Tremetone is a chemical compound found in tremetol, a

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...

mixture from 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 causes

milk sickness Milk sickness, also known as tremetol vomiting or, in animals, as trembles, 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 ...

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 original 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 c ...

of different species of the family

Asteraceae The family Asteraceae, alternatively Compositae, consists of over 32,000 known species of flowering plants in over 1,900 genera within the order Asterales. Commonly referred to as the aster, daisy, composite, or sunflower family, Compositae w ...

, including snakeroot and rayless goldenrod (''

Isocoma pluriflora ''Isocoma pluriflora'', commonly called southern jimmyweed or southern goldenbush, is a North American species of flowering perennial herbs in the family Asteraceae. It grows in northern Mexico (Baja California Sur, Sonora, Chihuahua, Coahuila, ...

'').

Synthesis

Tremetol, an oil with a straw-colored tinge, was first isolated from white snakeroot by J.F. Couch in 1929. Column chromatography 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 one that has equal amounts 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 racemates. ...

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

Synthesis

See also

References