506-32-1

Basic information

• Product Name: Arachidonic acid
• Synonyms: (5Z,8Z,11Z,14Z)-5,8,11,14-Icosatetraenoic acid;(all-Z)-5,8,11,14-Eicosatetraenoic acid;(all-z)-5,8,11,14-eicosatetraenoicacid;5,8,11,14-Eicosatetraenoic acid, (all-Z)-;Arachidonate;5,8,11,14-ALL-CIS-EICOSATETRAENOIC ACID;5,8,11,14-EICOSATETRAENOIC ACID;5,8,11,14-EICOSATETRENOIC ACID
• CAS NO: 506-32-1
• Molecular Formula: C₂₀H₃₂O₂
• Molecular Weight: 304.47
• EINECS: 208-033-4
• Product Categories: Industrial/Fine Chemicals;Fatty & Aliphatic Acids, Esters, Alcohols & Derivatives;Mixed Fatty Acids;Higher Fatty Acids & Higher Alcohols;Unsaturated Higher Fatty Acids;Biochemistry;Fatty Acid Derivatives & Lipids;Glycerols;Arachidonic Acid;Arachidonic Acid Cascade;Fatty Acid Metabolism;Functional Foods;Lipids in Cell Signaling;Omega 6 fatty acids and derivatives;Polyunsaturated Fatty Acids (PUFAs) and Omega-3 Fatty Acids;AN-AZ;Bioactive Small Molecules;Biochemicals and Reagents;Building Blocks;C13 to C42+;Carbonyl Compounds;Carboxylic Acids;Cell Biology;Cell Signaling and Neuroscience;Chemical Synthesis;Fatty Acids and conjugates;Fatty Acyls;Lipids;Metabolic Pathways;Metabolomics;Nutrition Research;Organic Building Blocks;Polyunsaturated;Unsaturated Fatty Acids and Derivatives;API intermediate
• Mol File: 506-32-1.mol
• Article Data: 23

Chemical Properties

• Melting Point: −49 °C(lit.)
• Boiling Point: 169-171 °C0.15 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: colorless to light yellow/oil
• Density: 0.922 g/mL at 25 °C(lit.)
• Vapor Pressure: 8.85E-08mmHg at 25°C
• Refractive Index: n20/D 1.4872(lit.)
• Storage Temp.: −20°C
• Solubility: ethanol: ≥10 mg/mL
• PKA: 4.75±0.10(Predicted)
• Water Solubility: PRACTICALLY INSOLUBLE
• Stability: Light Sensitive, Temperature Sensitive
• Merck: 14,765
• BRN: 1713889
• CAS DataBase Reference: Arachidonic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Arachidonic acid(506-32-1)
• EPA Substance Registry System: Arachidonic acid(506-32-1)

Safety Data

• Statements: 19
• Safety Statements: 24/25-19
• RIDADR: UN1170 - class 3 - PG 2 - Ethanol
• WGK Germany: 3
• RTECS: CE6675000
• F: 8-10-23
• Hazardous Substances Data: 506-32-1(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 506-32-1 differently. You can refer to the following data:
1. Arachidonic acid belongs to a kind of polyunsaturated omega-6 fatty acid, which is highly biologically relevant. It is abundantly distributed in brain, muscles and liver. It is the precursor for all prostaglandins, thromboxanes, and leukotrienes. Most cellular arachidonic acid is esterified in the membrane phospholipids. It is an important second messenger of cellular signalling participating in the regulation of signaling enzymes including PLC-γ, PLC-δ, and PKC-α, -β, and -γ isoforms. In addition, arachidonic acid acts as key inflammatory intermediate as well as avasodilator. Generally, the body can synthesize the arachidonic acid through linoleic acid. However, upon linoleic acid deficiency, it is necessary to supplement arachidonic acid from the diets. Food sources of arachidonic acid include meat, eggs and some fishes. Alternatively, we can also have arachidonic acid supplements.
2. Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6). It is the counterpart to the saturated arachidic acid found in peanut oil, (L. arachis – peanut.).

References

http://www.fitday.com/fitness-articles/nutrition/healthy-eating/what-is-arachidonic-acid.html https://en.wikipedia.org/wiki/Arachidonic_acid https://www.caymanchem.com/product/90010

Chemical Properties

Different sources of media describe the Chemical Properties of 506-32-1 differently. You can refer to the following data:
1. In chemical structure, arachidonic acid is a carboxylic acid with a 20-carbon chain and four cis-double bonds; the first double bond is located at the sixth carbon from the omega end. Some chemistry sources define 'arachidonic acid' to designate any of the eicosatetraenoic acids. However, almost all writings in biology, medicine and nutrition limit the term to all-cis-5,8,11,14- eicosatetraenoic acid.
2. liquid

Uses

Different sources of media describe the Uses of 506-32-1 differently. You can refer to the following data:
1. An unsaturated omega-6 fatty acid constituent of the phospholipids of cell membranes
2. Arachidonic Acid is an essential fatty acid and a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. Arachidonic Acid occurs in liver, brain, glandular organs, and depot fats of animals, in small amounts in human depot fats, and Arachidonic Acid is also a constituent of animal phosphatides.
3. arachidonic acid is an ingredient with skin-smoothing, emollient, and healing properties. Arachidonic acid is an omega-6 essential fatty acid naturally occurring in the skin and considered critical for appropriate skin metabolism. It is a constituent of vitamin F.

Definition

ChEBI: A long-chain fatty acid that is a C20, polyunsaturated fatty acid having four (Z)-double bonds at positions 5, 8, 11 and 14.

General Description

A Certified Spiking Solution? suitable for use in mass spectrometry-based fatty acid testing applications such as assessment of cardiovascular disease risk and fatty acid deficiency, and detection and quantification of arachidonic acid in nutraceuticals and dietary supplements. Arachidonic acid (cis-5,8,11,14), sometimes referred to as AA or ARA, is a polyunsaturated omega-6 fatty acid. Studies suggests that ARA as well as other fatty acids can serve as biomarkers for cardiovascular disease, and nutritional and metabolic disorders.

Biological Activity

Endogenous free fatty acid released from phospholipids by phospholipase A 2 . Important cellular signaling mediator and precursor of eicosanoids. Metabolized by lipoxygenases, cyclooxygenases and cytochrome P450 monooxygenases.

Biochem/physiol Actions

Arachidonic acid stimulates adhesion of MDA-MB-435 human metastatic cancer cells to extracellular matrix molecules (collagen IV and vitronectin) .

Safety Profile

Poison by intravenous route.Experimental reproductive effects. Mutation datareported. When heated to decomposition it emits acridsmoke and irritating fumes.

Carcinogenicity

In vitro and in vivo studies indicate that inhibition of arachidonic acid metabolism inhibits the growth of malignant cells, including head and neck squamous cell carcinoma, and implicates arachadonic acid in facilitating the metastasis of these tumor cells. Arachidonic acid reaction with cyclooxygenase and lipoxygenases yield eicosanoids that can mediate prostate cancer proliferation and enhance both tumor vascularization and metastasis. Cytochrome P450 arachidonic acid epoxygenases promote cell proliferation and inhibit apoptosis in endothelial cells.

InChI:InChI=1/C20H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h6-7,9-10,12-13,15-16H,2-5,8,11,14,17-19H2,1H3,(H,21,22)/b7-6+,10-9+,13-12+,16-15+

Synthetic route

ethyl arachidonate (95285-77-1, 1808-26-0) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
With triethylamine In water; acetonitrile at 30℃; under 7500600 Torr; for 96h;	78%
With potassium hydroxide

eicosa-5,8,11,14-tetraynoic acid (1191-85-1) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
With sodium tetrahydroborate; hydrogen; ethylenediamine; nickel diacetate In ethanol at 20℃;	34%
With hydrogen; Lindlar's catalyst In methanol
With quinoline; water; hydrogen; Lindlar's catalyst 1.) AcOEt; Yield given. Multistep reaction;

arachidonic acid methyl ester (38575-18-7) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
With potassium hydroxide; ethanol

1-chloro-nonadeca-4c,7c,10c,13c-tetraene (612852-05-8) + carbon dioxide (124-38-9) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
(i) EtMgBr, Et2O, (ii) /BRN= 1900390/, Et2O; Multistep reaction;

carbon dioxide (124-38-9) + C19H31ClMg → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
In tetrahydrofuran

2-trans-Alken-5,8,11,14-eicosatetrainsaeure (40924-42-3) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
With pyridine; hydrogen; Lindlar's catalyst In ethyl acetate

(3Z,6Z)-1-oxo-dodecadienal (13553-09-8) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
With sodium hexamethyldisilazane 1.) THF, HMPA, RT, 2 h, 2.) from -100 to 0 deg C, 4 h; Multistep reaction;

(5Z,8Z,11Z,14Z)-20-hydroxyeicosa-5,8,11,14-tetraenoic acid methyl ester (86179-96-6) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
With lithium aluminium tetrahydride 1.) tosylation;; Multistep reaction;

arachidonic acid TMS ester (113516-18-0) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
With sodium thiosulfate In water Yield given;

(5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetraenoic acid isobutyl ester (119520-63-7) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
With sodium hydroxide In ethanol for 12h; Ambient temperature; Yield given;

cetyl arachidonate → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
With potassium hydroxide for 4h; Heating;	40 mg

arachidonic acid octabromide → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
With ethanol beim Erhitzen mit verkupfertem Zink-Staub;

eicosa-5,8,11,14-tetraynoic acid → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
With quinoline; Petroleum ether Hydrogenation.an Lindlar-Katalysator;
With methanol Hydrogenation.an Lindlar-Katalysator;

1-Heptyne (628-71-7) + HgO → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + KMnO4

Conditions

Yield

Multi-step reaction with 9 steps 1: K2CO3, NaI, CuI / dimethylformamide / 4 h / 20 °C 2: K2CO3 / methanol / 4 h / 20 °C 3: 81.9 percent / PPh3, CBr4 / CH2Cl2 / 0.67 h / 0 °C 4: K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 5: p-toluenesulfonic acid / methanol / 1 h / 20 °C 6: 79.2 percent / PPh3, CBr4 / CH2Cl2 / 0.67 h / 0 °C 7: 0.89 g / K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 8: 66.3 percent / 5percent aq. NaOH / methanol / 3 h / 20 °C 9: 1.) H2, quinoline, 2.) H2O / 1.) Lindlar's cat. / 1.) AcOEt View Scheme

5-hexynonitrile (14918-21-9) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + KMnO4

Conditions	Yield
Multi-step reaction with 4 steps 1: 75.5 percent / gaseous HCl / methanol; H2O / 6 h / 60 °C 2: 0.89 g / K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 3: 66.3 percent / 5percent aq. NaOH / methanol / 3 h / 20 °C 4: 1.) H2, quinoline, 2.) H2O / 1.) Lindlar's cat. / 1.) AcOEt View Scheme

methyl hex-5-ynoate (77758-51-1) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + KMnO4

Conditions	Yield
Multi-step reaction with 3 steps 1: 0.89 g / K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 2: 66.3 percent / 5percent aq. NaOH / methanol / 3 h / 20 °C 3: 1.) H2, quinoline, 2.) H2O / 1.) Lindlar's cat. / 1.) AcOEt View Scheme

undeca-2,5-diyn-1-ol (35378-79-1) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + KMnO4

Conditions

Yield

Multi-step reaction with 7 steps 1: 81.9 percent / PPh3, CBr4 / CH2Cl2 / 0.67 h / 0 °C 2: K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 3: p-toluenesulfonic acid / methanol / 1 h / 20 °C 4: 79.2 percent / PPh3, CBr4 / CH2Cl2 / 0.67 h / 0 °C 5: 0.89 g / K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 6: 66.3 percent / 5percent aq. NaOH / methanol / 3 h / 20 °C 7: 1.) H2, quinoline, 2.) H2O / 1.) Lindlar's cat. / 1.) AcOEt View Scheme

1-bromo-2,5-undecadiyne (34498-24-3) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + KMnO4

Conditions	Yield
Multi-step reaction with 6 steps 1: K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 2: p-toluenesulfonic acid / methanol / 1 h / 20 °C 3: 79.2 percent / PPh3, CBr4 / CH2Cl2 / 0.67 h / 0 °C 4: 0.89 g / K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 5: 66.3 percent / 5percent aq. NaOH / methanol / 3 h / 20 °C 6: 1.) H2, quinoline, 2.) H2O / 1.) Lindlar's cat. / 1.) AcOEt View Scheme

1-bromo-2,5,8-tetradecatriyne (34498-26-5) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + KMnO4

Conditions	Yield
Multi-step reaction with 3 steps 1: 0.89 g / K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 2: 66.3 percent / 5percent aq. NaOH / methanol / 3 h / 20 °C 3: 1.) H2, quinoline, 2.) H2O / 1.) Lindlar's cat. / 1.) AcOEt View Scheme

1-hydroxy-2,5,8-tetradecatriyne (35378-84-8) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + KMnO4

Conditions	Yield
Multi-step reaction with 4 steps 1: 79.2 percent / PPh3, CBr4 / CH2Cl2 / 0.67 h / 0 °C 2: 0.89 g / K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 3: 66.3 percent / 5percent aq. NaOH / methanol / 3 h / 20 °C 4: 1.) H2, quinoline, 2.) H2O / 1.) Lindlar's cat. / 1.) AcOEt View Scheme

Eicosa-5,8,11,14-tetrain-1-saeuremethylester (102471-97-6) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + KMnO4

Conditions	Yield
Multi-step reaction with 2 steps 1: 66.3 percent / 5percent aq. NaOH / methanol / 3 h / 20 °C 2: 1.) H2, quinoline, 2.) H2O / 1.) Lindlar's cat. / 1.) AcOEt View Scheme

2-Tetradeca-2,5,8-triynyloxy-tetrahydro-furan → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + KMnO4

Conditions	Yield
Multi-step reaction with 5 steps 1: p-toluenesulfonic acid / methanol / 1 h / 20 °C 2: 79.2 percent / PPh3, CBr4 / CH2Cl2 / 0.67 h / 0 °C 3: 0.89 g / K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 4: 66.3 percent / 5percent aq. NaOH / methanol / 3 h / 20 °C 5: 1.) H2, quinoline, 2.) H2O / 1.) Lindlar's cat. / 1.) AcOEt View Scheme

Benzoic acid undeca-2,5-diynyl ester → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + KMnO4

Conditions

Yield

Multi-step reaction with 8 steps 1: K2CO3 / methanol / 4 h / 20 °C 2: 81.9 percent / PPh3, CBr4 / CH2Cl2 / 0.67 h / 0 °C 3: K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 4: p-toluenesulfonic acid / methanol / 1 h / 20 °C 5: 79.2 percent / PPh3, CBr4 / CH2Cl2 / 0.67 h / 0 °C 6: 0.89 g / K2CO3, NaI, CuI / dimethylformamide / 5 h / 20 °C 7: 66.3 percent / 5percent aq. NaOH / methanol / 3 h / 20 °C 8: 1.) H2, quinoline, 2.) H2O / 1.) Lindlar's cat. / 1.) AcOEt View Scheme

(Z)-3-nonenal (31823-43-5) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) NaN(SiMe3)2 / 1.) THF, toluene, RT, 1 h, 2.) from -100 to 0 deg C, 4 h 2: 0.1 M aq. p-toluenesulfonic acid / tetrahydrofuran / 0.3 h / Heating 3: 1.) NaN(SiMe3)2 / 1.) THF, HMPA, RT, 2 h, 2.) from -100 to 0 deg C, 4 h View Scheme

(Z)-3-nonenal diisopropyl acetal (120018-49-7) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 0.1 M aq. p-toluenesulfonic acid / tetrahydrofuran / 0.3 h / Heating 2: 1.) NaN(SiMe3)2 / 1.) THF, toluene, RT, 1 h, 2.) from -100 to 0 deg C, 4 h 3: 0.1 M aq. p-toluenesulfonic acid / tetrahydrofuran / 0.3 h / Heating 4: 1.) NaN(SiMe3)2 / 1.) THF, HMPA, RT, 2 h, 2.) from -100 to 0 deg C, 4 h View Scheme

(Z,Z)-3,6-dodecadienal diisopropyl acetal (117203-38-0) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 0.1 M aq. p-toluenesulfonic acid / tetrahydrofuran / 0.3 h / Heating 2: 1.) NaN(SiMe3)2 / 1.) THF, HMPA, RT, 2 h, 2.) from -100 to 0 deg C, 4 h View Scheme

hexanal (66-25-1) + magnesium aluminium-isopropylate → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions

Yield

Multi-step reaction with 5 steps 1: 1.) NaN(SiMe3)2 / 1.) THF, toluene, RT, 1 h, 2.) from -100 to 0 deg C, 4 h 2: 0.1 M aq. p-toluenesulfonic acid / tetrahydrofuran / 0.3 h / Heating 3: 1.) NaN(SiMe3)2 / 1.) THF, toluene, RT, 1 h, 2.) from -100 to 0 deg C, 4 h 4: 0.1 M aq. p-toluenesulfonic acid / tetrahydrofuran / 0.3 h / Heating 5: 1.) NaN(SiMe3)2 / 1.) THF, HMPA, RT, 2 h, 2.) from -100 to 0 deg C, 4 h View Scheme

N-(p-nitrophenyl)-arachidonamide (119520-58-0) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) phosgene, 2.) pyridine / 1.) CH2Cl2, 0 deg C, 2.) CH2Cl2, rt, 30 min, 3.) CH2Cl2, 3 h 2: 3 N aq. NaOH / ethanol / 12 h / Ambient temperature View Scheme

6-chloro-1-hexanol (2009-83-8) → all cis 5,8,11,14-eicosatetraenoic acid (506-32-1)

Conditions

Yield

Multi-step reaction with 5 steps 1: sodium iodide / acetone / 8 h / Heating 2: potassium carbonate / acetonitrile / 10 h / Heating 3: 2.) n-BuLi / tetrahydrofuran / 0.5 h / -78 - -30 °C / 1.) acetonitrile, reflux, 10 h; 2.) THF, from -78 deg C to -30 deg C, 30 min 4: hexamethylphosphoric acid triamide / 1.) -78 deg C, 30 min; 2.) from -78 deg C to 0 deg C, 90 min 5: 2.) lithium aluminum hydride / 1.) tosylation; View Scheme

diazomethane (186581-53-3, 908094-01-9) + all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) → methyl arachidonate (2566-89-4)

Conditions	Yield
In methanol at 0℃; for 0.333333h;	100%
In diethyl ether
In diethyl ether at 0℃; Yield given;

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) → arachidonyl alcohol (13487-46-2)

Conditions	Yield
With lithium aluminium tetrahydride In diethyl ether 1.) 30 min, 10 deg C, 2.) 30 min, reflux;	100%
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;	99%
Stage #1: all cis 5,8,11,14-eicosatetraenoic acid With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere; Stage #2: With water; sodium hydroxide In tetrahydrofuran for 1h;	99%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) → cis-14,15-epoxyeicosatrienoic acid (197508-62-6)

Conditions	Yield
With human recombinant cytochrome P450 2E1 Enzymatic reaction; stereoselective reaction;	100%
With dihydrogen peroxide; sodium sulfate In diethyl ether
Multi-step reaction with 2 steps 1.1: CH2Cl2 / 0.33 h 2.1: H2O2; sodium imidazolate / CH2Cl2; diethyl ether / 0.05 h / 20 °C 2.2: KHSO4 / CH2Cl2; diethyl ether / 0.05 h / 20 °C View Scheme

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + 3-O-stearoyl-1-O-(tert-butyl-dimethyl-silanyl)-sn-glycerol (1360614-23-8) → 2-O-arachidonoyl-3-O-(tert-butyldimethylsilyl)-1-O-stearoyl-sn-glycerol (1363901-86-3)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere; Darkness;	99%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide Inert atmosphere; Darkness;	99%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + 3-(5-methyl-4-(trifluoromethyl)thiazol-2-yl)bicyclo[1.1.1]pentan-1-amine hydrochloride → (5Z,8Z,11Z,14Z)-N-(3-(5-methyl-4-(trifluoromethyl)thiazol-2-yl)bicyclo[1.1.1]pentan-1-yl)icosa-5,8,11,14-tetraenamide

Conditions	Yield
With pyridine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.5h;	99%

1,3-dibutanoyloxy-2-propanol (17364-00-0) + all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) → 2-((5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyloxy)propane-1,3-diyl dibutyrate (1274596-36-9)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran; dichloromethane at 0℃; for 4h;	98%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h;	88%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; Inert atmosphere;	72%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) → 6-((3Z,6Z,9Z)-1-iodopentadeca-3,6,9-trien-1-yl)tetrahydro-2Hpyran-2-one (742103-77-1)

Conditions	Yield
With 2,6-dimethylpyridine; iodine In dichloromethane at 0℃; for 15h; Inert atmosphere; Cooling with ice;	96%
With 2,4,6-trimethyl-pyridine; iodine In dichloromethane at 0℃; for 14h;	83%
With potassium hydrogencarbonate In ethanol; hexane; water at 24℃; for 16h;	62%
With potassium triiodide; potassium hydrogencarbonate In tetrahydrofuran; water at 0℃;
With iodine; sodium hydrogencarbonate In ethanol	5 g

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + ethanolamine (141-43-5) → anandamide (94421-68-8)

Conditions	Yield
Stage #1: all cis 5,8,11,14-eicosatetraenoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 0.5h; Stage #2: ethanolamine In dichloromethane for 12h;	96%
Stage #1: all cis 5,8,11,14-eicosatetraenoic acid With 1-[(1-(cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino)]-uronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; acetonitrile at 20℃; for 0.166667h; Inert atmosphere; Stage #2: ethanolamine In dichloromethane; acetonitrile at 20℃; Inert atmosphere;	85%
With Candida antarctica lipase B In hexane at 50℃; for 6h; Inert atmosphere; Enzymatic reaction;	72.7%

(E)-N-methoxy-N-methyloctadec-9-enamide (288862-96-4) + all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) → N-Methoxy-N-methyl-arachidonamide (229021-66-3)

Conditions	Yield
	96%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethylamine (134179-38-7) → N-{{[(azidoethoxy)ethoxy]ethoxy}ethyl}arachidonoylamide (1391826-57-5)

Conditions	Yield
Stage #1: all cis 5,8,11,14-eicosatetraenoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.166667h; Inert atmosphere; Stage #2: With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 0.5h; Inert atmosphere; Stage #3: 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethylamine In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere;	96%
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;

N-hydroxyphthalimide (524-38-9) + all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) → 1,3-dioxoisoindolin-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate

Conditions	Yield
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 14h;	96%
With dmap; diisopropyl-carbodiimide In dichloromethane

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + glycine (56-40-6) → N-arachidonoylglycine (179113-91-8)

Conditions	Yield
Stage #1: all cis 5,8,11,14-eicosatetraenoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 0.5h; Stage #2: glycine In dichloromethane for 12h;	96%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + vanillylamine hydrochloride (7149-10-2) → arvanil (128007-31-8)

Conditions	Yield
With diethyl cyanophosphonate; triethylamine In tetrahydrofuran for 1.5h;	95%
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In dichloromethane; ethyl acetate at 0℃; for 0.25h;	79%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + oxiranyl-methanol (556-52-5) → oxiran-2-ylmethyl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate (439146-24-4)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h;	95%
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;	42%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + 15-azido-14,14-bis(azidomethyl)-3,6,9,12-tetraoxapentadecan-1-amine → N-(15-azido-14,14-bis(azidomethyl)-3,6,9,12-tetraoxapentadecan)arachidonoylamide

Conditions	Yield
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 35℃; for 16h; Inert atmosphere;	95%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + 1,3-Bis-triisopropylsilanyloxy-propan-2-ol (98264-26-7) → (5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetraenoic acid 2-triisopropylsilanyloxy-1-triisopropylsilanyloxymethyl-ethyl ester (223259-26-5)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 24h; Ambient temperature;	94%

C37H60O4Si (1037195-40-6) + all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) → C57H90O5Si (1037195-83-7)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane	94%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + 3-O-[2',3',4',6'-tetracetyl-β-galactose]-1-[6''-pyreneacetamidohexanoyl]glycerol → C61H77NO15

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; Inert atmosphere;	93%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + cholesterol (57-88-5) → cholesteryl 5,8,11,14-eicosatetraenoate (604-34-2)

Conditions	Yield
With pseudomonas lipase In water at 40℃; for 24h; Esterification; Enzymatic reaction;	92.1%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) → (5Z,8Z,11Z,13E)-15(S)-hydroperoxyeicosa-5,8,11,13-tetraenoic acid (70981-96-3)

Conditions	Yield
With ammonium sulfate soybean lipoxygenase;	92%
With soybean lipoxygenase; oxygen at 23℃; Km and Vmax value at pH=9.2;
With ammonium hydroxide (enzymatic oxidation);

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + 1-(1’-β-D-[2’,3’,4’,6’-tetracetyl]galactosyl)glycerol (28069-18-3) → C37H56O13 (1613026-83-7)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; Inert atmosphere;	92%

6-nitroveratryl alcohol (1016-58-6) + all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) → 4,5-dimethoxy-2-nitrobenzyl arachidonate (1446428-04-1)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Inert atmosphere;	91%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + benzylamine (100-46-9) → N-benzylicosa-5Z,8Z,11Z,14Z-tetraenamide

Conditions	Yield
Stage #1: all cis 5,8,11,14-eicosatetraenoic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.25h; Inert atmosphere; Stage #2: benzylamine In dichloromethane Inert atmosphere;	91%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + isobutyl chloroformate (543-27-1) → arachidonoyl isobutyl carbonate

Conditions	Yield
With triethylamine In acetonitrile at 0℃; for 0.333333h; Inert atmosphere;	90%
With triethylamine In acetonitrile at 0 - 4℃; for 0.333333h;
With 4-methyl-morpholine In acetonitrile at 0℃; for 0.666667h;
With 4-methyl-morpholine; triethylamine In tetrahydrofuran at -15℃; for 0.25h;
With triethylamine In acetone at 20℃; for 0.5h; Inert atmosphere;

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + 2-chloroethanamine hydrochloride (870-24-6) → arachidonoyl-2-chloroethylamide

Conditions	Yield
Stage #1: all cis 5,8,11,14-eicosatetraenoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 1h; Stage #2: 2-chloroethanamine hydrochloride With pyridine In dichloromethane at 0 - 20℃; for 0.5h;	90%
Stage #1: all cis 5,8,11,14-eicosatetraenoic acid With triethylamine; isobutyl chloroformate In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 2-chloroethanamine hydrochloride With triethylamine In tetrahydrofuran at 0℃; for 3.5h;	80%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + combrestatin A4 (117048-62-1, 117048-59-6) → C38H50O6

Conditions	Yield
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; Inert atmosphere;	90%

3-METHOXYBENZYLAMINE (5071-96-5) + all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) → O 1986

Conditions	Yield
Stage #1: all cis 5,8,11,14-eicosatetraenoic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.25h; Inert atmosphere; Stage #2: 3-METHOXYBENZYLAMINE In dichloromethane Inert atmosphere;	90%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + (R)-4-(phenylmethyl)-2-oxazolidinone (40217-17-2, 90719-32-7, 120574-96-1, 102029-44-7) → (R)-N-arachidonyl-4-benzyl-2-oxazolidinone (372504-81-9)

Conditions	Yield
Stage #1: all cis 5,8,11,14-eicosatetraenoic acid With pivaloyl chloride; triethylamine In tetrahydrofuran at -78 - 0℃; for 0.666667h; Stage #2: (R)-4-(phenylmethyl)-2-oxazolidinone With n-butyllithium In tetrahydrofuran at -78 - 0℃; for 3.5h;	88%

all cis 5,8,11,14-eicosatetraenoic acid (506-32-1) + 2-(3,4-dimethoxyphenyl)-ethylamine (120-20-7) → (5Z,8Z,11Z,14Z)-N-[2-(3,4-dimethoxyphenyl)ethyl]eicosa-5,8,11,14-tetraenamide (869881-08-3)

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine In tetrahydrofuran at 20℃; for 12h;	88%
Stage #1: all cis 5,8,11,14-eicosatetraenoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 20℃; for 0.166667h; Stage #2: 2-(3,4-dimethoxyphenyl)-ethylamine With triethylamine at 20℃;	76%

Upstream product

• 38575-18-7 arachidonic acid methyl ester 
• 1191-85-1 eicosa-5,8,11,14-tetraynoic acid 
• 124-38-9 carbon dioxide 
• 95285-77-1 ethyl arachidonate 
• 13553-09-8 (3Z,6Z)-1-oxo-dodecadienal 
• 17814-85-6 (4-carboxybutyl)triphenylphosphonium bromide 
• 506-32-1 all cis 5,8,11,14-eicosatetraenoic acid 
• 94421-68-8 anandamide 
• 65914-84-3 1-stearoyl-2-arachidonoyl-sn-glycerol 
• 21290-17-5 Peroxyarachidonsaeure 
• 53847-30-6 2-arachidonoyl glycerol 
• 3380-34-5 triclosan 
• 946524-40-9 N-(2-hydroxyethyl-1,1,2,2-⁽²⁾H₄)-5Z,8Z,11Z,14Z-eicosatetraenamide 
• 1116491-55-4 N-(2-iodoethyl)arachidonylamide 

Downstream Products

• 2566-89-4 methyl arachidonate 
• 95285-77-1 ethyl arachidonate 
• 54886-50-9 (S)-11-hydroxy-eicosa-5,8,12,14-tetraenoic acid 
• 146797-82-2 1-O-hexadecyl-2-thioarachidonyl-2-deoxy-sn-glycero-3-phosphocholine 
• 69371-38-6 15-HPETE 
• 54397-85-2 thromboxane B₂ 
• 363-24-6 dinoprostone 
• 54397-83-0 12-hydroxyeicosatetraenoic acid 
• 79495-85-5 (5Z,7E,11Z,14Z)-(R)-9-Hydroxy-icosa-5,7,11,14-tetraenoic acid 
• 107656-13-3 9S-hydroxyeicosatetraenoic acid 
• 604-34-2 cholesteryl 5,8,11,14-eicosatetraenoate 
• 110-94-1 1,5-pentanedioic acid 
• 110-15-6 succinic acid 
• 64-18-6 formic acid 

Relevant articles and documents

Liposomal Delivery of Diacylglycerol Lipase-Beta Inhibitors to Macrophages Dramatically Enhances Selectivity and Efficacy in Vivo

Diacylglycerol lipase-beta (DAGLβ) hydrolyzes arachidonic acid (AA)-containing diacylglycerols to produce bioactive lipids including endocannabinoids and AA-derived eicosanoids involved in regulation of inflammatory signaling. Previously, we demonstrated that DAGLβ inactivation using the triazole urea inhibitor KT109 blocked macrophage inflammatory signaling and reversed allodynic responses of mice in inflammatory and neuropathic pain models. Here, we tested whether we could exploit the phagocytic capacity of macrophages to localize delivery of DAGLβ inhibitors to these cells in vivo using liposome encapsulated KT109. We used DAGLβ-tailored activity-based probes and chemical proteomic methods to measure potency and selectivity of liposomal KT109 in macrophages and tissues from treated mice. Surprisingly, delivery of ～5 μg of liposomal KT109 was sufficient to achieve ～80% inactivation of DAGLβ in macrophages with no apparent activity in other tissues in vivo. Our macrophage-targeted delivery resulted in a >100-fold enhancement in antinociceptive potency compared with free compound in a mouse inflammatory pain model. Our studies describe a novel anti-inflammatory strategy that is achieved by targeted in vivo delivery of DAGLβ inhibitors to macrophages.

Stable isotope liquid chromatography-tandem mass spectrometry assay for fatty acid amide hydrolase activity

Fatty acid amide hydrolase (FAAH) is the main enzyme responsible for the hydrolysis of the endocannabinoid anandamide (arachidonoyl ethanolamide, AEA) to arachidonic acid (AA) and ethanolamine (EA). Published FAAH activity assays mostly employ radiolabeled anandamide or synthetic fluorogenic substrates. We report a stable isotope liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for specific, sensitive, and high-throughput capable FAAH activity measurements. The assay uses AEA labeled with deuterium on the EA moiety (d4-AEA) as substrate and measures the specific reaction product tetradeutero-EA (d4-EA) and the internal standard 13C2-EA. Selected reaction monitoring of m/z 66 → m/z 48 (d4-EA) and m/z 64 → m/z 46 (13C2-EA) in the positive electrospray ionization mode after liquid chromatographic separation on a HILIC (hydrophilic interaction liquid chromatography) column is performed. The assay was developed and thoroughly validated using recombinant human FAAH (rhFAAH) and then was applied to human blood and dog liver samples. rhFAAH-catalyzed d4-AEA hydrolysis obeyed Michaelis-Menten kinetics (KM = 12.3 μM, Vmax = 27.6 nmol/min mg). Oleoyl oxazolopyridine (oloxa) was a potent, partial noncompetitive inhibitor of rhFAAH (IC50 = 24.3 nM). Substrate specificity of other fatty acid ethanolamides decreased with decreasing length, number of double bonds, and lipophilicity of the fatty acid skeleton. In human whole blood, we detected FAAH activity that was inhibited by oloxa.

Pig Liver Esterases Hydrolyze Endocannabinoids and Promote Inflammatory Response

Endocannabinoids are endogenous ligands of cannabinoid receptors and activation of these receptors has strong physiological and pathological significance. Structurally, endocannabinoids are esters (e.g., 2-arachidonoylglycerol, 2-AG) or amides (e.g., N-arachidonoylethanolamine, AEA). Hydrolysis of these compounds yields arachidonic acid (AA), a major precursor of proinflammatory mediators such as prostaglandin E2. Carboxylesterases are known to hydrolyze esters and amides with high efficiency. CES1, a human carboxylesterase, has been shown to hydrolyze 2-AG, and shares a high sequence identity with pig carboxylesterases: PLE1 and PLE6 (pig liver esterase). The present study was designed to test the hypothesis that PLE1 and PLE6 hydrolyze endocannabinoids and promote inflammatory response. Consistent with the hypothesis, purified PLE1 and PLE6 efficaciously hydrolyzed 2-AG and AEA. PLE6 was 40-fold and 3-fold as active as PLE1 towards 2-AG and AEA, respectively. In addition, both PLE1 and PLE6 were highly sensitive to bis(4-nitrophenyl) phosphate (BNPP), an aryl phosphodiester known to predominately inhibit carboxylesterases. Based on the study with BNPP, PLEs contributed to the hydrolysis of 2-AG by 53.4 to 88.4% among various organs and cells. Critically, exogenous addition or transfection of PLE6 increased the expression and secretion of proinflammatory cytokines in response to the immunostimulant lipopolysaccharide (LPS). This increase was recapitulated in cocultured alveolar macrophages and PLE6 transfected cells in transwells. Finally, BNPP reduced inflammation trigged by LPS accompanied by reduced formation of AA and proinflammatory mediators. These findings define an innovative connection: PLE-endocannabinoid-inflammation. This mechanistic connection signifies critical roles of carboxylesterases in pathophysiological processes related to the metabolism of endocannabinoids.

Synthesis of 14,15-EET from Arachidonic Acid Using Urea-Hydrogen Peroxide as the Oxidant

14,15- Epoxyeicosatrienoic acid (14,15-EET) is an endogenous bioactive lipid with pharmacological benefits in multiple cardiovascular diseases. We describe here a practical synthesis of 14,15-EET from arachidonic acid using urea-hydrogen peroxide (UHP) as the oxidant.