Tremetone is a constituent of the

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

compound tremetol, found in snakeroot (''

Ageratina altissima ''Ageratina altissima'', also known as white snakeroot, richweed, or white sanicle, is a poisonous perennial herb in the family Asteraceae, native to eastern and central North America. An older binomial name for this species is ''Eupatorium rugo ...

''), that contributes to cause

milk sickness Milk sickness, also known as tremetol vomiting, is a kind of poisoning characterized by trembling, vomiting, and severe intestinal pain that affects individuals who ingest milk, other dairy products, or meat from a cow that has fed on white sna ...

in humans and trembles in livestock. Tremetone is the main constituent of at least 11 chemically related substances in tremetol. Tremetone is toxic to fish, but not to chicken, and is therefore not the major toxic compound in tremetol. Tremetol can be found in a

number A number is a mathematical object used to count, measure, and label. The most basic examples are the natural numbers 1, 2, 3, 4, and so forth. Numbers can be represented in language with number words. More universally, individual numbers can ...

of different species of the family

Asteraceae Asteraceae () is a large family (biology), family of flowering plants that consists of over 32,000 known species in over 1,900 genera within the Order (biology), order Asterales. The number of species in Asteraceae is rivaled only by the Orchi ...

, including snakeroot and rayless goldenrod ('' Isocoma pluriflora'').

Synthesis

Tremetol, an oil with a straw-colored tinge, was first isolated from white snakeroot by J.F. Couch in 1929.

Column chromatography Column chromatography in chemistry is a chromatography method used to isolate a single chemical compounds, chemical compound from a mixture. Chromatography is able to separate substances based on differential absorption of compounds to the adsorbe ...

of tremetol yielded a hydrocarbon, two steroids, and three ketones. Further isolation experiments revealed that tremetone is the major ketone constituent of the compound tremetol. Hence, tremetone was hypothesized to be responsible for the “trembles” that characterize the milk sickness disease. Tremetone was first synthesized in July 1963 by DeGraw, Bowen, and Bonner.{{cite journal , doi=10.1016/0040-4020(63)80002-2 , title=The synthesis of racemic tremetone , journal=Tetrahedron , volume=19 , issue=1 , pages=19–24 , year=1963 , last1=Degraw , first1=J.I. , last2=Bowen , first2=D.M. , last3=Bonner , first3=W.A. This synthesis is illustrated below. The final dehydration step was accomplished by treatment with phosphoryl chloride/pyridine at 75 °C. This synthesis had a 75% yield, but the final product was a

racemate In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...

that would not suitably undergo chiral resolution. This prevented isolation of the natural levorotary enantiomer of tremetone; thus limiting the ability to further analyze its biological mechanisms. However, in November 1963, the enantiomers of tremetone were isolated by Bowen, et al. via the synthesis illustrated below. Resolution of enantiomers occurred by co-crystallization of the acid following Na/Hg reduction.

References

Piceol ethers Plant toxins Benzofurans Alkene derivatives Aromatic ketones

Synthesis

See also

References