Ascaridole
Encyclopedia
Ascaridole is a natural organic compound
classified as a bicyclic monoterpene
that has an unusual bridging peroxide
functional group. It is a colorless liquid with a pungent smell and taste that is soluble in most organic solvents. Like other low molecular weight organic peroxide
s, it is unstable and prone to explosion when heated or treated with organic acids. Ascaridole determines the specific flavor of the Chilean tree boldo
and is a major constituent of the oil of Mexican Tea
(wormseed). It is a component of natural medicine, tonic drinks and food flavoring in Latin American cuisine. As part of the oil, ascaridole is used as an anthelmintic
drug that expels parasitic worm
s from plants, domestic animals and the human body.
. It was isolated from chenopodium
oil and named by Hüthig in 1908 who described its explosive character and determined its chemical formula as C10H16O2. Hüthig also noted the indifference of ascaridole to aldehydes, ketones or phenols that characterized it as non-alcohol. When reacted with sulfuric acid, or reduced
with zinc powder and acetic acid
, ascaridole formed cymene
. These results were confirmed in a detailed study by E. K. Nelson in 1911, in particular that ascaridole explodes upon heating, reacting with sulfuric, hydrochloric, nitric or phosphoric acid
s. Nelson showed that the new substance contained neither hydroxyl nor carbonyl group and that upon oxidation with iron sulfate
it forms a glycol, now known as ascaridole glycol C10H18O3. The glycol is more stable than ascaridole and has a higher melting point of about 64 °C, boiling point of 272 °C, and density of 1.098 g/cm3. Nelson also predicted the chemical structure of ascaridole which was almost correct, but had the peroxide bridge not along the molecular axis, but between the other, off-axis carbon atoms. This structure was corrected by Otto Wallach
in 1912.
The first laboratory synthesis was demonstrated in 1944 by Günter Schenck and Karl Ziegler
and might be regarded as mimicking the natural production of ascaridole. The process starts from α-terpinene
which reacts with oxygen under the influence of chlorophyll
and light. Under these conditions singlet oxygen
is generated which reacts in a Diels-Alder reaction
with the diene system in the terpinene. Since 1945, this reaction has been adopted into the industry for large-scale production of ascaridole in Germany. It was then used as an inexpensive drug against intestinal worms.
s, it is unstable and prone to explosion when heated to a temperature above 130 °C or treated with organic acids. When heated, it emits fumes which are poisonous and possibly carcinogenic.
The specific flavor of the Chilean tree boldo
(Peumus boldus) primarily originates from ascaridole. Ascaridole is also a major component of epazote
(or Mexican Tea, Dysphania ambrosioides formerly Chenopodium ambrosioides) where it typically constitutes between 16 and 70% of the plant's essential oil
. The content of ascaridole in the plant depends on cultivation and is maximal when the nitrogen to phosphorus ratio in the soil is about 1:4. It also changes though the year peaking around the time when the plant seeds become mature.
drug that expels parasitic worm
s (helminths) from body and plants. This property gave the name to this chemical, after Ascaris
– a genus of the large intestinal roundworms. In the early 1900s, it was a major remedy against intestinal parasites in humans, cats, dogs, goats, sheep, chickens, horses and pigs, and it is still used in livestock, particularly in the Central American countries. The dosage was specified by the ascaridole content in the oil, which was traditionally determined with an assay
developed by Nelson in 1920. It was later substituted with modern gas chromatography and mass spectrometry
methods. The worms and their larvae were killed by immersion in a solution of ascaridole in water (about 0.015 vol%) for 18 hours at 50 °F (10 °C) or 12 hours at 60 °F (15.6 °C) or 6 hours at 65 to 70 °F (18.3 to 21.1 C). Meanwhile, such immersion did not damage the roots and stems of plants such as Iris
, Phlox
, Sedum
and others at 70 °F (21.1 °C) for 15 hours or longer.
The wormseed oil itself (Mexican Tea) is traditionally used in Mexican cuisine for flavoring dishes and preventing flatulence
from bean-containing food. It is also part of tonic drinks and infusions to expel intestinal parasite
s and treat asthma, arthritis, dysentery, stomach ache, malaria and nervous diseases in folk medicine practiced in North and South Americas, China and Turkey.
, tinnitus
, temporal deafness and blindness. Prolonged action induces depression of the central nervous system
and delirium which transits into convulsions and coma. Long-term effects include pulmonary edema
(fluid accumulation
in the lung
s), hematuria
and albuminuria
(presence of red blood cells and proteins in the urine
, respectively) and jaundice
(yellowish pigmentation of the skin). Fatal doses of wormseed oil were reported as one teaspoon for a 14 month old baby (at once) and daily administration of 1 mL over three weeks to a 2 year-old child. Ascaridole is also carcinogenic in rats.
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
classified as a bicyclic monoterpene
Monoterpene
Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16. Monoterpenes may be linear or contain rings...
that has an unusual bridging peroxide
Organic peroxide
Organic peroxides are organic compounds containing the peroxide functional group . If the R' is hydrogen, the compound is called an organic hydroperoxide. Peresters have general structure RCOOR. The O-O bond easily breaks and forms free radicals of the form RO·...
functional group. It is a colorless liquid with a pungent smell and taste that is soluble in most organic solvents. Like other low molecular weight organic peroxide
Organic peroxide
Organic peroxides are organic compounds containing the peroxide functional group . If the R' is hydrogen, the compound is called an organic hydroperoxide. Peresters have general structure RCOOR. The O-O bond easily breaks and forms free radicals of the form RO·...
s, it is unstable and prone to explosion when heated or treated with organic acids. Ascaridole determines the specific flavor of the Chilean tree boldo
Boldo
Peumus boldus, the only species in the genus Peumus, is commonly known as Boldo . This tree of the family Monimiaceae is natively endemic to the central region of Chile, occurring from 33° to 40° southern latitude...
and is a major constituent of the oil of Mexican Tea
Epazote
Epazote, wormseed, Jesuit's tea, Mexican tea, Paico or Herba Sancti Mariæ is an herb native to Central America, South America, and southern Mexico....
(wormseed). It is a component of natural medicine, tonic drinks and food flavoring in Latin American cuisine. As part of the oil, ascaridole is used as an anthelmintic
Anthelmintic
Anthelmintics or antihelminthics are drugs that expel parasitic worms from the body, by either stunning or killing them. They may also be called vermifuges or vermicides .-Pharmaceutical classes:...
drug that expels parasitic worm
Parasitic worm
Parasitic worms or helminths are a division of eukaryoticparasites that, unlike external parasites such as lice and fleas, live inside their host. They are worm-like organisms that live and feed off living hosts, receiving nourishment and protection while disrupting their hosts' nutrient...
s from plants, domestic animals and the human body.
History
Ascaridole was the first, and for a long time only, discovered naturally occurring organic peroxideOrganic peroxide
Organic peroxides are organic compounds containing the peroxide functional group . If the R' is hydrogen, the compound is called an organic hydroperoxide. Peresters have general structure RCOOR. The O-O bond easily breaks and forms free radicals of the form RO·...
. It was isolated from chenopodium
Chenopodium
Chenopodium is a genus of about 150 species of perennial or annual herbaceous flowering plants known as the goosefoots, which occur almost anywhere in the world. It is placed in the family Amaranthaceae in the APG II system; older classifications separate it and its relatives as Chenopodiaceae, but...
oil and named by Hüthig in 1908 who described its explosive character and determined its chemical formula as C10H16O2. Hüthig also noted the indifference of ascaridole to aldehydes, ketones or phenols that characterized it as non-alcohol. When reacted with sulfuric acid, or reduced
with zinc powder and acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
, ascaridole formed cymene
Cymene
Cymene, or p-cymene, is a naturally occurring aromatic organic compound. It is classified as a hydrocarbon related to a monoterpene. Its structure consists of a benzene ring para-substituted with a methyl group and an isopropyl group...
. These results were confirmed in a detailed study by E. K. Nelson in 1911, in particular that ascaridole explodes upon heating, reacting with sulfuric, hydrochloric, nitric or phosphoric acid
Phosphoric acid
Phosphoric acid, also known as orthophosphoric acid or phosphoric acid, is a mineral acid having the chemical formula H3PO4. Orthophosphoric acid molecules can combine with themselves to form a variety of compounds which are also referred to as phosphoric acids, but in a more general way...
s. Nelson showed that the new substance contained neither hydroxyl nor carbonyl group and that upon oxidation with iron sulfate
Iron sulfate
Iron sulfate may refer to:*Ferrous sulphate, Iron sulfate, FeSO4*Ferric sulphate, Iron sulfate, Fe23...
it forms a glycol, now known as ascaridole glycol C10H18O3. The glycol is more stable than ascaridole and has a higher melting point of about 64 °C, boiling point of 272 °C, and density of 1.098 g/cm3. Nelson also predicted the chemical structure of ascaridole which was almost correct, but had the peroxide bridge not along the molecular axis, but between the other, off-axis carbon atoms. This structure was corrected by Otto Wallach
Otto Wallach
Otto Wallach was a German chemist and recipient of the 1910 Nobel prize in Chemistry for his work on alicyclic compounds.-Biography:...
in 1912.
The first laboratory synthesis was demonstrated in 1944 by Günter Schenck and Karl Ziegler
Karl Ziegler
Karl Waldemar Ziegler was a German chemist who won the Nobel Prize in Chemistry in 1963, with Giulio Natta, for work on polymers. The Nobel Committee recognized his "excellent work on organometallic compounds [which]...led to new polymerization reactions and ... paved the way for new and highly...
and might be regarded as mimicking the natural production of ascaridole. The process starts from α-terpinene
Terpinene
The terpinenes are three isomeric hydrocarbons that are classified as terpenes. They each have the same molecular formula and carbon framework, but they differ in the position of carbon-carbon double bonds. α-Terpinene has been isolated from cardamom and marjoram oils, and from other natural...
which reacts with oxygen under the influence of chlorophyll
Chlorophyll
Chlorophyll is a green pigment found in almost all plants, algae, and cyanobacteria. Its name is derived from the Greek words χλωρος, chloros and φύλλον, phyllon . Chlorophyll is an extremely important biomolecule, critical in photosynthesis, which allows plants to obtain energy from light...
and light. Under these conditions singlet oxygen
Singlet oxygen
Singlet oxygen is the common name used for the diamagnetic form of molecular oxygen , which is less stable than the normal triplet oxygen. Because of its unusual properties, singlet oxygen can persist for over an hour at room temperature, depending on the environment...
is generated which reacts in a Diels-Alder reaction
Diels-Alder reaction
The Diels–Alder reaction is an organic chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene system. The reaction can proceed even if some of the atoms in the newly formed ring are not carbon...
with the diene system in the terpinene. Since 1945, this reaction has been adopted into the industry for large-scale production of ascaridole in Germany. It was then used as an inexpensive drug against intestinal worms.
Properties
Ascaridole is a colorless liquid that is soluble in most organic solvents. It is toxic and has a pungent, unpleasant smell and taste. Like other pure, low molecular weight organic peroxideOrganic peroxide
Organic peroxides are organic compounds containing the peroxide functional group . If the R' is hydrogen, the compound is called an organic hydroperoxide. Peresters have general structure RCOOR. The O-O bond easily breaks and forms free radicals of the form RO·...
s, it is unstable and prone to explosion when heated to a temperature above 130 °C or treated with organic acids. When heated, it emits fumes which are poisonous and possibly carcinogenic.
Occurrence
Boldo
Peumus boldus, the only species in the genus Peumus, is commonly known as Boldo . This tree of the family Monimiaceae is natively endemic to the central region of Chile, occurring from 33° to 40° southern latitude...
(Peumus boldus) primarily originates from ascaridole. Ascaridole is also a major component of epazote
Epazote
Epazote, wormseed, Jesuit's tea, Mexican tea, Paico or Herba Sancti Mariæ is an herb native to Central America, South America, and southern Mexico....
(or Mexican Tea, Dysphania ambrosioides formerly Chenopodium ambrosioides) where it typically constitutes between 16 and 70% of the plant's essential oil
Essential oil
An essential oil is a concentrated hydrophobic liquid containing volatile aroma compounds from plants. Essential oils are also known as volatile oils, ethereal oils or aetherolea, or simply as the "oil of" the plant from which they were extracted, such as oil of clove...
. The content of ascaridole in the plant depends on cultivation and is maximal when the nitrogen to phosphorus ratio in the soil is about 1:4. It also changes though the year peaking around the time when the plant seeds become mature.
Applications
Ascaridole is mainly used as an anthelminticAnthelmintic
Anthelmintics or antihelminthics are drugs that expel parasitic worms from the body, by either stunning or killing them. They may also be called vermifuges or vermicides .-Pharmaceutical classes:...
drug that expels parasitic worm
Parasitic worm
Parasitic worms or helminths are a division of eukaryoticparasites that, unlike external parasites such as lice and fleas, live inside their host. They are worm-like organisms that live and feed off living hosts, receiving nourishment and protection while disrupting their hosts' nutrient...
s (helminths) from body and plants. This property gave the name to this chemical, after Ascaris
Ascaris
Ascaris is a genus of parasitic nematode worms known as the "giant intestinal roundworms". One species, A. suum, typically infects pigs, while another, A. lumbricoides, affects human populations, typically in sub-tropical and tropical areas with poor sanitation. A...
– a genus of the large intestinal roundworms. In the early 1900s, it was a major remedy against intestinal parasites in humans, cats, dogs, goats, sheep, chickens, horses and pigs, and it is still used in livestock, particularly in the Central American countries. The dosage was specified by the ascaridole content in the oil, which was traditionally determined with an assay
Assay
An assay is a procedure in molecular biology for testing or measuring the activity of a drug or biochemical in an organism or organic sample. A quantitative assay may also measure the amount of a substance in a sample. Bioassays and immunoassays are among the many varieties of specialized...
developed by Nelson in 1920. It was later substituted with modern gas chromatography and mass spectrometry
Mass spectrometry
Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...
methods. The worms and their larvae were killed by immersion in a solution of ascaridole in water (about 0.015 vol%) for 18 hours at 50 °F (10 °C) or 12 hours at 60 °F (15.6 °C) or 6 hours at 65 to 70 °F (18.3 to 21.1 C). Meanwhile, such immersion did not damage the roots and stems of plants such as Iris
Iris (plant)
Iris is a genus of 260-300species of flowering plants with showy flowers. It takes its name from the Greek word for a rainbow, referring to the wide variety of flower colors found among the many species...
, Phlox
Phlox
Phlox is a genus of 67 species of perennial and annual plants found mostly in North America in diverse habitats from alpine tundra to open woodland and prairie. Some flower in spring, others in summer and autumn....
, Sedum
Sedum
Sedum is a large genus of flowering plants in the family Crassulaceae, members of which are commonly known as stonecrops. It contains around 400 species of leaf succulents that are found throughout the Northern Hemisphere, varying from annual and creeping herbs to shrubs. The plants have...
and others at 70 °F (21.1 °C) for 15 hours or longer.
The wormseed oil itself (Mexican Tea) is traditionally used in Mexican cuisine for flavoring dishes and preventing flatulence
Flatulence
Flatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
from bean-containing food. It is also part of tonic drinks and infusions to expel intestinal parasite
Intestinal parasite
Intestinal parasites are parasites that populate the gastro-intestinal tract in humans and other animals. They can live throughout the body, but most prefer the intestinal wall. Means of exposure include: ingestion of undercooked meat, drinking infected water, and skin absorption...
s and treat asthma, arthritis, dysentery, stomach ache, malaria and nervous diseases in folk medicine practiced in North and South Americas, China and Turkey.
Health issues
The usage of wormseed oil on humans is limited by the toxicity of ascaridole and has therefore been discouraged. In high doses, wormseed oil causes irritation of skin and mucous membrane, nausea, vomiting, constipation, headache, vertigoVertigo
Vertigo is a form of dizziness.Vertigo may also refer to:* Vertigo , a 1958 film by Alfred Hitchcock**Vertigo , its soundtrack** Vertigo effect, or Dolly zoom, a special effect in film, named after the movie...
, tinnitus
Tinnitus
Tinnitus |ringing]]") is the perception of sound within the human ear in the absence of corresponding external sound.Tinnitus is not a disease, but a symptom that can result from a wide range of underlying causes: abnormally loud sounds in the ear canal for even the briefest period , ear...
, temporal deafness and blindness. Prolonged action induces depression of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
and delirium which transits into convulsions and coma. Long-term effects include pulmonary edema
Pulmonary edema
Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
(fluid accumulation
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
in the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s), hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
and albuminuria
Albuminuria
Albuminuria is a pathological condition wherein albumin is present in the urine. It is a type of proteinuria.Measurement=The amount of protein being lost in the urine can be quantified by collecting the urine for 24 hours, measuring a sample of the pooled urine, and extrapolating to the volume...
(presence of red blood cells and proteins in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, respectively) and jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
(yellowish pigmentation of the skin). Fatal doses of wormseed oil were reported as one teaspoon for a 14 month old baby (at once) and daily administration of 1 mL over three weeks to a 2 year-old child. Ascaridole is also carcinogenic in rats.