Xanthohumol

Xanthohumol is a prenylated chalconoid derived from a plant type III PKS, and is synthesized in the glandular trichromes of hop cones. L-Phenylalanine serves as the starting material, which is converted to cinnamic acid by the PLP-dependent phenylalanine ammonia lyase.{{Cite book|title=Medicinal natural products : a biosynthetic approach|last=M.|first=Dewick, Paul|date=9 March 2009 |publisher=Wiley |isbn=978-0-470-74168-9|oclc=259265604}}{{Cite journal|last1=Nagel|first1=Jana|last2=Culley|first2=Lana K.|last3=Lu|first3=Yuping|last4=Liu|first4=Enwu|last5=Matthews|first5=Paul D.|last6=Stevens|first6=Jan F.|last7=Page|first7=Jonathan E.|date=January 2008|title=EST analysis of hop glandular trichomes identifies an O-methyltransferase that catalyzes the biosynthesis of xanthohumol|journal=The Plant Cell|volume=20|issue=1|pages=186–200|doi=10.1105/tpc.107.055178|issn=1040-4651|pmc=2254931|pmid=18223037}} 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. This molecule is extended three times with malonyl CoA, cyclized through a Claisen condensation, and aromatized through tautomerization to form naringenin chalcone (chalconaringenin). This intermediate has the potential to form a variety of different products depending on the enzymes that modify the core structure. In the case of xanthohumol, a prenyltransferase called Humulus lupulus prenyltransferase 1 (HlPT-1) attaches a molecule of dimethylallyl pyrophosphate from the DXP pathway.{{Cite journal|last1=Tsurumaru|first1=Yusuke|last2=Sasaki|first2=Kanako|last3=Miyawaki|first3=Tatsuya|last4=Uto|first4=Yoshihiro|last5=Momma|first5=Takayuki|last6=Umemoto|first6=Naoyuki|last7=Momose|first7=Masaki|last8=Yazaki|first8=Kazufumi|date=2012-01-06|title=HlPT-1, a membrane-bound prenyltransferase responsible for the biosynthesis of bitter acids in hops|journal=Biochemical and Biophysical Research Communications|volume=417|issue=1|pages=393–398|doi=10.1016/j.bbrc.2011.11.125|issn=1090-2104|pmid=22166201}} HlPT-1 has a broad substrate specificity and also participates in making other prenylated flavonoids in the hop plant. Finally, an O-methyltransferase methylates a phenol substituent using S-adenosyl methionine. Total syntheses of xanthohumol and derivatives have been achieved, though extraction from hops remains a primary source.{{Cite journal|last1=Khupse|first1=Rahul S.|last2=Erhardt|first2=Paul W.|date=2007-09-01|title=Total Synthesis of Xanthohumol|journal=Journal of Natural Products|volume=70|issue=9|pages=1507–1509|doi=10.1021/np070158y|pmid=17844997|issn=0163-3864|url=https://figshare.com/articles/Total_Synthesis_of_Xanthohumol/2983579}}{{Cite journal|last1=Zhang|first1=Baoxin|last2=Duan|first2=Dongzhu|last3=Ge|first3=Chunpo|last4=Yao|first4=Juan|last5=Liu|first5=Yaping|last6=Li|first6=Xinming|last7=Fang|first7=Jianguo|date=2015-02-26|title=Synthesis of Xanthohumol Analogues and Discovery of Potent Thioredoxin Reductase Inhibitor as Potential Anticancer Agent|journal=Journal of Medicinal Chemistry|volume=58|issue=4|pages=1795–1805|doi=10.1021/jm5016507|pmid=25629304|issn=0022-2623}}

File:Xanthohumol Biosynthesis v2.jpg

In commercial beers, the concentration of xanthohumol ranges from about 2 μg/L – 1.2 mg/L.{{Cite journal|last=Gerhäuser|first=Clarissa|date=September 2005|title=Beer constituents as potential cancer chemopreventive agents|journal=European Journal of Cancer|volume=41|issue=13|pages=1941–1954|doi=10.1016/j.ejca.2005.04.012|issn=0959-8049|pmid=15953717}} During the brewing process, xanthohumol and other prenylated flavonoids are lost as they are converted to the corresponding flavanones.{{Cite journal|last1=Stevens|first1=Jan F.|last2=Taylor|first2=Alan W.|last3=Clawson|first3=Jeff E.|last4=Deinzer|first4=Max L.|date=1999-06-01|title=Fate of Xanthohumol and Related Prenylflavonoids from Hops to Beer|journal=Journal of Agricultural and Food Chemistry|volume=47|issue=6|pages=2421–2428|doi=10.1021/jf990101k|pmid=10794646|issn=0021-8561}} Different hop varieties and different beers contain varying quantities of xanthohumol.

Xanthohumol is under basic research for its potential biological properties. Xanthohumol can be extracted with pressurized hot water.A. Gil-Ramírez, J.A. Mendiola, E. Arranz, A. Ruíz-Rodríguez, G. Reglero, E. Ibáñez, F.R. Marín. [https://doi.org/10.1016/j.ifset.2012.04.006 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. [https://www.sciencedirect.com/science/article/pii/S1466856412000549 doi: 10.1016/j.ifset.2012.04.006].

• 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

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Category:Chalconoids

Category:O-methylated natural phenols

Category:Humulus