Coniin

Structural formula
General
Surname	Coniin
other names	( S ) -2-propylpiperidine
Molecular formula	C 8 H 17 N [( S ) -Coniine] ; C 8 H 17 NHBr {( S ) -Coniine · hydrobromide } ; C 8 H 17 N.HCl {( S ) -Coniine · hydrochloride } ;
Brief description	colorless to yellow-greenish liquid
External identifiers / databases
EC number	207-282-6
ECHA InfoCard	100.006.621
PubChem	441072
ChemSpider	389878
Wikidata	Q421994
properties
Molar mass	127.23 g mol −1
Physical state	liquid
density	0.84-0.85 g cm -3
Melting point	−2 ° C ; 211 ° C {( S ) -coniine · hydrobromide} ; 221 ° C {( S ) -coniine hydrochloride} ;
boiling point	166-166.5 ° C {( S ) -coniine}
Vapor pressure	23 h Pa (61 ° C)
solubility	moderately in water (1 ml in 100 ml water); easily soluble in ethanol , diethyl ether ;
Refractive index	1.4512 (22 ° C)
safety instructions
H and P phrases	H: 226-301-311-331-351
	P: 261-280-301 + 310-311
Toxicological data	100 mg kg −1 ( LD 50 , mouse , oral ) ; 5 mg kg −1 ( LD 50 , rat , oral ) ; 6–7 mg kg −1 ( LD 50 , human , oral ) ; 19 mg kg −1 ( LD 50 , mouse , iv ) ; 3 mg kg −1 ( LD 50 , cat , iv ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Coniin is a pseudo-alkaloid that is derived from piperidine . It occurs in plants such as the spotted hemlock ( Conium maculatum ) and is neurotoxic . The best-known victim of the Coniins is the Greek philosopher Socrates , who was given a hemlock in 399 BC. Was executed.

Natural occurrence

The spotted hemlock ( Conium maculatum L.) smells penetratingly like 'mouse urine', this is caused by coniin, which is contained in all parts of the plant.

In addition to the spotted hemlock, coniin occurs in other plants such as dog parsley ( Aethusa cynapium ) and the yellow pitcher plant . All parts of the plants contain the toxin, but the seeds are particularly rich. The spotted hemlock contains between 1.5 and 2.0% piperidine alkaloids .

The Heidelberg pharmacist Philipp Lorenz Geiger is considered to be the discoverer of Coniin .

properties

Coniin is a clear, oily liquid with a burning pungent taste and odor of mouse urine. The substance quickly turns brown in air. Coniin dissolves little in water (1 ml in 100 ml water), but very well in ethanol and ether . The specific rotation [α] _D is + 15.7 °.

synthesis

In 1886 Albert Ladenburg succeeded in synthesizing coniin via a Knoevenagel condensation as the first synthesis of an alkaloid . 2-Picoline reacts with acetaldehyde in the presence of a base with elimination of water to form 2-propenylpyridine, which is hydrogenated to racemic coniine on a catalyst :

Coniin is no longer technically produced in this way today.

Biosynthesis of the conium alkaloids

Like N- methylconiine , conhydrin and pseudoconhydrin, coniin belongs to the group of conium alkaloids , all of which are found in the spotted hemlock. The piperidine derivatives are synthesized in the plant by first tetramerizing four C ₂ units to form a 3,5,7-trioxo- octanoic acid , reducing these and, after transamination, cyclizing them to give γ- conicein . The plant can produce all conium alkaloids from this raw material. A previously discussed biosynthetic pathway via lysine has now been refuted.

use

Coniin used to be used as a hydrobromide or hydrochloride as an external pain reliever in rubs. Due to the high toxicity of the substance, no medical uses are currently known. Other authors preferred coniin hydrobromide .

Safety instructions and toxicology

Coniin is well absorbed by the mucous membranes and the intact skin and develops a poisonous effect similar to nicotine and curare , whereby the motor nerves are initially excited but later paralyzed. Contact with the sap of the plant can cause skin irritation, accompanied by a burning sensation. Coniin can be recognized by its particularly characteristic, burning taste when ingested. In the throat and pharynx area , after ingestion, it causes irritation of the oral mucosa and increased salivation . Dizziness, shortness of breath, bronchial spasms, clouding of consciousness, visual disturbances and signs of paralysis are further symptoms. The lethal dose of the substance in adults is around 500 mg, which corresponds to six to seven milligrams per kilogram of body weight. Death occurs after 0.5 to 5 hours in full consciousness through paralysis of the chest muscles.

In contrast to the nicotine of tobacco , anatoxin A of some cyanobacteria , cytisine of the golden rain , epibatidine of the poison dart frogs and arecoline of the betel nuts, coniin has an antagonistic effect on the acetylcholine receptors, similar to scopolamine , which occurs in nightshade plants such as the mandrake or thorn apple.

Coniin also has an anesthetic effect on insects ; in the secretion of the nectaries of the (carnivorous) yellow pitcher plant , it helps the plant catch prey.

Web links

Bernhard Peter. Death potion of antiquity: the hemlock and the coniin

Individual evidence

↑ ^a ^b ^c data sheet (±) -Coniine from Sigma-Aldrich , accessed on August 12, 2012 ( PDF ).
↑ ^a ^b ^c Entry on Coniin in the GESTIS substance database of the IFA , accessed on October 9, 2007(JavaScript required) .
^ ^A ^b ^c The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; P. 421, ISBN 978-0-911910-00-1 .
↑ ^a ^b ^c H. PT Ammon: Hunnius Pharmaceutical Dictionary . de Gruyter, 2004, ISBN 3-11-017487-1 .
↑ David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Physical Constants of Organic Compounds, pp. 3-446.
↑ ^a ^b Entry on Coniin in the ChemIDplus database of the United States National Library of Medicine (NLM) .
^ WR Carlile: Pesticide Selectivity, Health and the Environment. P. 259, Cambridge University Press, 2006, ISBN 978-0-521-81194-1 .
↑ ^a ^b K. Aktories, U. Förstermann, FB Hofmann: General and special pharmacology and toxicology. 9th edition, p. 1076, Elsevier, Urban & Fischer, 2006, ISBN 978-3-437-44490-6 .
^ Proceedings of the Society for Experimental Biology and Medicine. Vol. 35, p. 316, 1936.
^ Albert Gossauer: Structure and reactivity of biomolecules , Verlag Helvetica Chimica Acta, Zurich, 2006, p. 424, ISBN 978-3-906390-29-1 .
^ Geiger, Philipp Lorenz. In: Edward Kremers, George Urdang, Glenn Sonnedecker: Kremers and Urdang's History of Pharmacy. American Institute of the History of Pharmacy, Madison WI 1986, ISBN 0-931292-17-4 , p. 459.
↑ ^a ^b M. Hesse: Alkaloide , Helvetica Chimica Acta, 2000, ISBN 3-906390-19-5 .
^ Albert Ladenburg: Synthesis of the active Coniine , Reports of the German Chemical Society 19 (1886), pp. 2578-2583, doi : 10.1002 / cber.188601902215 .
↑ E. Glotter, L. Zechmeister: Advances in the chemistry of organic natural substances . Springer, 1971, ISBN 3-211-81024-2 .
^ Gerhard Madaus: Textbook of biological remedies. Volume II. Olms, Hildesheim / New York 1979, ISBN 3-487-05891-X , p. 1082 (reprint of the Leipzig 1938 edition).

[Sigma-1] ta sheet (±) -Coniine from Sigma-Aldrich , accessed on August 12, 2012 ( PDF ).

[GESTIS-2] Entry on Coniin in the GESTIS substance database of the IFA , accessed on October 9, 2007(JavaScript required) .

[MERCK_Index-3] A ^b ^c The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; P. 421, ISBN 978-0-911910-00-1 .

[Hunnius-4] H. PT Ammon: Hunnius Pharmaceutical Dictionary . de Gruyter, 2004, ISBN 3-11-017487-1 .

[CRC-5] David R. Lide (Ed.): CRC Handbook of Chemistry and Physics . 90th edition. (Internet version: 2010), CRC Press / Taylor and Francis, Boca Raton, FL, Physical Constants of Organic Compounds, pp. 3-446.

[ChemIDplus-6] Entry on Coniin in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[7] WR Carlile: Pesticide Selectivity, Health and the Environment. P. 259, Cambridge University Press, 2006, ISBN 978-0-521-81194-1 .

[aspt-8] K. Aktories, U. Förstermann, FB Hofmann: General and special pharmacology and toxicology. 9th edition, p. 1076, Elsevier, Urban & Fischer, 2006, ISBN 978-3-437-44490-6 .

[9] Proceedings of the Society for Experimental Biology and Medicine. Vol. 35, p. 316, 1936.

[Gossauer-10] Albert Gossauer: Structure and reactivity of biomolecules , Verlag Helvetica Chimica Acta, Zurich, 2006, p. 424, ISBN 978-3-906390-29-1 .

[Geiger-11] Geiger, Philipp Lorenz. In: Edward Kremers, George Urdang, Glenn Sonnedecker: Kremers and Urdang's History of Pharmacy. American Institute of the History of Pharmacy, Madison WI 1986, ISBN 0-931292-17-4 , p. 459.

[Hesse-12] M. Hesse: Alkaloide , Helvetica Chimica Acta, 2000, ISBN 3-906390-19-5 .

[Ladenburg-13] Albert Ladenburg: Synthesis of the active Coniine , Reports of the German Chemical Society 19 (1886), pp. 2578-2583, doi : 10.1002 / cber.188601902215 .

[Glotter-14] E. Glotter, L. Zechmeister: Advances in the chemistry of organic natural substances . Springer, 1971, ISBN 3-211-81024-2 .

[15] Gerhard Madaus: Textbook of biological remedies. Volume II. Olms, Hildesheim / New York 1979, ISBN 3-487-05891-X , p. 1082 (reprint of the Leipzig 1938 edition).