Gorlic acid

MONOENOIC FATTY ACIDS

In his classic studies on fatty acids from pork fat, Chevreul (1823) recognized the nature of oleic acid but it was not prepared in pure condition for  a long time. Its structure was not definitively elucidated by a series of complex chemical reactions until later (Baruch J, Ber 1894, 27, 172). Much simpler proof of the now accepted structure of oleic acid was given by means of oxidation techniques (Edmed FG, J Chem Soc 1898, 73, 627). The  ozonisation method for the determination of the position of the unsaturated linkage was used for the first time in lipidology in 1903 (Molinari E, Annuario della Soc Chimica di Milano 1903, 9, 507). Oleic acid synthesis was realized in 1934 (Noller CR et al., J Am Chem Soc 1934, 56, 1563).

Mono-unsaturated normal fatty acids are widespread in the living world where they occur mostly as the cis-isomer.  Over a hundred naturally occurring monoene fatty acids have been identified. They have the general structure:

CH₃(CH₂)_xCH=CH(CH₂)_yCOOH

The most frequently they have an even number of carbon atoms and the unique double bond may be in a number of different positions.
 The double bond can exist in two stereoisomeric forms : 

• the cis (or Z) configuration
  

• the trans (or E) configuration

CIS-MONOENOIC FATTY ACIDS

The commonest cis-monoenes are of the n-9 series, as oleic acid from olive oil (cis-9-octadecenoic acid) and from quite all seed oils. 
Some important monoenoic acids are found below:

• Oleic acid is probably the most common fatty acid (olive oil has a high content of this acid: about 60-70%, but it is also found in a large range of nuts). The major sources for human food are palm, rapeseed, soybean, butter, lard and tallow.

While this common fatty acid is mainly found acylated in glycerides, it may be found sometimes as ethyl esters in organs of animal treated with ethanol (Hungund BL et al., J Chem Pharmacol 1988, 37, 3001) and may serve as markers of ethanol intake. (Laposata M, Prog Lipid Res 1998, 37, 307).
The first synthesis of oleic acid appeared in the literature in 1934 (Noller CR et al., J Am Chem Soc 1934, 56, 1563).
Ethyl oleate was identified as a primer pheromone in honey bees in causing a delayed onset of foraging in younger individuals (Leoncini I et al., PNAS 2004, 101, 17559).

• Myristoleic acid is found in most animal depot fats from marine or terrestrial origin. It represents a major component of seed oil from Myristicaceae, some plant species containing up to 30 per cent of this fatty acid in addition to more important amounts of myristic acid. An isomeric form of myristoleic acid was discovered in dolphin and whale head oils (Tsujimoto M, Chem Umschau 1925, 32, 202) and was proved to be the 5-tetradecenoic acid. This uncommon (n-9) fatty acid was more recently described in the retina, acylating an NH₂ terminus  of a protein (recoverin) related to signal transduction in photoreceptors (Dizhoor AM et al., J Biol Chem 1992, 267, 16033). Furthermore, more recently, the presence of this fatty acid in plasma was shown to be of diagnostic value in patients with defects of long-chain fatty acid oxidation (Onkenhout W et al., Clin Chem 1995, 41, 1467).  
  
• Palmitoleic acid is found mainly in animal fats, particularly in fish and marine mammals. This acid was first noticed in 1854 by Hofstädter PG (Ann 1854, 91, 177) in sperm whale oil and named physetoleic acid. Its exact molecular composition (C₁₆H₃₀O₂) was proposed in 1906 by Bull H (Ber 1906, 39, 3570) at the time when its actual name was given by Lewkowitsch. Its structure was established in 1925 (Armstrong EF et al., J Soc Chem Ind 1925, 44, 180T). It has been determined to be abundant in the Asclepediaceae Asclepis syriaca seed oil (10%) (Chisholm MJ et al., Can J Chem 1960, 38, 2500), in the Australian Macademia ternifolia seed oil (20%) (Bridge RE et al., J Chem Soc 1950, 2396), and in the Connaraceae Roureopsis obliquifoliata (32%) seed oil (Spencer GF et al., JAOCS 1978, 55, 689). Later, it was  shown to characterized the seeds of all plants of the Proteaceae family (Badami RC et al., Prog Lipid Res 1981, 19, 119). The berry oil of Hippophae rhamnoides (Sea buckthorn) is known to be rich in palmitoleic acid (16-22%). These plants have potential as sustainable feedstocks for producing industrially important octene via metathesis chemistry. 1-Octene is a high-demand feedstock with a global consumption of over half a million tons per year that is primarily used as a comonomer in the expanding production of linear low density polyethylene. Unfortunately, their low yields and poor agronomic properties preclude their commercial use. Metabolic engineering has been done to achieve high levels of n-7 FA accumulation in Arabidopsis (Arabidopsis thaliana) (Nguyen HT et al., Plant Physiol 2010, 154, 1897).

  Palmitoleic acid was demonstrated to be an adipose tissue-derived hormone (a lipokine) that strongly stimulates in mice muscle insulin action and suppresses hepatosteatosis. Adipose tissue would be able to use lipokines to communicate with distant organs and regulate systemic metabolic homeostasis (Cao H et al., Cell 2008, 134, 933). The amount of palmitoleic acid in serum cholesterol ester reflects the hepatic pool of carbon flux from carbohydrates to fatty acids (Lands W et al., Am J Clin Nutr 1995, 61, 721). Furthermore, as a product of endogenous lipogenesis, palmitoleic acid is reported to correlate with indexes of adiposity and insulin concentrations (Kunesova M et al., Lipids 2002, 37, 27). On the other hand, palmitoleic acid has been used as a biomarker to trace dairy products intake in human (Mozaffarian D et al., Am J Clin Nutr 2013, 97, 854).

   

• Petroselinic acid is present as a major component (from 15 to 60%) in many species of Umbelliferae (parsley or coriander oilseeds) and Araliaceae (Hedera helix). Its presence was first noted in 1909 in parsley seed oil (Vongerichten et al., Ber deutsch chem Ges 1909, 42, 1638) and in the seeds of ivy (Hedera) (Steger A et al., Rec Trav Chim 1928, 47, 471) and its exact structure was determined. Within the Umbelliferae, it was shown that the genus Thapsia should be regarded as a useful source of petroselinic acid, which represents an important oleochemical material for the food, cosmetics, chemistry and pharmaceutical industries (Avato P et al., Lipids 2001, 36, 845). Petroselinic acid was also shown to be an important constituent of Geranium sanguineum (Geraniaceae) seed oil (about 48%) (Tsevegsuren N et al., Lipids 2004, 39, 571) and of sweet cicely (Myrrhis odorata, Umbelliferae) (82%).
  
• Vaccenic acid (from Vacca : cow), named also asclepic acid, was discovered in 1928 (Bertram SH, Biochem Z 1928, 197, 433) in animal fats and butter. 
  
• Gadoleic acid was first noted in cod liver oil (Bull H, Ber 1906, 39, 3570), present in marine fish, it originates from dietary crustacea. Its structure was given in 1933 (Takano M J, Soc Chem Ind Japon 1933, 36, 1317). A shorter fatty acid of the n-11 family, 16:1 n-11, is abundant in psychrophile bacteria, such as Bacillus (Kaneda T, Biochem Biophys Res Commun 1971, 43, 298) and thermophile bacteria, such as Chthonomonas (Vyssotski M et al., Lipids 2011, 46, 1155).
  
• Nervonic acid, with 24 carbon atoms, was first believed to be characteristic of fats of Elasmobranch fish (first name: selacholeic acid) where it was discovered (Tsujimoto M, J Soc Chem Ind Japon 1927, 30, 868). In the same year, Klenk E (Z physiol Chem 1927, 166, 287) isolated this fatty acid from cerebrosides of brain tissue, and established its structure. This acid is also present in a Cruciferae (Lunaria annua) in high amounts (22-25%) where it can be suitable (together with erucic acid) for production of high-temperature lubricants and engineering nylons. 
  
• Erucic acid, with 22 carbon atoms,  is found in high amounts (up to 50%) in seed oils of the Cruciferae such as Nasturtium, rape, mustard, Lunaria (38-48%) and of the Tropaeolaceae. Other species have been proposed as sources of erucic acid for nonfood applications, crambe (Crambe abyssinica)(about 60%) and meadowfoam (Limnanthes alba) (about 15%) but there has been no sustained production of these plants. This acid is used in the manufacture of polyethylene film. Tests on animals have shown that ingesting oils containing erucic acid over time can lead to a heart condition called myocardial lipidosis. This is temporary and reversible. Other potential effects observed in animals – including changes in the weight of the liver, kidney and skeletal muscle – occur at slightly higher doses. EFSA’s Panel on Contaminants in the Food Chain established a tolerable daily intake of 7 milligrams per kilogram of body weight (mg/kg bw) per day. For most consumers, especially for toddlers (1-2 years old) and other children (3-10), the main contributors to erucic acid exposure in the diet are pastries, cakes and biscuits. For infants (0-12 months), infant formulae is the main source.Erucic acid is not a safety concern for most consumers as average exposure is less than half the safe level. But it may be a long-term health risk for children up to 10 years of age who consume high amounts of foods containing this substance.
  

N-3 monoenes : An unusual isoform, the lauroleic acid (9-dodecenoic acid, 12:1 n-3) has been described as a natural metabolite of lauric acid (12:0) in rat hepatocytes (Legrand P et al., Lipids 2002, 37, 569)

N-7 monoenes : The 5-dodecenoic acid (denticetic acid, 12:1 n-7) is present in sperm whale oil. This compound was formerly known to be present in milk lipids. 
The rare 21:4 n-7 has been described in some animal species (crab, sponge, protist), but it was found in high amount (about 9 % of the total fatty acids) in a opisthobranch mollusc, Scaphander lignarius (Vasskog T et al., Mar Drugs 2012, 10, 2676). That fatty acid was shown to be cytotoxic against human cancer cell lines normal lung fibroblasts, more than EPA and arachidonic acid.

N-8 monoenes : An isomer (12:1 n-8, linderic acid) has been found as the major fatty acid (47%) in the seed oil of a Lauraceae, Lindera umbellata (Hopkins CY et al., Lipids 1961, 1, 118). This fatty acid is not known to occur in any other plant family.

N-10 monoenes : Sapienic acid (16:1 n-10), a 16-carbon fatty acid with a single cis double bond at the sixth carbon from the carboxyl end, is the most abundant fatty acid in human wax sebum, and among hair-bearing animals is restricted to humans (Nicolaides N, Science 1974, 186, 19). Sapienic acid has been also identified in in human hair and nail samples beside 18:1n-10 (Destaillats F et al., J Chromatogr A 2011, 1218, 9384). Thus this fatty acid is truly unique to sebum, hair and nail and is not found anywhere else in the human body.
Notably, this fatty acid has been implicated in the pathogenesis of acne (Downing DT et al., J Am Acad Dermatol 1986, 14, 221) but was shown to be effective against gram-positive bacteria in human skin sebum (Wille JJ et al.., Skin Pharmacol Physiol 2003, 16, 176). Further works characterized its biosynthesis by a D-6 desaturase acting on palmitic acid  (Ge L et al., J Invest Dermatol 2003, 120, 707). 

N-15 fatty acids : An unusual 20 carbon fatty acid (20:1 n-15) is found in high concentration (about 60%) in seeds of Limnanthes alba (meadowfoam), an herbaceous winter annual plant native to the pacific Northwest area of the United States. 

No fatty acid exists naturally with the double bond close to the terminal methyl group, only one is chemically synthesized from ricinoleic acid, the undecylenic acid (11:1 n-10).

TRANS-MONOENOIC FATTY ACIDS

One geometrical and several positional isomers of oleic acid exist with a trans double bond. Among the naturally occurring  trans isomers, the double bond is in the (n-13), (n-12), (n-9) or (n-7) position.
Vegetable oils and fats are almost trans free, if not warmed at high temperature in the presence of active components. In contrast, trans fatty acids occur in most animal fats especially in butter and ruminant fats. 

Trans-fatty acids are also formed under the action of thiyl radicals.

Saturated fatty acids

trans-Fatty acid

cis-Fatty acid

An unusual trans fatty acid, t3-hexadecenoic acid (trans-16:1 n-13), occurs in eukaryotic photosynthetic membranes (mainly in phosphatidylglycerol) from higher plants and green algae. As this fatty acid is absent from etiolated tissue, it has been inferred that it has a specific role associated with the light reactions of photosynthesis (Gounaris K et al., Biochem J 1986, 237, 313).

RING CONTAINING FATTY ACIDS

1 – Cyclopropane, cyclopropene, cyclopentyl,cyclopentenyl, cyclohexyl, and cyclohexenyl acids

Cyclopropane, cyclopropene

Among cyclopropane acids, lactobacillic acid (11,12-methylene-octadecanoic acid) is found mainly in a gram-negative bacteria, Lactobacillus arabinosus, where it was discovered in 1951 (Hofman K et al., J Biol Chem 1951, 195, 473). but also in protozoa and in the seed oil of Byrsocarpus coccineus (Connaraceae) (Spencer GF et al., Lipids 1979, 14, 72). Its ring has some properties of a double bond and it may be disrupted by acids or halogens. In bacteria, lactobacillic acid is never accompanied by cyclopropene acids.

Cyclopropane fatty acids (mainly lactobacillic acid) were detected for the first time in milk (about 0.1% of milk fat) and they were present only in milk samples from cows fed with forages containing maize silage (Marseglia A et al., Food Chem 2013, 140, 711). Their determination can be proposed as a quality parameter of milk or feed.
The seeds of Litchi chinensis (Sapindaceae) from Reunion Island were shown to contain unusual amounts (35-48%) of an isomer of lactobacillic acid : cis-9,10-methylene-octadecanoic acid (Gontier E et al., Biochem Soc Trans 2000, 28, 578). That cyclopropane fatty acid is  also present in longan (Euphoria longana) seed oil (Grondin I et al., Oléagineux Corps gras Lipides 1997, 4, 459). Furthermore, it was shown that this fatty acid was preferentially located at the sn-2 position of the triglyceride molecules.
Another cyclopropane fatty acid (9,10-methylene-hexadecanoic acid) was recently shown to be present in phospholipids of heart and liver mitochondria (Sakurada K et al., Biochim Biophys Acta 1999, 1437, 214). Its amount in bovine heart (about 4% of all fatty acids) is much greater than that in other tissues (less than 0.3%). The origin and the physiological role of these compounds remain unclear. Cyclopropane fatty acids have been also identified in human adipose tissue and serum (Sledzinski T et al., Lipids 2013, 48, 839). These compounds are stored in triacylglycerols but their origin remains unknown.

A novel brominated cyclopropyl fatty acid, majusculoic acid, with a 16-carbon chain has been reported in a cyanobacteria Lyngbya majuscula and was shown to exhibit antifungal activity against Candida albicans (MacMillan JB et al., J Nat Prod 2005, 68, 604).

Two unsaturated cyclopropyl C28 fatty acids (named amphimic acids), 10,11-methylene-28:2(5Z,9E) and 10,11-methylene-28:3(5Z,9E,21Z) were isolated from an Australian sponge Amphimedon sp., and were shown to be DNA topoisomerase inhibitors (Nemoto T et al., Tetrahedron Lett, 1997, 38, 5667; Tetrahedron, 1997, 53, 16699).

Cyclopropene acids are found in Malvales seed oils (Sterculiaceae, Gnetaceae, Bombacaceae, Tiliaceae, Malvalaceae and Sapindaceae) and Baobab, Kapok and Mowrah seed oils which are used as human food in Madagascar. They can reduce the commercial value of cotton (Malvales, Gossypium) seed oil in interfering with animal fatty acid metabolism (desaturation of stearic acid). Such toxic acids are deactivated or removed by normal industrial treatments. The biological effects of these molecules have been reviewed by Andrianaivo-Rafehivola AA et al. (Oleagineux 1994, 49, 177).
Compounds containing cyclopropenoid ring are associated with several biological properties, such a : insecticide, antifungal, antibiotic, antiviral, hormonal, carcinogenic or antitumoral activities and enzyme inhibitor (Salaun J, Top Curr Chem 2000, 207,1).
The 9,10-methylene octadec-9-enoic acid was discovered by Nunn (1952) in Sterculia foetida oil. It was named sterculic acid by Schlenk et al. (J Am Chem Soc 1952,72, 500). An homologue molecule, 8,9-methylene heptadec-8-enoic acid, was discovered in 1957 by Mac Farlane (Nature 1957, 179, 830) in Malva verticillata seed oil and named malvalic acid. Cotton oil (Gossypium hirsutum) was the first oil, used for human consumption, where cyclopropenic acids were shown to be present (Coleman EC et al. 1972) by the Halphen test (J Pharm 1897, 390). Sterculic acid was shown to be an inhibitor of the D9-desaturase which converts stearic acid into oleic acid, altering membrane permeability and inhibiting cellular reproduction (Dewick PM, Medicinal natural products, J Wiley and Sons, NY, 2001).
Both cyclopropenic acids are present in Malvales in various proportions. In Sterculiaceae, malvalic acid is present in the range 3-26% and sterculic acid in the range 5-54%, in Malvaceae O.5-5% and 0.3-7%, in Gnetaceae 13-39% and 13-28%, and in Bombacaceae 2-20% and 1-46%, respectively. 

The Sterculia striata seeds, known as "chicha" nut in Brazil, are consumed by man and their oil was shown to contain about 4% of malvalic acid and 11% of sterculic acid (Aued-Pimentel S et al., J Chromatogr A 2004, 1054, 235). These levels may thus compromised the use of these nuts due to possible health implications caused by cyclopropenoid acid ingestion.
A review summarized the occurrence of cyclopropene acids in numerous plant families (Christie WW, in "Topics in Lipid chemistry", vol 1, pp1-50, Logos Press Ltd 1970). This review may be completed with that of Vickery JR (JAOCS 1980, 57, 87).

Cyclobutane acids (ladderanes)

Fatty acids with cyclobutane rings were discovered as constituents of membrane lipids in anaerobic ammonium-oxidizing (anammox) bacteria (Candidatus spp, order of the Planctomycetes) (Damsté S et al., Nature 2002, 419, 708). These fatty acids contain up to five linearly fused cyclobutane moieties, sometimes mixed with one or two cyclohexane rings (Damsté S et al., FEBS J 2005, 272, 4270). A typical example is pentacycloanammoxic acid which is composed of 5 fused cyclobutane units.

Ladderane fatty acids

Such "ladderane" structures are unprecedented in nature and occur in bacterial membranes as free fatty acids, fatty alcohols, alkyl glycerol mono- or di-ethers, phosphocholine diether and phosphocholine ester/ether and phosphoethanolamine diether and phosphoethanolamine ester/ether (Boumann HA et al., FEMS Microbiol Lett 2006, 258, 297). They are supposed to protect the cell from the toxic anammox intermediates located in specialized organelles (anammoxosomes). These lipids seem to be limited to these bacteria which were shown to play an important role in the nitrogen cycle in the ocean (Kuypers M et al., Nature 2003, 422, 608). Therefore, they are considered to be the unique biomarkers for the process of anaerobic ammonium oxidation. They were detected in suspended particulate matter obtained from various water depths in the Arabian Sea (Jaeschke A., Limnol Oceanogr 2007, 52, 780) and in sediments (Hopmans EC et al., Rapid Comm Mass Spectrom 2006, 20, 2099).

Cyclopentyl and Cyclopentenyl acids

Cyclization and rearrangement mechanisms that are involved in the formation of cyclic fatty acids and their further transformation into bicyclic fatty acid monomers during the frying process have been determined. Insights into cyclization and rearrangement mechanisms that may be involved in the formation of these cyclic fatty acids have been reported by Destaillats F et al. (Destaillats F et al. Eur J Lipid Sci Technol 2005, 107, 767).
Naphthenic acids are complex mixtures of archaeal isoprenoid fatty acids formed by a link between two diacids with several cyclopentane rings (Lutnaes BF et al., Org Biomol Chem 2006, 4, 616). The structures of C80, C81 and C82 isoprenoid tetraacids have been finely described (Lutnaes BF et al., Org Biomol Chem 2007, 5, 1873). These tetra-acids (Arn acids) are present in crude oil and their calcium salts can cause serious problems during the industrial process (corrosion, formation of emulsion, clogging by the salts). The family members differ by their number of cyclopentane rings and by their molecular weight (400-1300 g/mol). The most abundant Arn acid has 80 carbon atoms and 6 cyclopentane rings.

Cyclohexyl and cyclohexenyl acids

Cyclohexyl fatty acids were first found in butter (Shogt JC et al., 1965, 6, 466) and then in sheep fat (Hansen RP et al., J Sci Food Agric 1967, 18, 225) and rumen bacteria (Hansen RP, Chem Ind 1967, 39). The most common cyclohexyl acids are 11-cyclohexyl-C11 and 13-cyclohexyl-C13 (see below).

The content of w-cyclohexyltridecanoic acid varied from 0.0% to 0.15% of milk fat, and it was higher in milk samples from cows fed with diets richer in cereal meals (Marseglia A et al., Food Chem 2013, 140, 711).
While these w-cyclohexyl acids were detected in a mesophile bacteria Curtobacterium pusillum (Kawagushi A et al., J Biochem 1986, 99, 1735), they are curiously more abundant in thermophile bacteria. Thus, they are, in equal amounts, the major components (about 65%) of the fatty acids in Bacillus acidocaldarius (= Alicyclobacillus), a gram-positive rod-shaped prokaryote found in acid hot springs up to 65°C (De Rosa M et al., Chem Commm 1971, 1334). They were also found in ten strains of acido-thermophilic bacteria isolated from different Japanese hot springs (Oshima M et al., J Biol Chem 1975, 250, 6963). These fatty acids were found in the esterified form in glyceride type lipids, amounted to 74 to 93% of the total fatty acids in the bacteria, and were shown to be formed from glucose and shikimic acid. More recently, cyclohexyl undecanoic acid was shown to be the major cellular fatty acid in Propionibacterium cyclohexanicum, a new acid-tolerant bacteria isolated from spoiled orange juice (Kusano K et al., Int J Syst Bacteriol 1997, 47, 825).
Some C17 and C19 cyclohexyl alkanoic acids have been identified in acidothermophilic bacteria in hot springs. Furthermore, a series of alkyl cyclohexanes and cyclohexyl alkanoic acids were detected in lacustrine saline petroleum samples from Brazil (Nascimento LR et al., Org Geochem 1999, 30, 1175). The origin of these compounds is still unknown, but a correlation was made with the presence of Alicyclobacillus in the formation water and oil samples (Rodrigues DC et al., Org Geochem 2005, 36, 1443).

During heating of vegetal oils, linolenic acid gives rise to dienoic acids containing a cyclohexenyl or a cyclopentenyl ring. Similarly, deodorization of fish oil rich in eicosapentaenoic and hexaenoic acids generates about 15 cyclohexyl and cyclopentyl fatty acids with a 20 and 22 carbon chain, respectively (Berdeaux O et al., J Chromatogr A 2007, 1138, 216). One of the most abundant cyclic monomers  formed from EPA (8-(2′-hexylcyclohexyl) octanoic acid) is shown below.

8-(2′-hexylcyclohexyl) octanoic acid

A more complex fatty acid containing a highly functionalized cyclohexanone has been isolated from the endophytic fungi Pestalotiopsis spp and Monochaetia sp living in the thalli of lichens (Li JY et al., Phytochemistry 2001, 56, 463). The compound, named ambuic acid, contains a hexa-substituted cyclohexanone moiety, as it was found in a tetracycline antibiotic.

Ambuic acid

Ambuic acid has displayed antifungic activity against human pathogenic fungi. Several secondary metabolites of ambuic acid have been described in the same fungus (Pestalotiopsis sp) (Ding G et al., J Nat Prod 2009, 72, 182). Ambuic acid and one of its metabolites displayed anti-microbial activity against the Gram-positive bacterium Staphylococcus aureus.

The furan acid described initially was the 9,12-epoxy-octadeca-9,11-dienoic acid (R1, R2 = H, m = 7 and n = 5 in the general formula above).

A common nomenclature describing these fatty acids (as F1, F2,…) is used. This naming originated from elution order in gas chromatography. 
The most frequent compound is known as F6 (12,15-epoxy-13,14-dimethyleicosa-12,14-dienoic acid) while, later, two series of propyl- and pentyl-substituted F-acids in the 5-position of the furan ring was described in fish, crayfish, soft coral and various algae and terrestrial plants. Their presence was more recently detected in mammals including man (Puchta V et al., Liebigs Ann Chem 1988, 25). In man, furan fatty acids were located in phospholipid fractions.
In fish, furan fatty acids are found in liver cholesterol esters and in testis triglycerides, but are also present in phospholipids. In 1977, height furan fatty acids were listed in several organs of 20 fresh water fish species (Glass RL et al., Lipids 1977, 12, 828). Forty furan fatty acids were identified in a marine fish oil, two propyl-substituted molecules being reported for the first time (Wahl HG et al., J High Resol Chromatogr 1994, 17, 308).
As a furan fatty acid (10,13-epoxy-11-methyloctadeca-10, 12-dienoic acid) was detected in the cellular lipids of several marine bacteria (Shirasaka N et al., Biochim Biophys Acta 1995, 1258, 225), the authors propose that those detected in marine fish are derived from marine plants and/or intestinal bacteria of fishes.

10,13-Epoxy-11-methyloctadeca-10, 12-dienoic acid

g/g dry w.), lemon (30 mg/g dry w.), strawberry, orange, potato (2-5 mg/g dry w.) and even in mushroom (160 mg/g dry w.) (Hannemann K et al., Lipids 1989, 24, 296). By far the richest source of furan fatty acids in food is fish.  Concentrations of up to 4 g/100 g oil were reported in the literature (Vetter W et al., J. AOCS 2012, 89, 1501). Frequently, the furan acid concentrations were in the range 0.1-0.9 g/100 g oil, with a clear dominance of dimethylated derivatives. Lower concentrations have been reported in other fatty sources : butter (48 mg/100 g), soybean oil (42 mg/100 g), wheat germ oil (22 mg/100 g).  

It appears possible that these furan compounds may serve as antioxidants in biological systems through their ability to scavenge free radicals (Okada Y et al., Biol Pharm Bull 1996, 19, 1607). The radical scavenging Furan acids are able to eliminate radicals before their concentrations are exponentially increasing by means of a radical chain reaction. The strong capability of these compounds to serve as radical scavengers suggests that plants and algae can use these compounds to defend against the deleterious effect of UV radiation (Spiteller G, Lipids 2005, 40, 755). A review has focused mainly on the functions and roles of furan acids in plants (Mawlong I et al., Phytochem Rev 2016, 15, 121). It is recalled that In plants, they are bound to phospholipids by substituting polyunsaturated fatty acids and function as free radical scavengers suggesting their role in defense against oxidative stress.

 It was hypothesized that the radical-scavenging ability of furan fatty acids could contribute to the protective properties of fish diets from heart disease (Spiteller G, Lipids 2005, 40, 755). A first in vivo demonstration has been given using furan fatty acids isolated from a mussel Perna canaliculus, native to the New Zealand coast (Wakimoto T. et al., PNAS 2011, 108, 17533). These fatty acids exhibited in a rat model of adjuvant-induced arthritis a more potent anti-inflammatory activity than that of EPA. These anti-inflammatory effects corroborate the observation of a lower incidence of arthritis in coastal Maoris, eating these mussels, compared with its prevalence in European or inland Maori people. 

A rapid method for the preparation of C18 furanoid fatty aster from methyl ricinoleate involving dry-column chromatography was described (Lie Ken Jie MSF et al., JAOCS 1981, p. 705).
A method for the quantitative determination of furan acids in food has been reported (Vetter W et al., JAOCS 2012, 89, 1501). After extraction, transesterification and silver ion chromatography, the furan acids are anayzed by GC/EI-MS.

Epoxy acids

Epoxy acids are present in a number of seed oils (in triacylglycerols) and in plant cutin and suberin. The natural species are all C18 compounds, saturated on unsaturated. On prolonged storage, they can be formed as hydroxy derivatives. For example, 9,10-epoxystearic and 9,10-epoxyoctadec-12-enoic (coronaric acid) acids are found in sunflower seeds (Chrysanthemum). The seed oil of Bernardia pulchella (Euphorbiaceae) contains 91% of coronaric acid (Spitzer V et al., JAOCS, 1996, 73, 1733). These fatty acids are commonly used to make paints and coatings.

These two epoxy acids are commonly present in cutin and suberin up to an amount of 34% of the lipid content. 
Vernonia and Stokesia species are among plants identified as containing epoxy fatty acids at high percentages in their seed oils. Works are in progress in Africa to improve crops of these plants.
Vernolic acid is the best known epoxy acid from natural sources. This isomer of coronaric acid is 12,13-epoxy-9-octadecenoic acid was characterized as an epoxy oleic acid (Gunstone FD, J Chem Soc 1954, 1611) and was shown to be abundant in seed oils of the Compositae Vernonia sp as well as Euphorbia lagascae (from 60 up to 75%). 
Small quantities (about 2.5%) of 9,10-epoxy-18:0, vernolic acid and coronaric acid were found in peanut (Arachis hypogaea) germplasm (Hammond EG et al., JAOCS, 1997, 74, 1235). Vernolic acid was also shown to be present (7%) in the seed oil of Geranium sanguineum (Geraniaceae) (Tsevegsuren N et al. Lipids 2004, 39, 571).
A C20 homologue of vernolic acid has been found in Alchornea cordifolia (Euphorbiaceae) seed oil (Kleiman R et al., Lipids 1977, 12, 610). This new fatty acid, cis-14,15-epoxy-cis-11-eicosenoic acid has been named as alchornic acid.
Epoxide groups are also present in bacterial lipids.

Cyclic fatty acid endoperoxides

It is well known that cyclic peroxide products may be produced during the autoxidation of polyunsaturated fatty acids. In contrast with these labile compounds, several cyclic peroxides have been described in lipid extracts from marine sponges (Faulkner DJ, J Nat Prod 1997, 14, 259). Almost all these molecules are assumed to derive from the polyketide pathway and derived from a common backbone : CH₃-(CO-CH₂)_n-COOH
The first of these compounds to be reported was plakortin, a six membered ring cycloperoxide found in 1978 by Faulkner’s group in the marine sponge Plakortis halicondrioides (Higgs M D et al., J Org Chem 1978, 43, 3454).

 Subsequently, a series of related bioactive metabolites have been isolated. They include plakinic acids (Davidson, B. S. J. Org. Chem., 1991, 56, 6722), the strongly antifungal peroxyplakoric acids (Kobayashi M et al., Pharm Bull, 1993, 41, 1324) and the recently reported activators of cardiac Ca ATPase plakortones A-D (Patti AD et al., Tetrahedron 1996, 52, 377).
In 1998, several cyclic peroxide homologues have been described in the same sponge species, either active against cancer cell lines (Harrison B et al., J Nat Prod 1998, 61, 1033), toxic toward Artemia larvae (Braekman JC et al., J Nat Prod 1998, 61, 1038), inhibitor of the protozoan causing leishmaniasis (Compagnone RS et al., Tetrahedron 1998, 54, 3057), or without known biological activity (Fontana A et al., J Nat Prod 1998, 61, 1427). Several metabolites of plakortin with various cytotoxic activities have been also isolated from Plakortis simplex : dihydroplakortin and two dodecanoic derivatives (Cafieri F et al., Tetrahedron 1999, 55, 7045). Later, other related cytotoxic endoperoxides have been isolated from the Okinawan sponge Plakortis lita and named Haterumadioxins (Takada N et al., J Nat Prod 2001, 64, 356) and from Plakortis simplex (Holzwarth M et al., J Nat Prod 2005, 68, 759).

Lipoic acid

This compound was first considered as a microbial growth factor but it was found not only in yeast but also in beef liver from which it was first isolated in pure form (Reed LJ et al., J Am Chem Soc 1953, 75, 1267). This isolation is one of the more spectacular achievements in the purification of natural products, since 30 mg of crystalline lipoic acid was obtained from 10 tons of liver. Lipoic acid was named also thioctic acid or 1,2-dithiolane-3-pentanoic acid. After its absorption, this acid is reduced enzymatically by NADH or DADPH to dihydrolipoic acid (or 6,8-dithiane octanoic acid) in various tissues. A fraction of the total lipoic acid pool is covalently bound to   enzyme molecules through an amide linkage with a lysine residue.

First shown necessary for bacteria, lipoic acid was demonstrated to be a coenzyme in the glycine cleavage system and in the dehydrogenase complex. Now, lipoic acid is considered as an efficient antioxidant since with its reduced form it constitutes a redox couple via modulation of NADH/NAD ratio. Consequently, lipoic acid has gained a special interest as a therapeutic agent (Packer L et al., Free Radic Biol Med 1997, 22, 359). It can scavenge hydroxyl and peroxyl radicals but also chelates transition metals (Fe, Cu…). Packer L. considered that lipoic acid is perhaps the most powerful of all the antioxidants, it may offer an efficient protection against many heart diseases, it is currently used  to relieve  the complications of diabetes (Packer L et al. The antioxidant miracle. John Wiley & Sons 1999).

ACETYLENIC FATTY ACIDS

This class, known also as ethynoic acids, includes fatty acids which contain a triple bond (or more as in polyacetylenes) and eventually one or two double bonds. While many acetylenic fatty acids have been prepared synthetically, only some species are found in natural oils.

MONOACETYLENIC ACIDS

Stearolic acid (9-octadecynoic acid) is present in seeds of Santalaceae.

Tariric acid (6-octadecynoic acid) was first reported in the seed fat of the Simarubiaceae Picramnia tariri (Arnaud A, C R Acad Sci 1892, 114, 79) an later in other Picramnia species. Among them, the seed oil from Picramnia sow, a plant indigenous to Guatemala, has been reported to contain nearly 95% of tariric acid (Steger A et al., Rec Trav Chim 1933, 52, 593).

Santalbic acid (or Ximenynic acid) has been described in the seed fat of Santalum album at high concentration (50%) (Madhuranah MK et al., J Indian Chem Soc 1938, 15, 389) and its structure was later identified (Gunstone FD et al., Chem Ind 1954, 1112).&nbsp

The two acetylenic fatty acids, santalbic acid and stearolic acid, were isolated from the seeds of Exocarpus and Santalum (Morris LJ et al., Chem Ind 1966, 12, 460). This distinctive biochemical feature was discovered in santalwood oil from a small tree or shrub (Santalum spicatum) native to the Western Australia (Hatt HA et al., J Sci Food Agric 1956, 7, 130). Its large fruit contain a hard-shelled seed rich in a drying fixed oil (50-60%). About 30-35% of total fatty acids are represented by santalbic acid and 1% by stearolic acid. When administered to animals these fatty acids were described to inhibit several lipoenzymes (lipoxygenase, prostaglandin synthetase) and modify tissue fatty acid composition (Liu Y et al., Lipids 1997, 32, 965). 

6,9-octadecenynoic acid (6-octadecen-9-ynoic acid) was isolated from nuts of Ongokea klaineana. This compound contains a triple-bond at carbon 9 and a double bond at carbon 6.

Pyrulic acid (t10-heptadecen-8-ynoic acid) was isolated first from seed oil  from a Santalaceae Pyrularia pubera, and recently found in a Olacaceae from southern Brazil, Heisteria silvanii (Spitzer V et al., Lipids 1997, 32, 1189).

Crepenynic acid (9-octadecen-12-ynoic acid) was found in high concentration (60%) in oil extract from seeds of Crepis foetida (Compositae) (Mikolajczak KL et al., J Org Chem 1964, 29, 318). Toxic effects of plants containing this fatty acid have been reported in Australian sheep.

Crepenynic acid

The distribution of crepenynic acid and dehydrocrepenynic acid (9,14-octadecen-12-ynoic acid) (65% of total fatty acids) in triacylglycerols of the aril and cotyledon oils of Afzelia cuanzensis (Caesalpinaceae) was studied by nuclear magnetic resonance spectroscopy (Vlahov G, Phytochemistry, 1996, 42, 621). 
The oil from the seed of Alvardoa amorphoides (Simarubiaceae) was reported to contain about 15% of 17-octadec-6-ynoic acid, the predominant fatty acid of this oil being tariric acid (Pearl MB et al., Lipids 1973, 8, 1284).
Similar acetylenic acids, but with 14 to 18 carbon atoms and one to three hydroxyl groups have been described in the fungus Coriolopsis gallica (basidiomycete) (Zhou ZY et al., J Nat Prod 2008, 71, 223).

Two acetylenic acids with one triple double bond and one double bond were described in a Santalaceae, Nanodes muscosa from Chili. One of them (compound 2) constitutes the first example of an a,w fatty diacid with a conjugated enzyme system from a natural source (El-Jaber N et al., J Nat Prod 2003, 66, 722).

Scleropyric acid was isolated from another Santalaceae, Scleropyrum wallichianum (Suksamrarn A et al., Chem Pharm Bull 2005, 53, 1327). That acetylenic acid exhibited antimycobacterial (MIC : 25 mg/ml) and antiplasmodial  (MIC : 7.2 mg/ml) activities.

Scleropyric acid

An acetylenic fatty acid with ene-yne-ene structure was described in an Olacaceae, Heisteria silvanii (popular name "casca-de-tatu): heisteric acid (Spitzer V et al., Lipids 1997, 32, 1189). It has been tentatively characterized by their mass spectra as cis-7,t11-octadecen-9-ynoic acid and determined to present at a level of about 23% in seed oil

  
A conjugated t,t-diunsaturated acetylenic acid was found as a main component in the seed oil of an ornemental Asteraceae, Tanacetum (Chrysanthemum) corymbosum (Compositae). This fatty acid was shown to be t8, t10-octadecadien-12-ynoic acid (Tsevegsuren N et al., Lipids 1998, 33, 723).

Acetylenic acids were also described in sponges. Several compounds with a branched-chain, an acetylenic moiety in the middle of the molecule and a terminal double bond, and sometimes with a methoxy group were described in a marine sponge Stelletta species (Lee HS et al., J Nat Prod 2003, 66, 566; Zhao Q et al., J Nat Prod 2003, 66, 408).

POLYACETYLENIC   ACIDS

Polyacetylene fatty acids are not commonly found in living organisms. Mycomycin, which is produced by a mold-like Actinomycete and is active against the Bacilli sp of human tuberculosis was discovered in 1947 by Johnson EA et al. (J Bacteriol 1947, 54, 281). This fatty acid has two triple bonds but has also an allenic structure : tridecatetra-3,5,7,8-en-10,12-diynoic acid.
A diynoic acid (13,14-dihydrooropheic acid) has been isolated from an Indonesian plant (Mitrephora celebica, Annonaceae) and was shown to have a potent antimicrobial activity (Zgoda J et al., J Nat Prod 2001, 64, 1348).

Another diynoic acid (octadecen-13-en-9,11-diynoic acid) has been described in Santalum acuminatum and also in Nanodea muscosa (Santalaceae) where its exact structure was elucidated (El-Jaber N et al., J Nat Prod 2003, 66, 722). Several others have been described in Olacaceae : octadeca-13-en-9,11-diynoic acid (exocarpic acid), octadeca-13,17-dien-9,11-diynoic acid, octadeca-17-en-9,11-diynoic acid (isanic acid), and octadeca-9,11-diynoic acid (Badami RC et al., Prog Lipid Res 1981, 19, 119).

Three fatty acids with an allenyldiyne structure, phomallenic acids A-C, have been isolated from the fermentation broth of Phoma sp. Phomallenic acid C had the most potent activity as an inhibitor of bacterial FAS II pathway (Ondeyka JG et al., J Nat prod 2006, 69, 377).

A triynoic acid (oropheic acid) was isolated from leaves of Orophea enneandra (Annonaceae)(Cavin A et al., J Nat Prod 1998, 61, 1497) and of Mitrephora celebica (Zgoda J et al., J Nat Prod 2001, 64, 1348). It displayed a significant activity against the fungus Cladosporium.

A 9-carbon triynoic acid containing a terminal acetylene has been isolated first from the Basidiomycetes Psilocybe sarcocephala (Jones ERH, Proc Chem Soc 1960, 199) but was later found in other fungi of the same group. An amide of that fatty acid with p-aminobenzoic acid has been shown to be present in the fungus Baeospora myosura and to have a selective antibacterial activity (Parish CA et al., J Nat Prod 2004, 67, 1900). Triacetylenic acids, named corticatic acids, have been isolated from the marine sponge Petrosia corticata. One of them is shown below. All are geranylgeranyltransferase type I (from Candida albicans) inhibitors (Nishimura S et al., J Nat Prod 2002, 65, 1353).

Corticatic acid A

Another triynoic acid with 20 carbon atoms, from synthetic origin, is frequently used to experimentally inhibit essential fatty acid metabolism and especially cyclooxygenase and lipoxygenase pathways: 5,8,11,14-eicosatetraynoic acid (ETYA).

A tetraynoic acid (Haliclonyne) was isolated from the marine sponge Haliclona collected at Eilat (Israel) (Chill L et al., J Nat Prod 2000, 63, 523). This highly polyacetylene compound is a C47 oxo-octahydroxy-dientetrayne carboxylic acid.

A review of several polyacetylenic acids in plants and the current state of knowledge of the biochemistry and molecular genetics of polyacetylenic metabolic pathways may be consulted (Minto RE et al., Prog Lipid Res 2008, 47, 233).