Humulone (α-lupulic acid), a vinylogous 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 Hops are the flowers (also called seed cones or strobiles) 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 whi ...

('' Humulus lupulus''). Humulone is a prevalent member of the class of compounds known as alpha acids, which collectively give hopped beer its characteristic bitter flavor.

Chemistry

In terms of structure, humulone is a phloroglucinol

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. F ...

with three

isoprenoid The terpenoids, also known as isoprenoids, are a class of naturally occurring organic chemicals derived from the 5-carbon compound isoprene and its derivatives called terpenes, diterpenes, etc. While sometimes used interchangeably with "terpenes", ...

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 te ...

moieties that give rise to its designation as an acid lie in their vinylogous 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 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 Two-dimensional nuclear magnetic resonance spectroscopy (2D NMR) is a set of nuclear magnetic resonance spectroscopy (NMR) methods which give data plotted in a space defined by two frequency axes rather than one. Types of 2D NMR include correlation ...

2D NMR, the biosynthesis of humulone in ''Humulus lupulus'' starts with an

isovaleryl-CoA Isovaleryl-coenzyme A, also known as isovaleryl-CoA, is an intermediate in the metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main fun ...

unit and 3

malonyl-CoA Malonyl-CoA is a coenzyme A derivative of malonic acid. Functions It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis. Fatty acid biosynthesis Malonyl-CoA provides 2-carbon units to fatty acids and commi ...

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 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 an ...

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 of ...

effects.

References

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