(6Z,9Z,12Z)-6,9,12-Octadecatrienoic acid methyl ester
[CAS# 16326-32-2]

Identification

• Classification: Analytical chemistry >> Standard >> Food and beverage standards
• Name: (6Z,9Z,12Z)-6,9,12-Octadecatrienoic acid methyl ester
• Synonyms: Methyl octadeca-6,9,12-trienoate; Methyl gamma-linolenate
• Molecular Formula: C₁₉H₃₂O₂
• Molecular Weight: 292.46
• CAS Registry Number: 16326-32-2
• EC Number: 680-551-7
• SMILES: CCCCC/C=C\C/C=C\C/C=C\CCCCC(=O)OC

Properties

• Solubility: Insoluble (3.8E^-3 g/L) (25 ºC), Calc.^*
• Density: 0.895±0.06 g/cm³ (20 ºC 760 Torr), Calc.^*
• Boiling point: 385.4±0.0 ºC (760 Torr), Calc.^*
• Flash point: 101.5±23.2 ºC, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2014 ACD/Labs)

Safety Data

• Hazard Symbols: GHS02;GHS07 Danger
• Hazard Statements: H225-H319
• Precautionary Statements: P210-P280-P305+P351+P338-P337+P313-P403+P235
• Transport Information: UN 1993 / PGIII

Discovory and Applicatios

(6Z,9Z,12Z)-6,9,12-Octadecatrienoic acid methyl ester is a methyl ester derivative of an 18-carbon polyunsaturated fatty acid with three cis double bonds located at the 6th, 9th, and 12th carbon atoms. This compound is one of several isomers of octadecatrienoic acid methyl esters, and its structure corresponds to the methyl ester of gamma-linolenic acid (GLA), a fatty acid known for its significant role in biological and industrial applications.

The discovery and characterization of (6Z,9Z,12Z)-6,9,12-octadecatrienoic acid methyl ester emerged from research on natural lipids, particularly those found in seed oils of certain plants such as evening primrose (Oenothera biennis), borage (Borago officinalis), and blackcurrant (Ribes nigrum). These plants are known to be rich sources of gamma-linolenic acid. In analytical chemistry, the methyl esterification of fatty acids, including GLA, is a standard process used to improve volatility and stability for chromatographic analysis, mainly gas chromatography coupled with mass spectrometry (GC-MS). This method enables precise identification and quantification of fatty acids in complex biological and food matrices.

The methyl ester derivative is often employed as a reference standard in lipid profiling due to its well-defined chemical and chromatographic properties. This facilitates accurate determination of gamma-linolenic acid content in nutritional supplements, pharmaceuticals, and food products. Methyl esters like (6Z,9Z,12Z)-6,9,12-octadecatrienoic acid methyl ester are more convenient for analytical purposes than free fatty acids because the ester form has a lower boiling point and greater thermal stability.

In terms of biological importance, the parent acid, gamma-linolenic acid, plays a crucial role in human health. GLA is a precursor to important eicosanoids, signaling molecules involved in inflammatory and immune responses. It is converted enzymatically into dihomo-gamma-linolenic acid (DGLA), which subsequently acts as a substrate for the synthesis of anti-inflammatory prostaglandins. Dietary supplementation with GLA has been studied for its potential benefits in treating conditions such as atopic dermatitis, rheumatoid arthritis, diabetic neuropathy, and other inflammatory diseases.

While the methyl ester itself is not directly used in biological systems, it serves as a critical intermediate for chemical modifications and delivery systems in pharmaceutical formulations. For example, methyl esters of fatty acids can be used to produce structured lipids and conjugates that enhance bioavailability or target specific tissues.

Industrial applications of (6Z,9Z,12Z)-6,9,12-octadecatrienoic acid methyl ester and related methyl esters are diverse. In the biodiesel industry, methyl esters of fatty acids—commonly referred to as fatty acid methyl esters (FAMEs)—are the principal components of biodiesel fuels. The presence of polyunsaturated methyl esters like this one affects fuel properties such as cold flow behavior, oxidative stability, and combustion efficiency. The degree of unsaturation contributes to lower cloud points but can also lead to faster oxidation and rancidity, making the balance of saturated and unsaturated esters critical for biodiesel quality.

Beyond fuels, these methyl esters are valuable as intermediates in the synthesis of biopolymers, lubricants, surfactants, and plasticizers. Their biodegradable and renewable nature makes them attractive alternatives to petrochemical-derived compounds in green chemistry and sustainable materials.

The production of (6Z,9Z,12Z)-6,9,12-octadecatrienoic acid methyl ester can be achieved through direct esterification of gamma-linolenic acid with methanol under acidic or enzymatic catalysis. Additionally, chemical synthesis routes exist to generate this compound, particularly when high purity or specific isotopic labeling is required for research.

In research contexts, this methyl ester is used in studies exploring lipid metabolism, enzyme specificity, and the biological effects of polyunsaturated fatty acids. It also serves as a model compound for investigating oxidative stability and degradation pathways of unsaturated lipids, which is important for both food science and pharmacology.

Overall, (6Z,9Z,12Z)-6,9,12-octadecatrienoic acid methyl ester is a well-characterized compound central to the analysis and application of gamma-linolenic acid. It bridges fundamental biochemical research, clinical nutrition, and various industrial fields, highlighting the importance of fatty acid methyl esters in modern science and technology. Its role in enabling accurate fatty acid profiling and serving as a renewable chemical building block underscores its broad relevance.

References

2010. Antimicrobial activity of n-6, n-7 and n-9 fatty acids and their esters for oral microorganisms. Archives of Oral Biology, 55(8).
DOI: 10.1016/j.archoralbio.2010.05.009

2011. Echium acanthocarpum hairy root cultures, a suitable system for polyunsaturated fatty acid studies and production. BMC Biotechnology, 11.
DOI: 10.1186/1472-6750-11-42

2024. Characterization of fatty acid composition in wax produced by grapevine mealybug, Maconellicoccus hirsutus (Green). International Journal of Tropical Insect Science, 44.
DOI: 10.1007/s42690-024-01311-8