnaringenin, a related prenylflavanoid with estrogenic activity
• Alpha acids, a class of bitter compounds in hops
• Myrcene, humulene, and caryophyllene, essential oils in hops