# Lactone
A lactone is a cyclic ester, formally defined by IUPAC as a cyclic ester of a hydroxy carboxylic acid containing a 1-oxacycloalkan-2-one structure, or an analog in which unsaturation or heteroatoms replace one or more ring carbon atoms[1](https://goldbook.iupac.org/terms/view/L03439). The functional group is the ring unit −C(=O)−O−, formed when a hydroxyl group and a carboxylic acid group in the same molecule condense with loss of water, a reaction called lactonization[1](https://goldbook.iupac.org/terms/view/L03439) • [2](https://organicchemistrydata.org/reusch/virtualtext/lactone-formation/). Lactones range from strained four-membered β-lactones through five- and six-membered γ- and δ-lactones to large macrocyclic systems[3](https://pubs.rsc.org/en/content/articlehtml/2026/py/d6py00239k), and they occur widely in nature as flavor and fragrance compounds, pharmacophores in macrolide antibiotics and sesquiterpene lactones, and signaling molecules in insects, vertebrates, and bacteria[3](https://pubs.rsc.org/en/content/articlehtml/2026/py/d6py00239k).
| Key fact | Detail |
|---|---|
| Definition | Cyclic esters of hydroxy carboxylic acids with a 1-oxacycloalkan-2-one structure, or analogs with unsaturation or heteroatoms in the ring[1](https://goldbook.iupac.org/terms/view/L03439) |
| Ring sizes | From four-membered β-lactones to five- and six-membered γ- and δ-lactones and macrocyclic systems; the largest known natural macrolide lactone has a 66-membered ring[3](https://pubs.rsc.org/en/content/articlehtml/2026/py/d6py00239k) • [4](https://pubs.rsc.org/en/content/articlehtml/2022/np/d2np00025c) |
| Formation thermodynamics | Lactonization of 4-hydroxybutanoic acid: ΔH° = +1.08 kcal/mole, ΔS° = +13.9 cal/°K mole, ΔG° = −3.1 kcal/mole, K_eq = 190[2](https://organicchemistrydata.org/reusch/virtualtext/lactone-formation/) |
| Ring-size effect | Four-membered β-lactone formation is strongly endergonic (ΔG° = +17 to +19 kcal/mole) because of ring strain[2](https://organicchemistrydata.org/reusch/virtualtext/lactone-formation/) |
| Industrial monomers | Lactide and ε-caprolactone are the most common ring-opening polymerization monomers, giving PLA and PCL[5](https://pubs.acs.org/ascecg/article/9/32/10664/449887/From-Lab-to-Market-Current-Strategies-for-the) |
| Biological role | 40 of 436 structures in a recent arthropod pheromone overview are lactones; γ-decalactone is the main contributor to peach aroma[6](https://pubs.rsc.org/en/content/articlehtml/2015/np/c5np00006h) • [7](https://pubmed.ncbi.nlm.nih.gov/32001520/) |
## Nomenclature and ring sizes
Traditional lactone names use Greek letters to indicate the position of the hydroxyl-bearing carbon in the parent hydroxy acid relative to the carboxyl group: an α-hydroxy acid would give an α-lactone, a β-hydroxy acid a four-membered β-lactone, a γ-hydroxy acid a five-membered γ-lactone, and a δ-hydroxy acid a six-membered δ-lactone[8](https://www.chem.ualberta.ca/~vederas/Chem_263/outlines/pdf/Chem263_Nov26_2013%20notes.pdf) • [9](https://pages.pomona.edu/~djo04747/110/Lecture_13_2020.pdf). The CAS index guide records that these Greek letters are used in the chemical literature to indicate the size of lactone rings[10](https://www.cas.org/sites/default/files/documents/indexguideapp.pdf).
Preferred IUPAC names instead treat lactones as heterocyclic pseudoketones. γ-Butyrolactone, for example, carries the preferred name oxolan-2-one, and δ-valerolactone is oxan-2-one[11](https://media.iupac.org/reports/provisional/abstract04/BB-prs310305/Chapter6-Sec65.pdf) • [12](https://pubchem.ncbi.nlm.nih.gov/compound/oxolan-2-one). By these rules, a lactone's position in the class-seniority order falls below that of acids and esters, yet above alcohols, amines, and imines[11](https://media.iupac.org/reports/provisional/abstract04/BB-prs310305/Chapter6-Sec65.pdf). For macrolides, an older IUPAC rule added "-olide" to the hydrocarbon name matching the carbon count of the lactone core acid, giving names such as nonanolide and decanolide; current rules name ten-membered lactones as derivatives of oxecin-2-one[13](https://pubs.rsc.org/en/content/articlehtml/2024/np/d3np00013c).
## Formation and thermodynamics
Lactonization is the intramolecular analog of ordinary Fischer esterification, in which the hydroxyl group attacks the protonated carboxyl carbon and water is expelled[2](https://organicchemistrydata.org/reusch/virtualtext/lactone-formation/) • [14](https://www.chem.uci.edu/files/smith_textbook/smi96656_c22_001_036.pdf). The thermodynamics differ sharply from intermolecular esterification. [Ethyl acetate](https://www.edgepedia.org/ethyl-acetate) formation from acetic acid and ethanol is modestly exothermic (ΔH° = −0.89 kcal/mole, ΔG° = −1.28 kcal/mole)[2](https://organicchemistrydata.org/reusch/virtualtext/lactone-formation/). Lactonization of 4-hydroxybutanoic acid to the five-membered γ-lactone is mildly endothermic, ΔH° = +1.08 kcal/mole, reflecting ring strain, because esters prefer a Z-conformation of the ester function that six-membered and smaller rings cannot adopt[2](https://organicchemistrydata.org/reusch/virtualtext/lactone-formation/). The large positive entropy of cyclization, ΔS° = +13.9 cal/°K mole, more than compensates, giving ΔG° = −3.1 kcal/mole and K_eq = 190, so the hydroxy acid lactonizes spontaneously and completely once formed[2](https://organicchemistrydata.org/reusch/virtualtext/lactone-formation/).
**Ring size governs the outcome.** The six-membered δ-lactone from 5-hydroxypentanoic acid is slightly more strained but still forms exergonically, and efforts to prepare the free hydroxy acid have failed[2](https://organicchemistrydata.org/reusch/virtualtext/lactone-formation/). By contrast, cyclization of 3-hydroxypropanoic acid to the four-membered β-lactone has ΔH° of +23 to 25 kcal/mole and ΔG° of +17 to +19 kcal/mole, so it does not proceed spontaneously and the hydroxy acid tends to dimerize instead[2](https://organicchemistrydata.org/reusch/virtualtext/lactone-formation/). Terminal hydroxy acids with chains longer than six carbons may either lactonize or polymerize; at high hydroxy acid concentration dimerization and polymerization are favored, while at low concentrations lactonization becomes competitive[2](https://organicchemistrydata.org/reusch/virtualtext/lactone-formation/).
In nature, hydroxy acids or their activated forms are usually the precursors, and in polyketide-derived lactones such as macrolide antibiotics the lactone ring may be formed directly by the final thioesterase releasing the growing chain from the polyketide synthase without a free hydroxy acid intermediate[6](https://pubs.rsc.org/en/content/articlehtml/2015/np/c5np00006h). In dairy chemistry, the long-accepted two-step mechanism for lactone formation in [Gouda cheese](https://www.edgepedia.org/gouda-cheese), hydrolysis of esterified hydroxy fatty acids followed by spontaneous lactonization, was questioned by Alewijn and colleagues, who proposed instead a one-step intramolecular trans-esterification on the triglyceride forming δ-lactones and long-chain γ-lactones[15](https://repository.lib.ncsu.edu/bitstreams/3fb171ec-b028-4ecf-bc2b-4953e0a9b3d2/download).
## Hydrolysis and reactivity
Lactones hydrolyze to their parent hydroxy carboxylic acids, and the reaction is an equilibrium in water whose position depends on pH[16](https://inchem.org/documents/jecfa/jecmono/v52je13.htm). Under acidic conditions, five- and six-membered lactones usually reach an equilibrium point because the reverse lactonization competes[17](https://catalogimages.wiley.com/images/db/pdf/9781118832936.excerpt.pdf); removal of water shifts the equilibrium back toward ring closure[18](https://www.chemistrysteps.com/hydrolysis-of-lactones/). When the hydrolysis is carried out under base, the product is a carboxylate salt instead of the corresponding acid; since this anion is a weak electrophile and resists closing back into the ring, the equilibrium is pushed far toward the open-chain product.[18](https://www.chemistrysteps.com/hydrolysis-of-lactones/)
Lactones hydrolyze faster than comparable straight-chain esters. Besides ring strain, the acceleration is attributed to distortion of the ester group, a loss of coplanarity, and a change in the rate-limiting step or mechanism[19](https://pmc.ncbi.nlm.nih.gov/articles/PMC10547131/). The same ring-opening tendency underlies their use in polymerization: an alkoxide generated under basic conditions opens the lactone ring and propagates the chain through successive ester formation[18](https://www.chemistrysteps.com/hydrolysis-of-lactones/).
## Ring-opening polymerization
[Ring-opening polymerization](https://www.edgepedia.org/ring-opening-polymerization) (ROP) of lactones is the principal industrial route to aliphatic polyesters. Lactide, the cyclic dimer of lactic acid, and ε-caprolactone are the most common monomers, giving poly(lactide) (PLA) and poly(ε-caprolactone) (PCL) respectively[5](https://pubs.acs.org/ascecg/article/9/32/10664/449887/From-Lab-to-Market-Current-Strategies-for-the). PLA has become one of the most widely produced biobased polymers as a substitute for commodity plastics from nonrenewable sources, although PLA-based polyols have a high glass transition temperature (56 °C) compared with conventional polyols (−60 °C), which makes PCL more suitable for some polyurethane applications[5](https://pubs.acs.org/ascecg/article/9/32/10664/449887/From-Lab-to-Market-Current-Strategies-for-the). Reviews cover the catalytic systems used for substituted δ-lactones, including organocatalysts, alkali metals, and metal complexes[20](https://pubs.rsc.org/en/content/articlelanding/2023/py/d3py00657c), and for γ-lactones, including Lewis and Brønsted acids, organic bases, alkali metal compounds, organometallic compounds, and cooperative bicomponent systems[21](https://doi.org/10.1016/j.progpolymsci.2020.101309). Enzymatic ROP has also been developed, with Candida antarctica lipase B extensively explored for ring-closing reactions and ring-opening polymerizations of small monomers such as ε-caprolactone[22](https://pubmed.ncbi.nlm.nih.gov/27805747/). A recurring limitation is functional diversity: polyesters from ROP have a limited property range because few functionalized lactone monomers are available[23](https://pubs.acs.org/iecred/article/56/15/4207/874621/New-Chemistry-in-Functional-Aliphatic-Polyesters).
## Lactones in nature
**Flavors and fragrances.** Many γ- and δ-lactones are responsible for creamy, fruity aromas such as peach and coconut[3](https://pubs.rsc.org/en/content/articlehtml/2026/py/d6py00239k). In peach (Prunus persica), γ-decalactone contributes most to the characteristic aroma, and amino acid substitutions in the enzyme ALCOHOL ACYLTRANSFERASE 1 (PpAAT1) account for undetectable γ-decalactone levels in the low-aroma cultivar Achutao; PpAAT1 from high-aroma cultivars catalyzes the conversion of 4-hydroxydecanoyl-coenzyme A into γ-decalactone more efficiently[7](https://pubmed.ncbi.nlm.nih.gov/32001520/). [Acyl-CoA oxidase](https://www.edgepedia.org/acyl-coa-oxidase) 1 is also involved in γ-decalactone release from peach mesocarp[24](https://pubmed.ncbi.nlm.nih.gov/28238071/).
**Chemical communication.** The lactone motif recurs in semiochemicals, the signal molecules of organisms: 40 of 436 structures in a recent overview of arthropod pheromones are lactones[6](https://pubs.rsc.org/en/content/articlehtml/2015/np/c5np00006h). Cyclization of a hydroxy acid precursor raises vapor pressure by a factor of 100 and the octanol/water partition coefficient by a factor of 1000, making the lactone far better suited as a volatile, membrane-permeable signal than the hydroxy acid, which is largely deprotonated at physiological pH[6](https://pubs.rsc.org/en/content/articlehtml/2015/np/c5np00006h). Examples include buibuilactone, a sex pheromone component of scarab beetles of the genus Anomala, and japonilure, used as the R-enantiomer by the Japanese beetle Popillia japonica while the S-enantiomer is produced by the Osaka beetle Anomala osakana, so each species is antagonized by the other's pheromone[6](https://pubs.rsc.org/en/content/articlehtml/2015/np/c5np00006h).
**Macrolides and other bioactive lactones.** Macrolides are polyketide natural products characterized by a lactone group; the term was introduced by Woodward in 1957 for antibiotics with 14-, 15-, and 16-membered rings and has since been extended to smaller and larger rings, up to the largest known natural macrolide, a 66-membered lactone[4](https://pubs.rsc.org/en/content/articlehtml/2022/np/d2np00025c). Clinically used macrolide antibiotics include erythromycin, clarithromycin, and azithromycin[25](https://pubs.rsc.org/en/content/articlehtml/2025/cs/d2cs00909a). Sesquiterpene lactones are a prominent group of plant secondary metabolites found predominantly in the [Asteraceae](https://www.edgepedia.org/asteraceae) family, with roles in plant defense against herbivory, as phytotoxins, and as environmental signaling molecules[26](https://arxiv.org/abs/2402.00548). β-Lactone natural products, with more than 30 core scaffolds described, show potent activity against bacteria, fungi, and human cancer cell lines[27](https://pubs.rsc.org/en/content/articlelanding/2019/np/c8np00052b/1000).
## References
1. [IUPAC Compendium of Chemical Terminology, lactones (L03439)](https://goldbook.iupac.org/terms/view/L03439)
2. [Lactone Formation, Virtual Textbook of Organic Chemistry (W. H. Reusch), OrganicChemistryData.org](https://organicchemistrydata.org/reusch/virtualtext/lactone-formation/)
3. [Polymers containing pendant lactone groups: synthesis and potential for sustainable materials, Polymer Chemistry (2026)](https://pubs.rsc.org/en/content/articlehtml/2026/py/d6py00239k)
4. [Fungal bioactive macrolides, Natural Product Reports (2022)](https://pubs.rsc.org/en/content/articlehtml/2022/np/d2np00025c)
5. [From Lab to Market: Current Strategies for the Production of Biobased Polyols, ACS Sustainable Chemistry & Engineering (2021)](https://pubs.acs.org/ascecg/article/9/32/10664/449887/From-Lab-to-Market-Current-Strategies-for-the)
6. [The use of the lactone motif in chemical communication, Natural Product Reports (2015)](https://pubs.rsc.org/en/content/articlehtml/2015/np/c5np00006h)
7. [Differences in PpAAT1 Activity in High- and Low-Aroma Peach Varieties Affect γ-Decalactone Production, PubMed (2020)](https://pubmed.ncbi.nlm.nih.gov/32001520/)
8. [Chem 263 lecture notes: Carboxylic Acids and Derivatives Nomenclature, University of Alberta](https://www.chem.ualberta.ca/~vederas/Chem_263/outlines/pdf/Chem263_Nov26_2013%20notes.pdf)
9. [Lecture 13, Pomona College Chemistry 110](https://pages.pomona.edu/~djo04747/110/Lecture_13_2020.pdf)
10. [Naming and Indexing of Chemical Substances for Chemical Abstracts, CAS](https://www.cas.org/sites/default/files/documents/indexguideapp.pdf)
11. [IUPAC Provisional Recommendations, Chapter 6, Sect 65: Preferred IUPAC Names](https://media.iupac.org/reports/provisional/abstract04/BB-prs310305/Chapter6-Sec65.pdf)
12. [Gamma-Butyrolactone, PubChem CID 7302](https://pubchem.ncbi.nlm.nih.gov/compound/oxolan-2-one)
13. [Natural ten-membered lactones: sources, structural diversity, biological activity, Natural Product Reports (2024)](https://pubs.rsc.org/en/content/articlehtml/2024/np/d3np00013c)
14. [Chapter 22 course text excerpt, University of California, Irvine](https://www.chem.uci.edu/files/smith_textbook/smi96656_c22_001_036.pdf)
15. [Thesis, NC State University repository: lactone formation in dairy systems](https://repository.lib.ncsu.edu/bitstreams/3fb171ec-b028-4ecf-bc2b-4953e0a9b3d2/download)
16. [Alicyclic, alicyclic-fused and aromatic-fused ring lactones, JECFA Monograph 52 (2004)](https://inchem.org/documents/jecfa/jecmono/v52je13.htm)
17. [Brief Overview of Drug Degradation Chemistry, Wiley book excerpt](https://catalogimages.wiley.com/images/db/pdf/9781118832936.excerpt.pdf)
18. [Hydrolysis of Lactones, Chemistry Steps](https://www.chemistrysteps.com/hydrolysis-of-lactones/)
19. [A multiple linear regression approach to the estimation of carboxylic acid ester and lactone alkaline hydrolysis rate constants, PMC (2023)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10547131/)
20. [Sourcing, thermodynamics, and ring-opening (co)polymerization of substituted δ-lactones: a review, Polymer Chemistry (2023)](https://pubs.rsc.org/en/content/articlelanding/2023/py/d3py00657c)
21. [Ring-opening polymerization of γ-lactones and copolymerization with other cyclic monomers, Progress in Polymer Science (2020)](https://doi.org/10.1016/j.progpolymsci.2020.101309)
22. [Recent Developments and Optimization of Lipase-Catalyzed Lactone Formation and Ring-Opening Polymerization, PubMed (2016)](https://pubmed.ncbi.nlm.nih.gov/27805747/)
23. [New Chemistry in Functional Aliphatic Polyesters, Industrial & Engineering Chemistry Research (2017)](https://pubs.acs.org/iecred/article/56/15/4207/874621/New-Chemistry-in-Functional-Aliphatic-Polyesters)
24. [Acyl-CoA oxidase 1 is involved in γ-decalactone release from peach fruit, PubMed (2017)](https://pubmed.ncbi.nlm.nih.gov/28238071/)
25. [Cyclic natural product oligomers: diversity and (bio)synthesis of macrocycles, Chemical Society Reviews (2025)](https://pubs.rsc.org/en/content/articlehtml/2025/cs/d2cs00909a)
26. [Plant sesquiterpene lactones, arXiv (2024)](https://arxiv.org/abs/2402.00548)
27. [Biosynthesis and chemical diversity of β-lactone natural products, Natural Product Reports (2019)](https://pubs.rsc.org/en/content/articlelanding/2019/np/c8np00052b/1000)
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*Topic: Encyclopedia › Physical world and mathematics › Chemistry › Organic substances › Carbonyl and carboxyl chemistry › Carboxylic acid derivatives › Esters › Esters by acyl residue › Lactate, glycolate, and other alpha-hydroxyacyl esters*
*Initially written Sep 17, 2026 · Reviewed: Sep 30, 2026; Oct 15, 2026 · Edited: Sep 30, 2026; Oct 15, 2026 · Last review: Oct 15, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license