Brucine

Brucine is an alkaloid closely related to strychnine, most commonly found in the Strychnos nux-vomica tree. Brucine poisoning is rare, since it is usually ingested with strychnine, and strychnine is more toxic than brucine. In chemical synthesis, it can be used as a tool for stereospecific chemical syntheses.
Brucine's name derives from this of the genus Brucea, named after James Bruce who brought back Brucea antidysenterica from Ethiopia.

History

Brucine was discovered in 1819 by the French chemist Pelletier and the French pharmacist Caventou in the bark of the Strychnos nux-vomica tree. While its chemical structure was not deduced until much later, it was determined that it was closely related to strychnine in 1884 when the chemist Hanssen converted both strychnine and brucine into the same molecule.

Identification

Brucine can be detected and quantified using liquid chromatography-mass spectrometry. Historically, brucine was distinguished from strychnine by its reactivity toward chromic acid.

Applications

Chemical applications

Since brucine is a large chiral molecule, it has been used in chiral resolution. Fisher first reported its use as a resolving agent in 1899, and it was the first natural product used as an organocatalyst in a reaction resulting in an enantiomeric enrichment by Marckwald, in 1904. Its bromide salt has been used as the stationary phase in HPLC to selectively bind one of two an ionic enantiomers. Brucine has also been used for fractional crystallization in acetone to resolve dihydroxy fatty acids, as well as diarylcarbinols. If formic acid is added to a mixture of brucine and potassium nitrate, its color instantly turns red. This reaction has been used for the direct colorimetric detection of nitrates.

Medical applications

While brucine has been shown to have good anti-tumor effects, on both hepatocellular carcinoma and breast cancer, its narrow therapeutic window has limited its use as a treatment for cancer.
Brucine is also used in traditional Chinese medicine as an anti-inflammatory and analgesic agent, as well as in some Ayurveda and homeopathy drugs.

Alcohol denaturant

Brucine is one of the many chemicals used as a denaturant to make alcohol unfit for human consumption.

Cultural references

One of the most famous cultural references to brucine occurs in The Count of Monte Cristo, the novel by French author Alexandre Dumas. In a discussion of mithridatism, Monte Cristo states:
Brucine is also mentioned in the 1972 version of The Mechanic, in which the hitman Steve McKenna betrays his mentor, ageing hitman Arthur Bishop, using a celebratory glass of wine spiked with brucine, leaving Bishop to die of an apparent heart attack.
Such fictions run contrary to reality in the very properties which make brucine useful as a denaturant, and useless as a covert poison. While being only about one-eighth as toxic as strychnine, its threshold of bitterness occurs at 69 % greater dilution. A drink laden with brucine, overwhelmingly bitter at far below lethal concentration, would cause an intended victim to gag on the first sip.

Safety

Brucine intoxication occurs very rarely, since it is usually ingested with strychnine. Symptoms of brucine intoxication include muscle spasms, convulsions, rhabdomyolysis, and acute kidney injury. Brucine’s mechanism of action closely resembles that of strychnine. It acts as an antagonist at glycine receptors and paralyzes inhibitory neurons.
The probable lethal dose of brucine in adults is 1 g. In other animals, the LD₅₀ varies considerably.

Animal	Route of entry	LD₅₀
Mouse	Subcutaneous	60 mg/kg
Rat	Intraperitoneal	91 mg/kg
Rabbit	Oral	4 mg/kg