Menthofuran is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

found in a variety of

essential oil An essential oil is a concentrated hydrophobic liquid containing volatile (easily evaporated at normal temperatures) chemical compounds from plants. Essential oils are also known as volatile oils, ethereal oils, aetheroleum, or simply as the o ...

s including that of pennyroyal (''Mentha pulegium''). It is highly toxic and believed to be the primary toxin in pennyroyal responsible for its potentially fatal effects. After ingestion of menthofuran, it is metabolically activated to chemically reactive intermediates that are

hepatotoxic Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fro ...

Biosynthesis

Menthofuran is produced biosynthetically from

pulegone Pulegone is a naturally occurring organic compound obtained from the essential oils of a variety of plants such as ''Nepeta cataria'' (catnip), ''Mentha piperita'', and pennyroyal. It is classified as a monoterpene. Pulegone is a clear colorles ...

by the enzyme

menthofuran synthase (+)-Menthofuran synthase (, ''menthofuran synthase'', ''(+)-pulegone 9-hydroxylase'', ''(+)-MFS'', ''cytochrome P450 menthofuran synthase'') is an enzyme with systematic name ''(+)-pulegone,NADPH:oxygen oxidoreductase (9-hydroxylating)''. This enz ...

. :

Chemistry

Synthesis

Menthofuran can be synthesized from 5-methylcyclohexane-1,3-dione and allenyldimethylsulfonium bromide in two steps via a furannulation strategy consisting of enolate addition and rearrangement.

Pharmacology

Menthofuran is a metabolite of pulegone. Both ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

'' and ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'' studies have found the pulegone metabolite menthofuran to be an inhibitor of

CYP2A6 Cytochrome P450 2A6 (abbreviated CYP2A6) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. CYP2A6 is the primary enzyme responsible for the oxidation of nicotine and ...

. Menthofuran may deplete glutathione levels, leaving hepatocytes vulnerable to free radical damage.

References

{{reflist Monoterpenes Furans Toxins Plant toxins