Skatole

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Skatole
Skatole structure.svg
Skatole 3d structure.png
Names
Preferred IUPAC name
3-Methyl-1H-indole
Other names
3-Methylindole
4-Methyl-2,3-benzopyrrole
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.001.338 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C9H9N/c1-7-6-10-9-5-3-2-4-8(7)9/h2-6,10H,1H3 Yes check.svgY
    Key: ZFRKQXVRDFCRJG-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C9H9N/c1-7-6-10-9-5-3-2-4-8(7)9/h2-6,10H,1H3
    Key: ZFRKQXVRDFCRJG-UHFFFAOYAZ
  • Cc1c[nH]c2ccccc12
  • c1cccc2c1c(c[nH]2)C
Properties
C9H9N
Molar mass 131.178 g·mol−1
AppearanceWhite crystalline solid
Odor Fecal Matter (In low concentrations it can have a pleasant flowery aroma)
Melting point 93 to 95 °C (199 to 203 °F; 366 to 368 K)
Boiling point 265 °C (509 °F; 538 K)
Insoluble
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Skatole or 3-methylindole is an organic compound belonging to the indole family. It occurs naturally in the feces of mammals and birds and is the primary contributor to fecal odor. In low concentrations, it has a flowery smell and is found in several flowers and essential oils, including those of orange blossoms, jasmine, and Ziziphus mauritiana . It has also been identified in certain cannabis varieties. [1]

Contents

It is used as a fragrance and fixative in many perfumes and as an aroma compound. Its name derives from the Greek root skato-, meaning feces. Skatole was discovered in 1877 by the German physician Ludwig Brieger (1849–1919). [2] [3] [4]

Original: "Ich habe mich zuerst mit der Untersuchung der flüchtigen Bestandtheile der Excremente aus sauerer Lösung beschäftigt. Es wurden dabei die flüchtigen Fettsäuren: Essigsäure, normale und Isobuttersäure, sowie die aromatischen Substanzen: Phenol, Indol und eine neue dem Indol verwandte Substanz, die ich Skatol nennen werde, erhalten."


Translation: "I was occupied initially with the investigation of the volatile components of excrement in acidic solution. One obtained thereby volatile fatty acids; acetic acid; normal and isobutyric acid; as well as the aromatic substances: phenol, indole and a new substance which is related to indole and which I will name 'skatole'." - Brieger (1878), page 130


Biosynthesis, chemical synthesis, and reactions

Skatole is derived from the amino acid tryptophan in the digestive tract of mammals. Tryptophan is converted to indoleacetic acid, which decarboxylates to give the methylindole. [5] [6]

Skatole can be synthesized via the Fischer indole synthesis. [7]

It gives a violet color upon treatment with potassium ferrocyanide.[ citation needed ]

Skatole, along with the fecal odorant indole, can be neutralized by combining it with other scents, by producing perfumes or air fresheners that lack skatole and indole. In a manner similar to noise-cancelling headphones, the scent produced by the resultant concentrations of skatole and indole relative to other substances in the freshener is thus "in-phase" and perceived as pleasant. [8]

Insect attractant

Skatole is one of many compounds that are attractive to males of various species of orchid bees, which apparently gather the chemical to synthesize pheromones; it is commonly used as bait for these bees for study. [9] It is also known for being an attractant for the Tasmanian grass grub beetle ( Aphodius tasmaniae ). [10]

Skatole has been shown to be an attractant to gravid mosquitoes in both field and laboratory conditions. Because this compound is present in feces, it is found in combined sewage overflows (CSO), as streams and lakes containing CSO water have untreated human and industrial waste. CSO sites are thus of particular interest when studying mosquito-borne diseases such as West Nile virus. [11]

Animal studies

Skatole occurs naturally in the feces of all species of mammals and birds, and in the bovine rumen. [12]

Skatole has been shown to cause pulmonary edema in goats, sheep, rats, and some strains of mice. It appears to selectively target club cells, which are the major site of cytochrome P450 enzymes in the lungs. These enzymes convert skatole to a reactive intermediate, 3-methyleneindolenine, which damages cells by forming protein adducts (see fog fever). [13]

With the testicular steroid androstenone, skatole is regarded as a principal determinant of boar taint. [14]

Skatole contributes to bad breath. [15]

Application

Skatole is the starting material in the synthesis of atiprosin.

See also

Related Research Articles

<span class="mw-page-title-main">Cadaverine</span> Foul-smelling diamine compound

Cadaverine is an organic compound with the formula (CH2)5(NH2)2. Classified as a diamine, it is a colorless liquid with an unpleasant odor. It is present in small quantities in living organisms but is often associated with the putrefaction of animal tissue.

<span class="mw-page-title-main">Tryptophan synthase</span>

Tryptophan synthase or tryptophan synthetase is an enzyme that catalyses the final two steps in the biosynthesis of tryptophan. It is commonly found in Eubacteria, Archaebacteria, Protista, Fungi, and Plantae. However, it is absent from Animalia. It is typically found as an α2β2 tetramer. The α subunits catalyze the reversible formation of indole and glyceraldehyde-3-phosphate (G3P) from indole-3-glycerol phosphate (IGP). The β subunits catalyze the irreversible condensation of indole and serine to form tryptophan in a pyridoxal phosphate (PLP) dependent reaction. Each α active site is connected to a β active site by a 25 angstrom long hydrophobic channel contained within the enzyme. This facilitates the diffusion of indole formed at α active sites directly to β active sites in a process known as substrate channeling. The active sites of tryptophan synthase are allosterically coupled.

<span class="mw-page-title-main">Tryptamine</span> Metabolite of the amino acid tryptophan

Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the first one being the heterocyclic nitrogen). The structure of tryptamine is a shared feature of certain aminergic neuromodulators including melatonin, serotonin, bufotenin and psychedelic derivatives such as dimethyltryptamine (DMT), psilocybin, psilocin and others. Tryptamine has been shown to activate trace amine-associated receptors expressed in the mammalian brain, and regulates the activity of dopaminergic, serotonergic and glutamatergic systems. In the human gut, symbiotic bacteria convert dietary tryptophan to tryptamine, which activates 5-HT4 receptors and regulates gastrointestinal motility. Multiple tryptamine-derived drugs have been developed to treat migraines, while trace amine-associated receptors are being explored as a potential treatment target for neuropsychiatric disorders.

<i>Cannabis sativa</i> Plant species

Cannabis sativa is an annual herbaceous flowering plant. The species was first classified by Carl Linnaeus in 1753. The specific epithet sativa means 'cultivated'. Indigenous to Eastern Asia, the plant is now of cosmopolitan distribution due to widespread cultivation. It has been cultivated throughout recorded history and used as a source of industrial fiber, seed oil, food, and medicine. It is also used as a recreation drug and for religious and spiritual purposes.

<span class="mw-page-title-main">Indole-3-acetic acid</span> Chemical compound

Indole-3-acetic acid is the most common naturally occurring plant hormone of the auxin class. It is the best known of the auxins, and has been the subject of extensive studies by plant physiologists. IAA is a derivative of indole, containing a carboxymethyl substituent. It is a colorless solid that is soluble in polar organic solvents.

The Japp–Klingemann reaction is a chemical reaction used to synthesize hydrazones from β-keto-acids and aryl diazonium salts. The reaction is named after the chemists Francis Robert Japp and Felix Klingemann.

Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi, from which it was first isolated in 1885 by Johan Fredrik Eykman. The elucidation of its structure was made nearly 50 years later.

The indole test is a biochemical test performed on bacterial species to determine the ability of the organism to convert tryptophan into indole. This division is performed by a chain of a number of different intracellular enzymes, a system generally referred to as "tryptophanase."

<span class="mw-page-title-main">Indole alkaloid</span> Class of alkaloids

Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known different compounds, it is one of the largest classes of alkaloids. Many of them possess significant physiological activity and some of them are used in medicine. The amino acid tryptophan is the biochemical precursor of indole alkaloids.

<span class="mw-page-title-main">Glucobrassicin</span> Chemical compound

Glucobrassicin is a type of glucosinolate that can be found in almost all cruciferous plants, such as cabbages, broccoli, mustards, and woad. As for other glucosinolates, degradation by the enzyme myrosinase is expected to produce an isothiocyanate, indol-3-ylmethylisothiocyanate. However, this specific isothiocyanate is expected to be highly unstable, and has indeed never been detected. The observed hydrolysis products when isolated glucobrassicin is degraded by myrosinase are indole-3-carbinol and thiocyanate ion, which are envisioned to result from a rapid reaction of the unstable isothiocyanate with water. However, a large number of other reaction products are known, and indole-3-carbinol is not the dominant degradation product when glucosinolate degradation takes place in crushed plant tissue or in intact plants.

Fog fever is a refeeding syndrome in cattle, clinically named acute bovine pulmonary emphysema and edema (ABPEE) and bovine atypical interstitial pneumonia. This veterinary disease in adult cattle follows an abrupt move from feedlot to 'foggage pasture'. Clinical signs begin within 1 to 14 days and death may follow within 2 to 4 days. The condition can affect up to 50% of the herd, and around 30% of affected cattle may die as a result. This metabolic nutritional-respiratory disturbance has also been reported in other ruminants and on a wide variety of grasses, alfalfa, rape, kale, and turnip tops.

<span class="mw-page-title-main">4-Chloroindole-3-acetic acid</span> Chemical compound

4-Chloroindole-3-acetic acid (4-Cl-IAA) is an organic compound that functions as a plant hormone.

In enzymology, an indole-3-acetaldehyde oxidase (EC 1.2.3.7) is an enzyme that catalyzes the chemical reaction

In enzymology, an indoleacetate—lysine synthetase (EC 6.3.2.20) is an enzyme that catalyzes the chemical reaction

In enzymology, an indoleacetylglucose-inositol O-acyltransferase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Yuehchukene</span> Chemical compound

Yuehchukene is a dimeric indole alkaloid natural product that possesses anti-fertility and estrogenic activities. Yuehchukene is isolated from the roots of Murraya paniculata and other species of the plant genus Murraya. Its natural abundance is in the range of 10-52 ppm.

<span class="mw-page-title-main">Indole</span> Chemical compound

Indole is an aromatic, heterocyclic, organic compound with the formula C8H7N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environment and can be produced by a variety of bacteria. As an intercellular signal molecule, indole regulates various aspects of bacterial physiology, including spore formation, plasmid stability, resistance to drugs, biofilm formation, and virulence. The amino acid tryptophan is an indole derivative and the precursor of the neurotransmitter serotonin.

<span class="mw-page-title-main">Tryptophol</span> Chemical compound

Tryptophol is an aromatic alcohol that induces sleep in humans. It is found in wine as a secondary product of ethanol fermentation. It was first described by Felix Ehrlich in 1912. It is also produced by the trypanosomal parasite in sleeping sickness.

<span class="mw-page-title-main">3-Indolepropionic acid</span> Chemical compound

3-Indolepropionic acid (IPA), or indole-3-propionic acid, has been studied for its therapeutic therapeutic value in the treatment of Alzheimer's disease. As of 2022 IPA shows potential in the treatment of this disease, though the therapeutic effect of IPA depends on dose and time of therapy initiation.

Indoleacetate decarboxylase (IAD) is a glycyl radical enzyme that catalyses the decarboxylation of indoleacetate to form skatole, which is a malodorous organic compound that gives animal faeces their characteristic smell. This decarboxylation is the last step of the tryptophan fermentation in some types of anaerobic bacteria.

References

  1. Oswald, Iain W. H.; Paryani, Twinkle R.; Sosa, Manuel E.; Ojeda, Marcos A.; Altenbernd, Mark R.; Grandy, Jonathan J.; Shafer, Nathan S.; Ngo, Kim; Peat, Jack R.; Melshenker, Bradley G.; Skelly, Ian; Koby, Kevin A.; Page, Michael F. Z.; Martin, Thomas J. (2023-10-12). "Minor, Nonterpenoid Volatile Compounds Drive the Aroma Differences of Exotic Cannabis". ACS Omega. 8 (42): 39203–39216. doi: 10.1021/acsomega.3c04496 . ISSN   2470-1343. PMC   10601067 . PMID   37901519.
  2. Brieger, Ludwig (1877). "Über die flüchtigen Bestandtheile der menschlichen Excremente" [On the volatile components of human excrement]. Berichte der Deutschen Chemischen Gesellschaft. 10: 1027–1032. doi:10.1002/cber.187701001288 . Retrieved 3 November 2020.
  3. Brieger, Ludwig (1878). "Über die flüchtigen Bestandtheile der menschlichen Excremente". Journal für Praktische Chemie. 17: 124–138. doi:10.1002/prac.18780170111 . Retrieved 3 November 2020. Das Skatol ... (von το σχατος = faeces) ... (Skatole ... (from το σχατος = feces....)
  4. Brieger, Ludwig (1879). "Über Skatol" [On skatole]. Berichte der Deutschen Chemischen Gesellschaft. 12 (2): 1985–1988. doi:10.1002/cber.187901202206 . Retrieved 3 November 2020.
  5. Whitehead, T. R.; Price, N. P.; Drake, H. L.; Cotta, M. A. (25 January 2008). "Catabolic pathway for the production of skatole and indoleacetic acid by the acetogen Clostridium drakei, Clostridium scatologenes, and swine manure". Applied and Environmental Microbiology. 74 (6): 1950–3. Bibcode:2008ApEnM..74.1950W. doi:10.1128/AEM.02458-07. PMC   2268313 . PMID   18223109.
  6. Yokoyama, M. T.; Carlson, J. R. (1979). "Microbial metabolites of tryptophan in the intestinal tract with special reference to skatole". The American Journal of Clinical Nutrition. 32 (1): 173–178. doi: 10.1093/ajcn/32.1.173 . PMID   367144.
  7. Emil Fischer (1886) "Indole aus Phenylhydrazin" (Indole from phenylhydrazine), Annalen der Chemie, vol. 236, pages 126-151; for Fischer's synthesis of skatole, see page 137. (Fischer was not the first to prepare skatole. It was prepared, via other methods, in 1880 by von Baeyer, and in 1883 by Otto Fischer and German and by Fileti.)
  8. Holusha, John (15 July 1990). "Technology; Making Bad Smell Good by Tricking the Nose". The New York Times.
  9. Schiestl, F.P. & Roubik, D.W. (2004). "Odor Compound Detection in Male Euglossine Bees". Journal of Chemical Ecology. 29 (1): 253–257. doi:10.1023/A:1021932131526. hdl: 20.500.11850/57276 . PMID   12647866. S2CID   2845587.
  10. Osborne, G. O.; Penman, D. R.; Chapman, R. B. (1975). "Attraction of Aphodius tasmaniae Hope to skatole". Australian Journal of Agricultural Research . 26 (5): 839–841. doi:10.1071/AR9750839.
  11. Beechler, J W., J G Miller, and M S Mulla (1994). "Field evaluation of synthetic compounds mediating oviposition in Culex mosquitoes (Diptera: Culicidae)". J Chem Ecol. 20 (2): 281–291. doi:10.1007/BF02064436. PMID   24242053. S2CID   23784247.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. Yokoyama, M. T.; Carlson, J. R.; Holdeman, L. V. (1977). "Isolation and characteristics of a skatole-producing Lactobacillus sp. from the bovine rumen". Applied and Environmental Microbiology. 34 (6): 837–842. Bibcode:1977ApEnM..34..837Y. doi:10.1128/AEM.34.6.837-842.1977. PMC   242757 . PMID   563703.
  13. Miller, M; Kottler, S; Ramos-Vara, J; Johnson, P; Ganjam, V; Evans, T (2003). "3-Methylindole Induces Transient Olfactory Mucosal Injury in Ponies". Veterinary Pathology . 40 (4): 363–70. doi: 10.1354/vp.40-4-363 . PMID   12824507.
  14. Wesoly, R.; Weiler, U. (2012). "Nutritional Influences on Skatole Formation and Skatole Metabolism in the Pig". Animals. 2 (2): 221–242. doi: 10.3390/ani2020221 . PMC   4494329 . PMID   26486918.
  15. Franklin, Deborah (1 May 2013). "To Beat Bad Breath, Keep the Bacteria in Your Mouth Happy". Scientific American. 308 (5): 30, 32. doi:10.1038/scientificamerican0513-30. PMID   23627212 . Retrieved 3 November 2020.