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{{Short description|Poisonous alkaloid similar to strychnine}} |
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{{Distinguish|Brucite}} |
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{{chembox |
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{{chembox |
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| Watchedfields = changed |
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| verifiedrevid = 451262997 |
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| verifiedrevid = 459984884 |
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|ImageFile=brucine.svg |
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| ImageFile=Brucine2.svg |
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|ImageSize=200px |
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| ImageSize=200px |
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|IUPACName=2,​3-​dimethoxystrychnidin-​10-​one |
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| IUPACName=2,3-Dimethoxystrychnidin-10-one |
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|OtherNames=2,3-Dimethoxystrychnine<br>10,11-Dimethoxystrychnine |
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| SystematicName=(4b''R'',4b<sup>1</sup>''S'',7a''S'',8a''R'',8a<sup>1</sup>''R'',12a''S'')-2,3-Dimethoxy-4b<sup>1</sup>,5,6,7a,8,8a,8a<sup>1</sup>,11,12a,13-decahydro-14''H''-12-oxa-7,14a-diaza-7,9-methanocycloheptacyclopentafluoranthen-14-one |
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|Section1= {{Chembox Identifiers |
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| OtherNames=2,3-Dimethoxystrychnine<br>10,11-Dimethoxystrychnine |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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|Section1={{Chembox Identifiers |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 390579 |
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| ChemSpiderID = 390579 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo=357-57-3 |
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| CASNo=357-57-3 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 501756 |
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| ChEMBL = 501756 |
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| PubChem=442021 |
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| PubChem=442021 |
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| IUPHAR_ligand = 342 |
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| IUPHAR_ligand = 342 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = C09084 |
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| KEGG = C09084 |
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| ChEBI = 3193 |
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| SMILES = O=C7N2c1cc(OC)c(OC)cc16423(OC/C=C5\3C6N(CC4)C5)C7 |
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| RTECS = EH8925000 |
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| UNNumber = 1570 |
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| EC_number = 206-614-7 |
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| SMILES = O=C7N2c1cc(OC)c(OC)cc16423(OC/C=C5\3C6N(CC4)C5)C7 |
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}} |
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|Section2= {{Chembox Properties |
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|Section2={{Chembox Properties |
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|C=23|H=26|N=2|O=4 |
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| C=23 | H=26 | N=2 | O=4 |
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| Appearance= |
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| Density= |
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| Density= |
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| MeltingPtC=178 |
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|Section3= {{Chembox Hazards |
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|Section3={{Chembox Hazards |
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| GHSPictograms = {{GHS06}} |
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| MainHazards= |
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| GHSSignalWord = Danger |
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| FlashPt= |
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| HPhrases = {{H-phrases|300|330|412}} |
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| Autoignition= |
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| PPhrases = {{P-phrases|260|264|270|271|273|284|301+310|304+340|310|320|321|330|403+233|405|501}} |
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| MainHazards= |
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| FlashPt= |
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'''Brucine''' is a bitter ] closely related to ]. It occurs in several plant species, the most well known being the '']'' tree, found in South-East Asia. |
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'''Brucine''' is an ] closely related to ], most commonly found in the '']'' tree. Brucine poisoning is rare, since it is usually ingested with strychnine, and strychnine is more ] than brucine. In ], it can be used as a tool for ]. |
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Brucine's name derives from this of the genus '']'', named after ] who brought back ''Brucea antidysenterica'' from Ethiopia. |
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While brucine is related to strychnine, it is not as poisonous. Nevertheless, a human consuming over 2 mg of pure brucine will almost certainly suffer symptoms resembling strychnine poisoning ({{LD50}} (rats, oral) 1 mg/kg, LD<sub>50</sub> (rabbit, oral) 4 mg/kg).{{Citation needed|date=September 2011}} The probable fatal dose in adults is estimated at 1 gram.<ref>Gosselin, 1984{{clarify|date=January 2011}}</ref><ref>Arlina Borges, International Programme on Chemical Safety (IPCS), Canadian Centre for Occupational Health and Safety (CCOHS), April 1990.</ref> |
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== History == |
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For medicinal purposes, brucine is primarily used in the regulation of high blood pressure and other comparatively benign cardiac ailments. It is cultivated commercially in some parts of the United States and European Union. |
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Brucine was discovered in 1819 by the French chemist ] and the French pharmacist ] in the ] of the ''Strychnos nux-vomica'' tree.<ref>{{cite book|last1=Wormley|first1=T|title=Micro-chemistry of poisons including their physiological, pathological, and legal relations: Adapted to the use of the medical jurist, physician, and general chemist.|url=https://archive.org/details/microchemis01worm|date=1869|publisher=W. Wood|location=New York}}</ref> While its ] 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.<ref>{{cite book|last1=Buckingham|first1=J|title=Bitter Nemesis: The Intimate History of Strychnine|date=2007|publisher=CRC Press|page=225}}</ref> |
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== Identification == |
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The alkaloid brucine is isostructural to ], with methoxy groups at the aromatic ring rather than hydrogens (positions 9 and 10). Both brucine and strychnine are commonly used as agents for ]. The separation of racemic mixtures by alkaloids from the cinchona bark has been known since 1853, when its use as such was reported by Pasteur. The ability of brucine, and to a lesser extent strychnine, to function as resolving agents for amino acids was reported by Fisher in 1899. Brucine and strychnine are ] and thus have a tendency to crystallize with acids. The acid-base reaction leaves the brucine protonated at the N(2) position. The formation of ]ic salts has been reported for thousands of organic compounds. The packing of brucine in corrugated (waving) layers was an essential aspect in the co-crystallization of brucine, whereas strychnine was shown to crystallize predominantly in bilayers. |
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Brucine can be detected and quantified using ].<ref>{{cite journal|last1=Teske|first1=J|last2=Weller|first2=J|last3=Albrecht|first3=U|last4=Fieguth|first4=A|title=Fatal Intoxication Due to Brucine|journal=Journal of Analytical Toxicology|date=2011|volume=35|issue=4|pages=248–253|doi=10.1093/anatox/35.4.248|pmid=21513620|doi-access=free}}</ref> Historically, brucine was distinguished from strychnine by its reactivity toward ].<ref>{{cite book|last1=Glasby|first1=J.|title=Encyclopedia of the alkaloids|url=https://archive.org/details/encyclopediaofal0000glas|url-access=registration|date=1975|publisher=Plenum Press|location=New York|page=214|isbn=9780306308451}}</ref> |
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== Applications == |
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==Cultural references== |
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Perhaps the best-known reference to brucine occurs in '']'', the novel by French author ], in a discussion of ]: |
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:''"Well", replied Monte Cristo, "suppose, then, that this poison was brucine, and you were to take a milligramme the first day, two milligrammes the second day, and so on."'' |
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=== Chemical applications === |
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Brucine was also mentioned in the 1972 movie '']'', starring ] in which the young ] Steve McKenna (]) betrays his mentor, aging hitman Arthur Bishop (Bronson), using a celebratory glass of wine spiked with brucine, leaving Bishop to die of an apparent heart attack. |
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Since brucine is a large ] molecule, it has been used in ]. Fisher first reported its use as a resolving agent in 1899, and it was the first natural product used as an ] in a reaction resulting in an ] enrichment by ], in 1904.<ref>{{cite book|last1=Koskinen|first1=A|title=Asymmetric synthesis of natural products|url=https://archive.org/details/asymmetricsynthe0000kosk|url-access=registration|date=1993|publisher=J. Wiley|location=Chichester|pages=, 28–29}}</ref> Its bromide salt has been used as the ] in ] to selectively bind one of two an]ic enantiomers.<ref>{{cite journal|last1=Zarbua|first1=K|last2=Kral|first2=V|title=Quaternized brucine as a novel chiral selector|journal=Tetrahedron: Asymmetry|year=2002|pages=2567–2570|doi=10.1016/s0957-4166(02)00715-2|volume=13|issue=23}}</ref> Brucine has also been used for ] in ] to resolve dihydroxy ],<ref>{{cite journal|last1=Malkar|first1=N|last2=Kumar|first2=V|title=Optical resolution of (±)-Threo-9,10,16-trihydroxy hexadecanoic acid using (−)brucine|journal=Journal of the American Oil Chemists' Society|date=1998|volume=75|issue=10|pages=1461–1463|doi=10.1007/s11746-998-0202-9|s2cid=83662051}}</ref> as well as di]]s.<ref>{{cite journal|last1=Toda|first1=F|last2=Tanaka|first2=K|last3=Koshiro|first3=K|title=A New Preparative Method for Optically Active Diarylcarbinols|journal=Tetrahedron: Asymmetry|date=1991|volume=2|issue=9|pages=873–874|doi=10.1016/s0957-4166(00)82198-9}}</ref> |
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=== Medical applications === |
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==References== |
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While brucine has been shown to have good ] effects, on both ]<ref>{{cite journal|last1=Qin|first1=J|title=Anti-Tumor Effects of Brucine Immune-Nanoparticles on Hepatocellular Carcinoma|journal=International Journal of Nanomedicine|date=2012|volume=7|pages=369–379|doi=10.2147/IJN.S27226|pmid=22334771|pmc=3273973|doi-access=free}}</ref> and ],<ref>{{cite journal|last1=Serasanambati|first1=M|last2=Chilakapati|first2=S|last3=Vanagavaragu|first3=J|last4=Cilakapati|first4=D|title=Inhibitory effect of gemcitabine and brucine on MDA MB-231 human breast cancer cells|journal=International Journal of Drug Delivery|date=2014|volume=6|url=http://www.arjournals.org/index.php/ijdd/article/view/1422|access-date=2015-05-02|archive-date=2016-03-04|archive-url=https://web.archive.org/web/20160304035757/http://www.arjournals.org/index.php/ijdd/article/view/1422|url-status=dead}}</ref> its narrow ] has limited its use as a treatment for ]. |
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{{refimprove|date=January 2011}} |
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Brucine is also used in ] as an ] and ] agent,<ref>{{cite journal|last1=Zhang|first1=J|last2=Wang|first2=S|last3=Chen|first3=X|last4=Zhide|first4=H|last5=Xiao|first5=M|title=Capillary Electrophorese with Field-Enhanced Stacking for Rapid and Sensitive Determination of Strychnine and Brucine|journal=Analytical and Bioanalytical Chemistry|date=2003|volume=376|issue=2|pages=210–213|doi=10.1007/s00216-003-1852-y|pmid=12692702|s2cid=7832819}}</ref> as well as in some ] and ] drugs.<ref>{{cite journal|last1=Rathi|first1=A|last2=Srivastava|first2=N|last3=Khatoon|first3=S|last4=Rawat|first4=A|title=TLC Determination of Strychnine and Brucine of Strychnos nun vomica in Ayurveda and Homeopathy Drugs|journal=Chromatographia|date=2008|pages=607–613|doi=10.1365/s10337-008-0556-z|volume=67|issue=7–8|s2cid=94626190}}</ref> |
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=== Alcohol denaturant === |
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Brucine is one of the many chemicals used as a ] to make ] unfit for human consumption.<ref name = "cornell">{{cite web |url= https://www.law.cornell.edu/cfr/text/27/21.151|title= List of denaturants authorized for denatured spirits|date=30 August 2016|website= www.law.cornell.edu|publisher= Cornell Law School|access-date= 2019-08-24}}</ref> |
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== Cultural references == |
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One of the most famous cultural references to brucine occurs in '']'', the novel by French author ]. In a discussion of ], Monte Cristo states: |
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“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.”<ref>{{cite book|last1=Dumas|first1=Alexandre|title=The Count of Monte Cristo|date=1845|publisher=Feedbooks|page=622}}</ref> |
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Brucine is also mentioned in the 1972 version of '']'', 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.<ref>{{cite web|title=Synopsis for The Mechanic|url=https://www.imdb.com/title/tt0068931/synopsis?ref_=ttpl_pl_syn|website=IMDb|access-date=30 April 2015}}</ref> |
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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 ] occurs at 69 % greater ]. A drink laden with brucine, overwhelmingly bitter at far below ], would cause an intended victim to gag on the first sip. |
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== Safety == |
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Brucine intoxication occurs very rarely, since it is usually ingested with strychnine. Symptoms of brucine intoxication include muscle ]s, ]s, ], and ]. Brucine’s mechanism of action closely resembles that of ]. It acts as an ] at ]s and paralyzes ]. |
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The probable ] of brucine in adults is 1 g.<ref>{{cite book|last1=Gosselin|first1=R. E.|last2=Smith|first2=R. P.|last3=Hodge|first3=H. C.|title=Clinical Toxicology of Commercial Products|date=1984|publisher=Williams & Wilkins|location=Baltimore/London|edition=5}}</ref> In other animals, the ] varies considerably. |
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{| class="wikitable" |
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! Animal !! Route of entry !! LD<sub>50</sub><ref>{{cite web | url = https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~W5wHBo:2 | title = Brucine | website = Toxnet | publisher = NIH | access-date = 2018-10-07}}</ref> |
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| Mouse || ] || 60 mg/kg |
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| Rat || ] || 91 mg/kg |
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| Rabbit || ] || 4 mg/kg |
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] |
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== References == |
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{{Reflist}} |
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{{Reflist}} |
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==External links== |
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== External links == |
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{{Wikisource1911Enc|Brucine}} |
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{{Wikisource1911Enc|Brucine}} |
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* , INCHEM.org |
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* , inchem.org |
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{{Glycinergics}} |
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{{Glycinergics}} |
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{{Authority control}} |
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