Brucine

Brucine
Names
IUPAC name
2,​3-​dimethoxystrychnidin-​10-​one
Other names
2,3-Dimethoxystrychnine
10,11-Dimethoxystrychnine
Identifiers
357-57-3 YesY
3D model (Jmol) Interactive image
ChEMBL ChEMBL501756 YesY
ChemSpider 390579 YesY
ECHA InfoCard 100.006.014
342
KEGG C09084 YesY
PubChem 442021
UNII 6NG17YCK6H YesY
Properties
C23H26N2O4
Molar mass 394.47 g·mol−1
Melting point 178 °C (352 °F; 451 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Brucine, an alkaloid closely related to strychnine, is 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 synthetic chemistry, it can be used as a tool for stereospecific chemical syntheses.

History

Brucine was first discovered in 1819 by Pelletier and Caventou in the bark of the Strychnos nux vomica tree.[1] While its 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.[2]

Toxicity

The probable fatal dose of brucine in adults is 1 g.[3] In other animals, the LD50 varies considerably.[4]

Animal Route of Entry LD50
Rat Oral 1 mg/kg
Rat Ipr 91 mg/kg
Rabbit Oral 4 mg/kg

Mechanism of action

Brucine’s mechanism of action closely resembles that of strychnine. It acts as an antagonist at glycine receptors and paralyzes inhibitory neurons.

Glycine binds to receptors on inhibitory neurons to terminate action potentials. Its binding terminates an action potential by causing an influx of chloride ions into the neuron, repolarizing the neuron to its resting potential. Brucine also binds to these receptors, but its binding does not trigger an influx of chloride ions. Brucine's toxicity arises because glycine is blocked from binding to its receptors, making inhibition of an action potential more difficult.

Identification and treatment

Historically, brucine was distinguished from strychnine by the addition of chromic acid in H2SO4, since it does not give off the series of colors that is characteristic of strychnine.[5]

Today, pure brucine intoxication occurs very rarely, since it is usually ingested with strychnine. Symptoms of brucine intoxication include muscle spasms, convulsions, rhabdomyolysis, and acute renal failure. Brucine can be detected and quantified using liquid chromatography-mass spectrometry.[6]

Applications

Chemical applications

Since brucine is a large chiral molecule, it has been used as an enantioselective recognition agent using 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 a successful enantiomeric enrichment by Marckwald, in 1904.[7] Its bromide salt has been used as the stationary phase in HPLC in order to selectively bind one of two anionic enantiomers.[8] Brucine has also been used in fractional distillation in acetone in order to resolve dihydroxy fatty acids,[9] as well as diarylcarbinols.[10]

Medical applications

While brucine has been shown to have good anti-tumor effects, on both hepatocellular carcinoma[11] and breast cancer,[12] 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,[13] as well as in some Ayurveda and homeopathy drugs.[14]


Alcohol Denaturant

Brucine is one of the many chemicals used as a denaturant to make alcohol unfit for human consumption.[15]

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:

“Well, suppose, then, that this poison was brucine, and you were to take a milligramme the first day, two milligrams the second day, and so on…at the end of a month, when drinking water from the same carafe, you would kill the person who drank with you, without your perceiving…that there was any poisonous substance mingled with this water.”[16]

Brucine in also mentioned in the 1972 version of The Mechanic, in which the hitman Steve McKenna betrays his mentor, aging hitman Arthur Bishop, using a celebratory glass of wine spiked with brucine, leaving Bishop to die of an apparent heart attack.[17]

References

  1. ↑ Wormley, T (1869). Micro-chemistry of poisons including their physiological, pathological, and legal relations : Adapted to the use of the medical jurist, physician, and general chemist. New York: W. Wood.
  2. ↑ Buckingham, J (2007). Bitter Nemesis: The Intimate History of Strychnine. CRC Press. p. 225.
  3. ↑ Gosselin, R. E.; Smith, R. P.; Hodge, H. C. (1984). Clinical Toxicology of Commercial Products (5 ed.). Baltimore/London: Williams & Wilkins.
  4. ↑ Goodman, L. (2006). Goodman & Gilman's the pharmacological basis of therapeutics (11 ed.). New York: McGraw-Hill.
  5. ↑ Glasby, J. (1975). Encyclopedia of the alkaloids. New York: Plenum Press. p. 214.
  6. ↑ Teske, J; Weller, J; Albrecht, U; Fieguth, A (2011). "Fatal Intoxication Due to Brucine". Journal of Analytical Toxicology. 35: 248–253. doi:10.1093/anatox/35.4.248.
  7. ↑ Koskinen, A (1993). Asymmetric synthesis of natural products. Chichester: J. Wiley. pp. 17, 28–29.
  8. ↑ Zarbua, K; Kral, V. "Quaternized brucine as a novel chiral selector". Tetrahedron: Asymmetry. 13: 2567–2570. doi:10.1016/s0957-4166(02)00715-2.
  9. ↑ Malkar, N; Kumar, V (1998). "Optical resolution of (±)-Threo-9,10,16-trihydroxy hexadecanoic acid using (−)brucine". Journal of the American Oil Chemists' Society. 75 (10): 1461–1463. doi:10.1007/s11746-998-0202-9.
  10. ↑ Toda, F; Tanaka, K; Koshiro, K (1991). "A New Preparative Method for Optically Active Diarylcarbinols". Tetrahedron: Asymmetry. 2: 873–874. doi:10.1016/s0957-4166(00)82198-9.
  11. ↑ Qin, J (2012). "Anti-Tumor Effects of Brucine Immune-Nanoparticles on Hepatocellular Carcinoma". International Journal of Nanomedicine. 7: 369–379.
  12. ↑ Serasanambati, M; Chilakapati, S; Vanagavaragu, J; Cilakapati, D (2014). "Inhibitory effect of gemcitabine and brucine on MDA MB-231 human breast cancer cells". International Journal of Drug Delivery. 6.
  13. ↑ Zhang, J; Wang, S; Chen, X; Zhide, H; Xiao, M (2003). "Capillary Electrophorese with Field-Enhanced Stacking for Rapid and Sensitive Determination of Strychnine and Brucine". Analytical and Bioanalytical Chemistry. 376: 210–213.
  14. ↑ Rathi, A; Srivastava, N; Khatoon, S; Rawat, A (2008). "TLC Determination of Strychnine and Brucine of Strychnos nun vomica in Ayurveda and Homeopathy Drugs". Chromatographia. 67: 607–613. doi:10.1365/s10337-008-0556-z.
  15. ↑ http://www.mgpingredients.com/product-list/SDA-40-2.html
  16. ↑ Dumas, Alexandre (1845). The Count of Monte Cristo. Feedbooks. p. 622.
  17. ↑ "Synopsis for The Mechanic". IMDb. Retrieved 30 April 2015.
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