Brucine

Short description: Poisonous alkaloid similar to strychnine

Brucine

Names
IUPAC name

2,3-Dimethoxystrychnidin-10-one

Systematic IUPAC name

(4bR,4b1S,7aS,8aR,8a1R,12aS)-2,3-Dimethoxy-4b1,5,6,7a,8,8a,8a1,11,12a,13-decahydro-14H-12-oxa-7,14a-diaza-7,9-methanocyclohepta[cd]cyclopenta[g]fluoranthen-14-one

Other names

2,3-Dimethoxystrychnine
10,11-Dimethoxystrychnine

Identifiers

CAS Number

* 357-57-3 Y

3D model (JSmol)

* Interactive image

ChEBI |

* CHEBI:3193

ChEMBL |

* ChEMBL501756 Y

ChemSpider |

* 390579 Y

EC Number |

* 206-614-7

IUPHAR/BPS

* 342

KEGG |

* C09084 Y

PubChem CID

* 442021

RTECS number |

* EH8925000

UNII |

* 6NG17YCK6H Y

UN number | 1570

InChI

* InChI=1S/C23H26N2O4/c1-27-16-8-14-15(9-17(16)28-2)25-20(26)10-18-21-13-7-19-23(14,22(21)25)4-5-24(19)11-12(13)3-6-29-18/h3,8-9,13,18-19,21-22H,4-7,10-11H2,1-2H3/t13-,18-,19-,21-,22-,23+/m0/s1 Y

Key: RRKTZKIUPZVBMF-IBTVXLQLSA-N Y

* InChI=1/C23H26N2O4/c1-27-16-8-14-15(9-17(16)28-2)25-20(26)10-18-21-13-7-19-23(14,22(21)25)4-5-24(19)11-12(13)3-6-29-18/h3,8-9,13,18-19,21-22H,4-7,10-11H2,1-2H3/t13-,18-,19-,21-,22-,23+/m0/s1

Key: RRKTZKIUPZVBMF-IBTVXLQLBR

SMILES

* O=C7N2c1cc(OC)c(OC)cc1[C@@]64[C@@H]2[C@@H]3[C@@H](OC/C=C5\\[C@@H]3C[C@@H]6N(CC4)C5)C7

Properties

Chemical formula

| C23H26N2O4
Molar mass | 394.471 g·mol−1
Melting point |  178 °C (352 °F; 451 K)
Hazards
GHS pictograms |
GHS Signal word | Danger

GHS hazard statements

| H300, H330, H412

GHS precautionary statements

| P260, P264, P270, P271, P273, P284, P301+310, P304+340, P310, P320, P321, P330, P403+233, P405, P501

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Y verify (what is YN ?)
Infobox references

Tracking categories (test):

* SizeSet

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 synthetic chemistry, it can be used as a tool for stereospecific chemical syntheses.

Brucine is named from the genus Brucea, named after James Bruce who brought back Brucea antidysenterica from Ethiopia.

## Contents

* 1 History
* 2 Identification
* 3 Applications
* 3.1 Chemical applications
* 3.2 Medical applications
* 3.3 Alcohol denaturant
* 4 Cultural references
* 5 Safety
* 6 References
* 7 External links

## History

Brucine was 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]

## Identification

Brucine can be detected and quantified using liquid chromatography-mass spectrometry.[3] Historically, brucine was distinguished from strychnine by its reactivity toward chromic acid.[4]

## 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.[5] Its bromide salt has been used as the stationary phase in HPLC in order to selectively bind one of two anionic enantiomers.[6] Brucine has also been used in fractional distillation in acetone in order to resolve dihydroxy fatty acids,[7] as well as diarylcarbinols.[8]

### Medical applications

While brucine has been shown to have good anti-tumor effects, on both hepatocellular carcinoma[9] and breast cancer,[10] 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,[11] as well as in some Ayurveda and homeopathy drugs.[12]

### Alcohol denaturant

Brucine is one of the many chemicals used as a denaturant to make alcohol unfit for human consumption.[13]

## 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.”[14]

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.[15]

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 fatal dose of brucine in adults is 1 g.[16] In other animals, the LD50 varies considerably.

Animal | Route of Entry | LD50[17]

|
|

Mouse | Subcutaneous | 60 mg/kg
Rat | Intraperitoneal | 91 mg/kg
Rabbit | Oral | 4 mg/kg
Brucine's Mechanism of Action

## 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. https://archive.org/details/microchemis01worm.
2. ↑ Buckingham, J (2007). Bitter Nemesis: The Intimate History of Strychnine. CRC Press. p. 225.
3. ↑ Teske, J; Weller, J; Albrecht, U; Fieguth, A (2011). "Fatal Intoxication Due to Brucine". Journal of Analytical Toxicology 35 (4): 248–253. doi:10.1093/anatox/35.4.248. PMID 21513620.
4. ↑ Glasby, J. (1975). Encyclopedia of the alkaloids. New York: Plenum Press. p. 214. ISBN 9780306308451. https://archive.org/details/encyclopediaofal0000glas.
5. ↑ Koskinen, A (1993). Asymmetric synthesis of natural products. Chichester: J. Wiley. pp. 17, 28–29. https://archive.org/details/asymmetricsynthe0000kosk.
6. ↑ Zarbua, K; Kral, V (2002). "Quaternized brucine as a novel chiral selector". Tetrahedron: Asymmetry 13 (23): 2567–2570. doi:10.1016/s0957-4166(02)00715-2.
7. ↑ 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.
8. ↑ Toda, F; Tanaka, K; Koshiro, K (1991). "A New Preparative Method for Optically Active Diarylcarbinols". Tetrahedron: Asymmetry 2 (9): 873–874. doi:10.1016/s0957-4166(00)82198-9.
9. ↑ Qin, J (2012). "Anti-Tumor Effects of Brucine Immune-Nanoparticles on Hepatocellular Carcinoma". International Journal of Nanomedicine 7: 369–379. doi:10.2147/IJN.S27226. PMID 22334771.
10. ↑ 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. http://www.arjournals.org/index.php/ijdd/article/view/1422.
11. ↑ 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 (2): 210–213. doi:10.1007/s00216-003-1852-y. PMID 12692702.
12. ↑ 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 (7–8): 607–613. doi:10.1365/s10337-008-0556-z.
13. ↑ "List of denaturants authorized for denatured spirits". Cornell Law School. 30 August 2016. https://www.law.cornell.edu/cfr/text/27/21.151.
14. ↑ Dumas, Alexandre (1845). The Count of Monte Cristo. Feedbooks. p. 622.
15. ↑ "Synopsis for The Mechanic". https://www.imdb.com/title/tt0068931/synopsis?ref_=ttpl_pl_syn.
16. ↑ Gosselin, R. E.; Smith, R. P.; Hodge, H. C. (1984). Clinical Toxicology of Commercial Products (5 ed.). Baltimore/London: Williams & Wilkins.
17. ↑ "Brucine". NIH. https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~W5wHBo:2.

## External links

* Brucine, INCHEM.org

* v
* t
* e

Glycine receptor modulators

Receptor
(ligands)|

| GlyR|

* Agonists: β-Alanine
* β-ABA (BABA)
* β-AIBA
* Caesium
* D-Alanine
* D-Serine
* GABA
* Glycine
* Hypotaurine
* Ivermectin
* L-Alanine
* L-Proline
* L-Serine
* L-Threonine
* MDL-27531
* Milacemide
* Picolinic acid
* Propofol
* Quisqualamine
* Sarcosine
* Taurine

* Positive modulators: Alcohols (e.g., brometone, chlorobutanol (chloretone), ethanol (alcohol), tert-butanol (2M2P), tribromoethanol, trichloroethanol, trifluoroethanol)
* Alkylbenzene sulfonate
* Anandamide
* Barbiturates (e.g., pentobarbital, sodium thiopental)
* Chlormethiazole
* D12-116
* Dihydropyridines (e.g., nicardipine)
* Etomidate
* Ginseng constituents (e.g., ginsenosides (e.g., ginsenoside-Rf))
* Glutamic acid (glutamate)
* Ivermectin
* Ketamine
* Neuroactive steroids (e.g., alfaxolone, pregnenolone (eltanolone), pregnenolone acetate, minaxolone, ORG-20599)
* Nitrous oxide
* Penicillin G
* Propofol
* Tamoxifen
* Tetrahydrocannabinol
* Triclofos
* Tropeines (e.g., atropine, bemesetron, cocaine, LY-278584, tropisetron, zatosetron)
* Volatiles/gases (e.g., chloral hydrate, chloroform, desflurane, diethyl ether (ether), enflurane, halothane, isoflurane, methoxyflurane, sevoflurane, toluene, trichloroethane (methyl chloroform), trichloroethylene)
* Xenon
* Zinc

* Antagonists: 2-Aminostrychnine
* 2-Nitrostrychnine
* 4-Phenyl-4-formyl-N-methylpiperidine
* αEMBTL
* Bicuculline
* Brucine
* Cacotheline
* Caffeine
* Colchicine
* Colubrine
* Cyanotriphenylborate
* Dendrobine
* Diaboline
* Endocannabinoids (e.g., 2-AG, anandamide (AEA))
* Gaboxadol (THIP)
* Gelsemine
* iso-THAZ
* Isobutyric acid
* Isonipecotic acid
* Isostrychnine
* Laudanosine
* N-Methylbicuculline
* N-Methylstrychnine
* N,N-Dimethylmuscimol
* Nipecotic acid
* Pitrazepin
* Pseudostrychnine
* Quinolines (e.g., 4-hydroxyquinoline, 4-hydroxyquinoline-3-carboxylic acid, 5,7-CIQA, 7-CIQ, 7-TFQ, 7-TFQA)
* RU-5135
* Sinomenine
* Strychnine
* Thiocolchicoside
* Tutin

* Negative modulators: Amiloride
* Benzodiazepines (e.g., bromazepam, Chemistry:Clonazepam

|

NMDAR|

* See here instead.

Transporter
(blockers)|

| GlyT1|

* ACPPB
* ALX-1393
* ALX-5407 (NFPS)
* AMG-747
* ASP2535
* BIIB-104 (PF-04958242)
* Bitopertin (RG1678/RO4917838)
* CP-802079
* Ethanol (alcohol)
* Glycyldodecylamide
* GSK1018921
* LY-2365109
* ORG-24598
* ORG-25935 (SCH-900435)
* PF-02545920
* PF-03463275
* Sarcosine
* SSR-103,800
* SSR-504,734

|

GlyT2|

* Amoxapine
* Ethanol (alcohol)
* NAGly
* Opiranserin (VVZ-149)
* ORG-25543
* VVZ-368

See also
Receptor/signaling modulators
GABA receptor modulators
GABAA receptor positive modulators
Ionotropic glutamate receptor modulators

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Original source: https://en.wikipedia.org/wiki/Brucine. Read more

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Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Brucine&oldid=246570"
*[CID]: Compound ID
*[H300]: Fatal if swallowed
*[H330]: Fatal if inhaled
*[H412]: Harmful to aquatic life with long lasting effects
*[P260]: Do not breathe dust/fume/gas/mist/vapours/spray
*[P264]: Wash … thoroughly after handling
*[P270]: Do not eat, drink or smoke when using this product
*[P271]: Use only outdoors or in a well-ventilated area
*[P273]: Avoid release to the environment
*[P284]: Wear respiratory protection
*[P301+310]: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician
*[P304+340]: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
*[P310]: Immediately call a POISON CENTER or doctor/physician
*[P320]: Specific treatment is urgent (see … on this label)
*[P321]: Specific treatment (see … on this label)
*[P330]: Rinse mouth
*[P403+233]: Store in a well ventilated place. Keep container tightly closed
*[P405]: Store locked up
*[P501]: Dispose of contents/container to …
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[GlyR]: Glycine receptor
*[NMDAR]: N-Methyl-D-aspartate receptor
*[GlyT1]: Glycine transporter 1
*[GlyT2]: Glycine transporter 2