Humulone (α-lupulic acid), a

vinylogous In organic chemistry, vinylogy is the transmission of electronic effects through a conjugated organic bonding system. The concept was introduced in 1926 by Ludwig Claisen to explain the acidic properties of formylacetone and related ketoaldehydes ...

type of organic acid, is a

bitter Bitter may refer to: Common uses * Resentment, negative emotion or attitude, similar to being jaded, cynical or otherwise negatively affected by experience * Bitter (taste), one of the five basic tastes Books * '' Bitter (novel)'', a 2022 nove ...

-tasting

chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...

found in the resin of mature hops (''

Humulus lupulus ''Humulus lupulus'', the common hop or hops, is a species of flowering plant in the hemp family Cannabinaceae, native to Europe, western Asia and North America. It is a perennial, herbaceous climbing plant which sends up new shoots in early s ...

''). Humulone is a prevalent member of the class of compounds known as

alpha acid Alpha acids (α 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. Alpha acids may be isomerize ...

s, which collectively give hopped beer its characteristic bitter flavor.

Chemistry

In terms of structure, humulone is a

phloroglucinol Phloroglucinol is an organic compound with the formula C6H3(OH)3. It is a colorless solid. It is used in the synthesis of pharmaceuticals and explosives. Phloroglucinol is one of three isomeric benzenetriols. The other two isomers are hydroxyqu ...

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

with three isoprenoid side-chains. Two side-chains are prenyl groups and one is an isovaleryl group. The acidity of the ring

enol In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). The t ...

moieties that give rise to its designation as an acid lie in their

relationship with the ring and side chain carbonyl functional groups.

Isohumulone

During the brewing process, humulone degrades to ''cis-'' and ''trans-''

isohumulone 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. Beer The bitterness of beer is measured according to the International Bittern ...

. These “alpha acids” survive the boiling process, although numerous oxidized derivatives are produced. The iso-alpha acids are significantly more soluble than humulone at the pH levels typically present in the brewing process. : S-Humulone Isomerization

Laboratory synthesis

Humulone can be synthesized by the

acylation In chemistry, acylation (or alkanoylation) is the chemical reaction in which an acyl group () is added to a compound. The compound providing the acyl group is called the acylating agent. Because they form a strong electrophile when treated with ...

of benzene-1,2,3,5-tetrol with isovaleryl chloride to give 2,3,4,6-tetrahydroxyisovalerophenone. This step is followed by prenylation with 1-bromo-3-methyl-2-butene to give humulone. : Humulone synthesis

Biosynthesis

As determined by INADEQUATE 2D NMR, the biosynthesis of humulone in ''Humulus lupulus'' starts with an isovaleryl-CoA unit and 3 malonyl-CoA units catalyzed by phlorovalerophenone synthase. This conversion yields the benzenoid 3-methyl-1-(2,4,6-trihydroxyphenyl)butan-1-one.

Dimethylallyl pyrophosphate Dimethylallyl pyrophosphate (DMAPP; or alternatively, dimethylallyl diphosphate (DMADP); also isoprenyl pyrophosphate) is an isoprenoid precursor. It is a product of both the mevalonate pathway and the MEP pathway of isoprenoid precursor biosynt ...

is then obtained from the deoxyxylulose pathway, where prenylation of the benzenoid occurs, yielding humulone. :isovaleryl-CoA + 3 malonyl-CoA → 4 CoASH + 3 CO2 + 3-methyl-1-(2,4,6-trihydroxyphenyl)butan-1-one :3-methyl-1-(2,4,6-trihydroxyphenyl)butan-1-one + 2 DMAPP →C₂₁H₃₀O₅

Research

Humulone is under

basic research Basic research, also called pure research or fundamental research, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenomena. In contrast, applied rese ...

with

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...

studies to determine if it has biological properties, such as possible GABA_A receptor activity or

antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...

effects.

References

{{Reflist Cyclohexadienes 3-Hydroxypropenals Terpeno-phenolic compounds Bitter compounds Triols Secondary alcohols Tertiary alcohols Humulus