# Lupulone
**Lupulone** (CAS 468-28-0) is a beta-bitter acid (β-acid) from hops, *Humulus lupulus*, in which the acyl group is 3-methylbutanoyl; it is one of the triprenylated acylphloroglucinol compounds that make up the soft resins of the hop cone[1](https://pubchem.ncbi.nlm.nih.gov/compound/Lupulone) • [2](https://www.sciencedirect.com/topics/chemistry/lupulone). PubChem lists the molecular formula C26H38O4 and molecular weight 414.6 g/mol, with the IUPAC name 3,5-dihydroxy-2-(3-methylbutanoyl)-4,6,6-tris(3-methylbut-2-enyl)cyclohexa-2,4-dien-1-one[1](https://pubchem.ncbi.nlm.nih.gov/compound/Lupulone). It is recorded as an antimicrobial agent, antineoplastic agent, angiogenesis inhibitor, and apoptosis inducer[1](https://pubchem.ncbi.nlm.nih.gov/compound/Lupulone).
| Key fact | Detail |
|---|---|
| Class | β-acid (beta bitter acid) of hop resin; acyl group 3-methylbutanoyl[1](https://pubchem.ncbi.nlm.nih.gov/compound/Lupulone) |
| Formula / mass | C26H38O4, 414.6 g/mol[1](https://pubchem.ncbi.nlm.nih.gov/compound/Lupulone) |
| Congeners | colupulone, adlupulone, prelupulone, postlupulone; lupulone is 30–55% of total β-acids[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC6412513/) |
| Solubility | 8.5 mg/L in water at 100 °C and pH 5.6, versus about 250 mg/L for α-acids under the same conditions[4](https://kvasnyprumysl.cz/pdfs/kpr/2014/04/03.pdf) |
| Brewing behavior | Cannot isomerize during wort boiling; only trace amounts reach beer[2](https://www.sciencedirect.com/topics/chemistry/lupulone) • [5](https://onlinelibrary.wiley.com/doi/full/10.1002/jib.160) |
| Antibacterial potency | MIC 0.6–1.2 µg/mL against MRSA strains; generally more potent than the α-acid humulone[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC6472001/) • [7](https://www.mdpi.com/2076-3417/15/14/7806) |
| History | First isolated from hops by Lermer in 1863; structure proposed by Wöllmer in 1925 and corrected by Verzele and Govaert in 1949[4](https://kvasnyprumysl.cz/pdfs/kpr/2014/04/03.pdf) • [5](https://onlinelibrary.wiley.com/doi/full/10.1002/jib.160) |
## Structure and chemical properties
Lupulone belongs to the β-acid group of hop resins, which comprises five homologues: colupulone, lupulone, adlupulone, and minor quantities of prelupulone and postlupulone. The homologues differ in their acyl side chain, and the same nomenclature used for the α-acids accounts for these variations[2](https://www.sciencedirect.com/topics/chemistry/lupulone) • [5](https://onlinelibrary.wiley.com/doi/full/10.1002/jib.160). Structurally, the β-acids are the triprenylated analogs of the α-acids, carrying one more isoprenyl (prenyl) side chain[2](https://www.sciencedirect.com/topics/chemistry/lupulone).
That extra prenyl chain drives the physical behavior that distinguishes β-acids in brewing. The molecule as a whole is more hydrophobic than the α-acids, so β-acids are far less soluble in water: 8.5 mg/L at 100 °C and pH 5.6, against roughly 250 mg/L for α-acids under the same conditions[4](https://kvasnyprumysl.cz/pdfs/kpr/2014/04/03.pdf). The β-acids are weak acids with a pKa of approximately 6.1, and they are colorless crystals with melting points in the range 82–97 °C[2](https://www.sciencedirect.com/topics/chemistry/lupulone) • [4](https://kvasnyprumysl.cz/pdfs/kpr/2014/04/03.pdf).
## Occurrence in hops
Lupulone is produced in the lupulin glands of female hop cones[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC7136647/). All hops contain both α- and β-acids; commercial hop varieties can contain up to 10 wt% β-acids, and within the β-acid fraction lupulone accounts for 30–55% of the total[2](https://www.sciencedirect.com/topics/chemistry/lupulone) • [3](https://pmc.ncbi.nlm.nih.gov/articles/PMC6412513/). Isolating the α-acids from a hop extract leaves a rest product enriched in β-acids, the so-called beta or base extract[2](https://www.sciencedirect.com/topics/chemistry/lupulone). The ratio of α- to β-acids varies by variety: it can be below 1.0 for some aroma hops, while bitter hops range from 1.5 to 4.0[2](https://www.sciencedirect.com/topics/chemistry/lupulone).
Biosynthetically, β-acids such as lupulone are not modified after prenylation is complete, whereas the α-acid branch of the pathway requires an additional oxidation step to yield humulone and its congeners[2](https://www.sciencedirect.com/topics/chemistry/lupulone). Feeding studies with 14C-labeled acetic acid led to isolation of labeled humulone, lupulone, and colupulone, indicating an acetate precursor for the bitter acids[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC5566628/).
## Behavior in brewing
The defining brewing property of the β-acids is their instability in the presence of oxygen and their tendency to oxidize to more soluble products during hop processing, storage, and, to a small extent, beer production[4](https://kvasnyprumysl.cz/pdfs/kpr/2014/04/03.pdf). Unlike the α-acids, β-acids cannot isomerize during wort boiling because they lack the tertiary alcohol function on carbon atom 6, so substances such as "iso-beta acids" do not exist[2](https://www.sciencedirect.com/topics/chemistry/lupulone) • [4](https://kvasnyprumysl.cz/pdfs/kpr/2014/04/03.pdf). Because wort properties do not favor β-acid solubility, only trace amounts are transferred into beer[5](https://onlinelibrary.wiley.com/doi/full/10.1002/jib.160).
The best-known oxidation products are the hulupones, formed during long-term storage of hops; beers hopped with pre-oxidized β-acids show strong sensory bitterness, with the bittering yield of β-acid oxidation products reaching approximately 35–40% of the bitterness intensity of iso-α-acids[4](https://kvasnyprumysl.cz/pdfs/kpr/2014/04/03.pdf). In aged hops, these oxidation products largely compensate during wort boiling for the bitterness lost through the decline of α-acids[4](https://kvasnyprumysl.cz/pdfs/kpr/2014/04/03.pdf).
## Antimicrobial activity
Lupulone is a principal antibacterial constituent of hop extracts. Activity-guided fractionation and metabolome analysis identified colupulone and lupulone as the main contributors to the antibacterial activity of hop extracts[10](https://www.sciencedirect.com/science/article/pii/S0963996923003770). Against clinical MRSA and methicillin-sensitive *Staphylococcus aureus* isolates, lupulone was the most promising compound tested, with MICs of 0.6 to 1.2 µg/mL toward MRSA strains[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC6472001/). A 2025 systematic review and meta-analysis integrating data across 450 studies and 55 microbial strains found that lupulone showed significantly higher antimicrobial activity against non-food spoilage bacteria (MIC 4.20 µg/mL) than against food spoilage bacteria (12.40 µg/mL), and generally higher potency than the α-acid humulone[7](https://www.mdpi.com/2076-3417/15/14/7806).
The proposed mechanism of action is mainly related to the interference of the prenyl group, typical of hop acid chains, with cell plasma membrane function[2](https://www.sciencedirect.com/topics/chemistry/lupulone). Teuber and Schmalreck hypothesized that the antibacterial activity of lupulone and humulone against *Bacillus subtilis* is due to induced bacterial membrane leakage[11](https://akjournals.com/downloadpdf/journals/1886/12/1/article-p22.pdf).
**Synergy with antibiotics.** Hop constituents show positive co-action with conventional antibiotics. An antibacterial cream containing lupulone, neomycin, and polymyxin B sulfate showed co-action against the [Gram-positive bacteria](https://www.edgepedia.org/gram-positive-bacteria) tested, and some positive co-action against certain [Gram-negative bacteria](https://www.edgepedia.org/gram-negative-bacteria), though none against *E. coli*[12](https://www.sciencedirect.com/science/article/abs/pii/S0944711307002577). Reviews of humulone, lupulone, and xanthohumol report additive or synergistic effects with antibiotics including penicillin, erythromycin, tetracycline, vancomycin, linezolid, ciprofloxacin, and polymyxin B against Gram-positive bacteria[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC9036650/).
## Other biological effects and applications
PubChem records roles for lupulone as an antineoplastic agent, angiogenesis inhibitor, and apoptosis inducer, in addition to its antimicrobial role[1](https://pubchem.ncbi.nlm.nih.gov/compound/Lupulone). Reviews of [hop bitter acids](https://www.edgepedia.org/hop-bitter-acids) note potential sources for treatment or prevention of diseases including cancer, diabetes, osteoporosis, cardiovascular disease, and inflammatory and metabolic disorders[4](https://kvasnyprumysl.cz/pdfs/kpr/2014/04/03.pdf).
In animal nutrition, β-acids have found practical use as phytogenic feed additives, with applications reported in sugar production, distilling, and livestock sectors[4](https://kvasnyprumysl.cz/pdfs/kpr/2014/04/03.pdf). In poultry studies, microencapsulated β-acids at 30 mg/kg feed achieved a feed conversion ratio comparable to zinc [bacitracin](https://www.edgepedia.org/bacitracin), and lupulone reduced intestinal *Clostridium perfringens* counts by more than 4 log units, from log10 6.20 to 2.00 CFU/g; doses of 240 mg/kg or more induced adverse effects[14](https://pubmed.ncbi.nlm.nih.gov/42280732/). In a study of five hop compounds as candidates for poultry feed additives, lupulone showed a selective index of 15 ± 0.77 for antibacterial activity against *Bacillus subtilis* relative to cytotoxicity in chicken fibroblast cells[15](https://pubmed.ncbi.nlm.nih.gov/41121659/).
## References
1. [Lupulone, CID 68051, PubChem](https://pubchem.ncbi.nlm.nih.gov/compound/Lupulone)
2. [Lupulone – an overview, ScienceDirect Topics](https://www.sciencedirect.com/topics/chemistry/lupulone)
3. [Hop Compounds: Extraction Techniques, Chemical Analyses, Antioxidative, Antimicrobial, and Anticarcinogenic Effects, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC6412513/)
4. [Krofta, K. and Mikyška, A. (2014). Hop beta acids: Properties, significance and utilization. Kvasny Prumysl 60(4), 96–105](https://kvasnyprumysl.cz/pdfs/kpr/2014/04/03.pdf)
5. [Almaguer, C. et al. (2014). Humulus lupulus – a story that begs to be told. A review. Journal of the Institute of Brewing 120(4), 289–314](https://onlinelibrary.wiley.com/doi/full/10.1002/jib.160)
6. [Phenolic Compounds from Humulus lupulus as Natural Antimicrobial Products, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC6472001/)
7. [Antimicrobial Activity of Chemical Hop (Humulus lupulus) Compounds: A Systematic Review and Meta-Analysis, Applied Sciences](https://www.mdpi.com/2076-3417/15/14/7806)
8. [Expedient Synthesis of Lupulones and Their Derivatization to 2,8-7H-Dihydrochromen-7-ones, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7136647/)
9. [Hops (Humulus lupulus L.) Bitter Acids: Modulation of Rumen Fermentation, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC5566628/)
10. [Identification of colupulone and lupulone as the main contributors to the antibacterial activity of hop extracts, Food Research International](https://www.sciencedirect.com/science/article/pii/S0963996923003770)
11. [Antibacterial effects of biologically active ingredients in hop, European Journal of Microbiology and Immunology](https://akjournals.com/downloadpdf/journals/1886/12/1/article-p22.pdf)
12. [Positive antibacterial co-action between hop (Humulus lupulus) constituents and selected antibiotics, Phytomedicine](https://www.sciencedirect.com/science/article/abs/pii/S0944711307002577)
13. [Antibacterial effects of biologically active ingredients in hop, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC9036650/)
14. [Humulus lupulus L. in Animal Nutrition: A Comprehensive Review, PubMed](https://pubmed.ncbi.nlm.nih.gov/42280732/)
15. [Selective Antimicrobial and Cytotoxic Effects of Hop Compounds to Combat Poultry Antimicrobial Resistance, PubMed](https://pubmed.ncbi.nlm.nih.gov/41121659/)
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*Topic: Encyclopedia › Life and health › Biological foundations › Biochemistry and metabolism › Metabolism and metabolic pathways › Secondary and natural-product metabolism › Terpenoid and terpenophenolic metabolism › Terpenophenolic pathways › Hop bitter acid and Humulus pathways*
*Initially written Sep 17, 2026 · Reviewed: Sep 30, 2026; Oct 21, 2026 · Edited: Sep 30, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license