Glaucine

Structural formula
Basic structural formula (stereocenter is marked with an * )
General
Surname	Glaucine
other names	1,2,9,10-tetramethoxyaporphine Bromcholite Boldine dimethyl ether Glauvent 5,6,6a, 7-tetrahydro-1,2,9,10-tetramethoxy-6-methyl-4 H -dibenzo [ de , g ] quinoline
Molecular formula	C 21 H 25 NO 4
Brief description	bitter taste
External identifiers / databases
CAS number 475-81-0 ( S ) 38325-02-9 ( R ) 5630-11-5 (±) EC number 207-501-5 ECHA InfoCard 100.006.820 PubChem 16754 ChemSpider 15883 Wikidata Q2398298
properties
Molar mass	355.43 g mol −1
Physical state	firmly
density	1.14 g cm 3
Melting point	120-125 ° C
solubility	soluble in acetone , ethanol , chloroform , ethyl acetate insoluble in water, benzene and hexane
safety instructions
GHS hazard labeling no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Glaucine is an alkaloid from the group of aporphine alkaloids . It is widespread in the plant kingdom and can be found, for example, in the yellow horn poppy ( Glaucium flavum ). It is used as a cough remedy, among other things.

In the case of the alkaloids, it is a common practice to derive the name from the plant in which it was first discovered, hence Glaucin is derived from "Glaucium".

Occurrence

Yellow horn poppy ( Glaucium flavum)

In addition to the resources in the Yellow horned poppy ( Glaucium flavum ), one finds Glaucium also in Annonengewächsen ( Annonaceae ), Berberitzengewächsen ( Berberidaceae ), euphorbia ( Euphorbiaceae ), Erdrauchgewächsen ( Fumarioideae ), laurel family ( Lauraceae ), magnolia family ( Magnoliaceae ), poppy plants ( Papaveraceae ) and buckthorn family ( Rhamnaceae ). Many of these plants are common in Europe, Asia and South America.

Stereoisomerism

Glaucin is chiral, there are two stereoisomers, but in nature i. d. Usually only the ( S ) -configured form is available. The ( R ) -configured glaucin can be produced synthetically from ( S ) -glaucin. The two stereoisomers are designated as follows:

• ( S ) -5,6,6a, 7-tetrahydro-1,2,9,10-tetramethoxy-6-methyl-4 H -dibenzo [ de , g ] quinoline
• ( R ) -5,6,6a, 7-tetrahydro-1,2,9,10-tetramethoxy-6-methyl-4 H -dibenzo [ de , g ] quinoline

Glaucine (2 stereoisomers)
( S ) configuration	( R ) configuration

biosynthesis

In the poppy family ( Papaveraceae ) glaucin 3 and corydin usually occur together because the biosynthesis from norlaudanosolin 1 does not differ from norprotosinomenin 2 . From the norprotosinomenin onwards, the CC bond either rotates or not, this influences the position of the substituents on the ring and decides whether glaucin or corydin is formed. Schematic representation:

synthesis

The first synthetically produced aporphine alkaloid is glaucine. The synthesis was developed by Robert Pschorr and Johannes Gadamer using papaverine as the starting material:

First, in the synthesis, papaverine 1 is nitrated using nitric acid at low temperatures and converted into nitropapaverine 2 . This is then methylated by dimethyl sulfate on the heterocyclic ring and this is how 3 is formed . The nitro group is reduced with tin and hydrochloric acid and the r-aminolaudanosine 4 is formed , which is mixed with sodium nitrite in acidic solution to form the diazo compound 5 . In the last step, copper powder is added to the diazo compound and the ring closure to form glaucine 6 takes place with visible evolution of nitrogen gas :

use

Glaucin has a wide range of pharmacological effects, for example it can have anti-inflammatory effects, but it can also cause cramps, loss of consciousness or respiratory paralysis.

As an antitussive (remedy for coughs) it is used in Bulgaria and other countries and has a similar effect to codeine , but it is said to have a longer duration of action. It is characterized by the fact that the central respiratory center is not suppressed and glaucin is not addictive with prolonged use.

Glaucin is also rarely used as a narcotic drug, with effects such as hallucinations, tiredness, vomiting, dizziness and decreased blood pressure.

The derivative of the glaucine dehydroglaucine has an antibacterial effect.

Glaucin also acts as a fungicide .

literature

• Falbe J., Regitz M .: Römpp Lexicon - Chemistry . Edition 10, Thieme, Stuttgart 1997 , ISBN 3-13-734710-6
• Cordell Geoffrey A .: Introduction to Alkaloids: A Biogenetic Approach . John Wiley & Sons Inc., Canada 1981 , ISBN 0-471-03478-9

Individual evidence

1. ^ KH Bauer: Handbuch der Chemie. With regard to pharmacy . Volume 2. Publishing bookstore by CF Winter, Heidelberg 1843 , pp. 1200–1202.
2. ^ ^{A b} Ian W. Southon, John Buckingham: Dictionary of Alkaloids, Second Edition with CD-ROM . CRC Press, 1989, ISBN 978-0-412-24910-5 , pp. 466 ( limited preview in Google Book search).
3. ^ Carl L. Yaws: Thermophysical Properties of Chemicals and Hydrocarbons . William Andrew, 2014, ISBN 978-0-323-29060-9 , pp. 341 ( limited preview in Google Book search).
4. ↑ ^{a b} entry on glaucin. In: Römpp Online . Georg Thieme Verlag, accessed on October 1, 2017 .
5. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
6. ↑ KH Bauer: The current state of the synthesis of plant alkaloids . Springer Fachmedien, Wiesbaden 1913 , pp. 126–129; ISBN 978-3-322-98170-7 .
7. ↑ J. Ap Simon: the total synthesis of natural products . Wiley Online Library, London 1977 , pp. 80-81, 121-129, doi: 10.1002 / 9780470129647 .
8. ^ ^{A b} G. MJ Meyer, MR Meyer, DK Wissbach, HH Maurer: Studies on the metabolism and toxicological detection of glaucine, an isoquinoline alkaloid from Glaucium flavum (Papaveraceae), in rat urine using GC-MS, LC-MS ⁿ and LC-high-resolution MS ⁿ , in: wiley online library , 2013 , 48 (1), pp. 24-41; doi: 10.1002 / jms.3112 .