CH102143A - Method of rendering lobeline. - Google Patents
Method of rendering lobeline.Info
- Publication number
- CH102143A CH102143A CH102143DA CH102143A CH 102143 A CH102143 A CH 102143A CH 102143D A CH102143D A CH 102143DA CH 102143 A CH102143 A CH 102143A
- Authority
- CH
- Switzerland
- Prior art keywords
- lobeline
- anthraquinone
- acid
- therapeutically valuable
- alcohol
- Prior art date
Links
- MXYUKLILVYORSK-UHFFFAOYSA-N (+/-)-allo-lobeline Natural products C1CCC(CC(=O)C=2C=CC=CC=2)N(C)C1CC(O)C1=CC=CC=C1 MXYUKLILVYORSK-UHFFFAOYSA-N 0.000 title claims description 23
- MXYUKLILVYORSK-HBMCJLEFSA-N (-)-lobeline Chemical compound C1([C@@H](O)C[C@H]2N([C@H](CCC2)CC(=O)C=2C=CC=CC=2)C)=CC=CC=C1 MXYUKLILVYORSK-HBMCJLEFSA-N 0.000 title claims description 23
- 229930013610 lobeline Natural products 0.000 title claims description 21
- 229960002339 lobeline Drugs 0.000 title claims description 21
- 238000000034 method Methods 0.000 title claims description 10
- 238000009877 rendering Methods 0.000 title description 2
- 239000002253 acid Substances 0.000 claims description 20
- 229930013930 alkaloid Natural products 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 11
- 241000208672 Lobelia Species 0.000 claims description 9
- 230000001476 alcoholic effect Effects 0.000 claims description 5
- 150000003797 alkaloid derivatives Chemical class 0.000 claims description 4
- 239000012458 free base Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 2
- 235000002639 sodium chloride Nutrition 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 5
- 241000968111 Lobelia inflata Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QNRATNLHPGXHMA-XZHTYLCXSA-N (r)-(6-ethoxyquinolin-4-yl)-[(2s,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]methanol;hydrochloride Chemical compound Cl.C([C@H]([C@H](C1)CC)C2)CN1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OCC)C=C21 QNRATNLHPGXHMA-XZHTYLCXSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- -1 B. the chlorohydrate Chemical class 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Darstellung von Lobelin. Die Alkaloide der Lobelia inflata bilden ein kompliziertes Gemisch mehrerer Basen, das gewöhnlich als honigartige Masse be schrieben wird und aus dem die einzelnen, physiologisch verschieden wirkenden Kom ponenten infolge ihrer ähnlichen physikali schen und chemischen Eigenschaften und ihrer Empfindlichkeit namentlich gegen wässerige Säuren nur umständlich und unter Verlusten isoliert werden konnten.
Es fehlte zum Bei spiel an einer Methode, um das therapeutisch wertvolle Lobelin, unter Umgehung von sauren wässerigen Lösungen, einfach durch die Bil dung eines charakteristischen schwerlöslichen Salzes von den Begleitalkaloiden glatt abzu trennen und so zur einheitlichen kristalli sierten Base und ihren gebräuchlichen Salzen zu gelangen.
Es wurde nun gefunden, dass es gelingt, mit Hilfe der Anthrachinon-ss-monosulfosäure das therapeutisch wertvolle Lobelin aus dem Gemisch mit seinen Begleitalkaloiden in Form eines schwerlöslichen, gut kristallisierenden und beständigen Salzes abzuscheiden, wäh rend die Salze der Begleitalkaloide infolge ihrer grösseren Löslichkeit unter den Versuchs bedingungen in Lösung bleiben.
Das Verfahren beruht also darauf, dass man zu einem Gemisch der Lobelia-Alkaloide Anthrachinon-p-monosulfosäure zusetzt, wobei das therapeutisch wertvolle Löbelin in Form des schwerlöslichen Salzes dieser Säure ab geschieden wird, worauf man nach erfolgter Filtration eine alkalische Substanz, z. B. Na tronlauge, zu dem anthraehinon-ss-monosulfo- sauren Lobelin hinzufügt und so die freie Base herstellt.
Man kann diese zum Beispiel dadurch gewinnen, indem man zum Beispiel das Salz in feingepulvertem Zustand in Wasser suspendiert, unter Zufügen von Ammoniak mit Äther oder Chloroform die freie Base aufnimmt und durch Einengen der Lösung das Lobelin zur Kristallisation bringt.
Die Abscheidung des therapeutisch wert vollen Lobelins in Form seines anthrachinon-p- monosulfosauren Salzes aus dem natürlichen Gemisch der Lobelia- Alkaloide wird vorteil haft dadurch bewirkt, dass man das Alka- loidgemisch in Alkohol löst,
das therapeutisch wertvolle Lobelin durch Zusatz einer alko- holischen Lösung der Anthrachinon-ss-mono- sulfosäure ausfällt und das ausgeschiedene Salz nach dem Abfiltrieren aus heissem Alkohol unikristallisiert. Man kann auch so verfah ren, dass man das aus ätherischer Lösung mit einer Säure- ausgefällte Gemisch der Salze der Lobelia-Alkaloide in Alkohol löst und daraus das therapeutisch wertvolle Lobelin durch Zusatz einer alkoholischen Lösung der Arrthrachirion-p-monosulfosäure kristallinisch abscheidet.
Man kann auch wie folgt ver fahren: Aus dem in einem mit Wasser nicht mischbaren organischen Solvens gelösten Lo- belia-Alkaloidgemisch kann man das therapeu tisch wertvolle Lobelin durch Schütteln mit einer wässerigen Lösung der Anthrachinon-p- rnonosulfosäure abscheiden und das ausgeschie dene und abfiltrierte anthrachinon-p-rnonosulfo- saure Lobelin aus Alkohol umkristallisieren.
Das bisher unbekannte, in diesem Ver fahren zur Alkaloidtrennung benützte anthra- chinon-@-monosulfosarire Lobelin kristallisiert aus Alkohol in hellkanariengelben, glänzenden, dünnen, rhombischen Blättchen oder Spiessen, es erweicht unter Braunfärbung oberhalb 2000 und schmilzt unter Zersetzung bei langsamem Erhitzen schon von 206'0 C (corr.) an. In der gälte ist es in Alkohol sehr schwer, bei Siedetemperatur in 150 Teilen löslich, in kaltem Wasser ist es beinahe unlöslich.
Es enthält 2,1 % Stickstoff und 5,0 % Schwefel. <I>Beispiel 1:
</I> Das aus 4,5 kg Lobelia inflata durch Ex traktion und Abtrennung von nicht basischen Begleitstoffen nach bekannter Methode ge wonnene klare, honigartige, zähe Alkaloid gemisch (18 g) wird in der fünffachen Menge Alkohol gelöst, filtriert und mit etwa dem halben Gewicht Anthrachinon-f-monosulfo- säure, welche in<B>15-20</B> ccm Alkohol gelöst sind, versetzt. Nach eintägigem Stehen werden 7,5 g des anthrachinori-p-monosrrlfosauren Lobelins in Form von hellgelben, dünnen, rhombischen Blättchen abgesaugt.
Die Ana lyse des schon in diesem Zustande analysen- reinen Produktes ergab für N : 2,17 % (0,4163 g gaben 6,45 ccm n/10 NHs nach Kjeldahl), für S : 5,07 % (0,2562 g gaben 0,0946 g BaSO.i nach Carius). Die Analyse des aus heissem Alkohol umkristallisierten Präparates ergab für N :
2,05 0/0 (0,2838 g gaben 4,14 ccrn n/10 NH3 nach Iyeldahl). Theorie für C-#3 H.29 0#-,N. S03 HCi4 H-#Oa für N : 2,19 %, für S : 5,01 0%.
Zur Darstellung des freien Lobelins aus dein anthrachinon-p-inonosulfosariren Salz sus pendiert man dieses in feingepulverter Form in Wasser und zerlegt es mit Ammoniak unter Ausschütteln der Base mit Äther. Beim Verdampfen des Äthers hinterbleibt das reine Lobelin als weisse kristalline Masse, die ohne weitere Reinigung auf geeignete Salze, z. B. das Chlorhydrat, auf bekannte Weise verar beitet werden kann.
Beispiel <I>2:</I> Die Rohbasen aus Lobelia inflata werden in etwa der fünfzigfachen Menge Äther gelöst und die Lösung durch Filtration geklärt. Hierauf wird gesättigte, ätherische Ogalsäure so lange zugesetzt, als eine Fällung entsteht. Die Basen des Gemisches werden so als Oxalate abgeschieden.
Man sammelt nun die Ausscheidung, löst sie in Alkohol, fällt daraus wie in Beispiel 1 das therapeutisch wertvolle Lobelin durch Zusatz einer alkoholischen Lö sung von Anthrachinon-ss-monosulfosäure in Form des kristallinischen Salzes dieser Säure aus und bereitet daraus auf bekannte Weise die freie Base und ihre für den therapeutischen Gebrauch geeigneten Salze.
Method of rendering lobeline. The alkaloids of Lobelia inflata form a complicated mixture of several bases, which is usually described as a honey-like mass, and from which the individual, physiologically different components, due to their similar physical and chemical properties and their sensitivity to aqueous acids, are difficult and difficult to make Losses could be isolated.
For example, there was a lack of a method to separate the therapeutically valuable lobeline smoothly from the accompanying alkaloids, bypassing acidic aqueous solutions, simply by forming a characteristic sparingly soluble salt, and thus to get to the uniform crystallized base and its common salts .
It has now been found that it is possible to use the anthraquinone-ss-monosulfonic acid to separate the therapeutically valuable lobeline from the mixture with its accompanying alkaloids in the form of a sparingly soluble, well-crystallizing and stable salt, while the salts of the accompanying alkaloids are less due to their greater solubility remain in solution under the experimental conditions.
The method is based on adding anthraquinone-p-monosulfonic acid to a mixture of the Lobelia alkaloids, the therapeutically valuable Löbelin being deposited in the form of the sparingly soluble salt of this acid, whereupon, after filtration, an alkaline substance, e.g. B. sodium hydroxide solution, to which the anthraehinone-SS-monosulfonic acid lobeline is added and the free base is thus produced.
This can be obtained, for example, by suspending the salt in a finely powdered state in water, adding ammonia with ether or chloroform to absorb the free base and concentrating the solution to crystallize the lobeline.
The deposition of the therapeutically valuable lobeline in the form of its anthraquinone-p-monosulfonic acid salt from the natural mixture of lobelia alkaloids is advantageously effected by dissolving the alkaloid mixture in alcohol,
the therapeutically valuable lobeline precipitates through the addition of an alcoholic solution of the anthraquinone-SS-monosulfonic acid and the excreted salt unicrystallizes after being filtered off from hot alcohol. One can also proceed in such a way that the mixture of the salts of the lobelia alkaloids precipitated from an ethereal solution with an acid is dissolved in alcohol and the therapeutically valuable lobeline is separated from it in crystalline form by adding an alcoholic solution of the arrthrachirion-p-monosulfonic acid.
One can also proceed as follows: The therapeutically valuable lobeline can be separated from the lobelia alkaloid mixture dissolved in a water-immiscible organic solvent by shaking it with an aqueous solution of the anthraquinone-p-monosulfonic acid and the excreted and filtered off Recrystallize anthraquinone-p-monosulfonic acid lobeline from alcohol.
The previously unknown anthraquinone - @ - monosulfosarire lobeline used in this process for separating alkalis crystallizes from alcohol in light canary-yellow, shiny, thin, rhombic leaflets or skewers, it softens with a brown color above 2000 and melts with decomposition when slowly heated from 206 '0 C (corr.). In the cold it is very difficult in alcohol, soluble in 150 parts at boiling temperature, and almost insoluble in cold water.
It contains 2.1% nitrogen and 5.0% sulfur. <I> Example 1:
</I> The clear, honey-like, viscous alkaloid mixture (18 g) obtained from 4.5 kg of Lobelia inflata by extraction and separation of non-basic accompanying substances using a known method is dissolved in five times the amount of alcohol, filtered and mixed with about half the weight of anthraquinone-f-monosulfonic acid, which is dissolved in 15-20 cc of alcohol. After standing for one day, 7.5 g of the anthraquinori-p-monosrrlfosauren lobeline in the form of light yellow, thin, rhombic leaflets are sucked off.
The analysis of the analytically pure product already in this state showed for N: 2.17% (0.4163 g gave 6.45 ccm n / 10 NHs according to Kjeldahl), for S: 5.07% (0.2562 g gave 0.0946 g BaSO.i according to Carius). The analysis of the preparation recrystallized from hot alcohol showed for N:
2.05 0/0 (0.2838 g gave 4.14 ccm n / 10 NH3 according to Iyeldahl). Theory for C- # 3 H.29 0 # -, N. S03 HCi4 H- # Oa for N: 2.19%, for S: 5.01 0%.
For the preparation of the free lobelin from your anthraquinone-p-inonosulfosariren salt suspend this in finely powdered form in water and break it down with ammonia while shaking out the base with ether. When the ether evaporates, the pure lobeline remains as a white crystalline mass which, without further purification, reacts to suitable salts, e.g. B. the chlorohydrate, can be processed in a known manner.
Example <I> 2: </I> The raw bases from Lobelia inflata are dissolved in about fifty times the amount of ether and the solution is clarified by filtration. Saturated, essential ogalic acid is then added as long as a precipitate is formed. The bases of the mixture are deposited as oxalates.
The excretion is now collected, dissolved in alcohol, and the therapeutically valuable lobeline precipitated therefrom as in Example 1 by adding an alcoholic solution of anthraquinone-β-monosulfonic acid in the form of the crystalline salt of this acid and preparing the free base from it in a known manner and their salts suitable for therapeutic use.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH102143T | 1922-11-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH102143A true CH102143A (en) | 1923-12-17 |
Family
ID=4360676
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH102143D CH102143A (en) | 1922-11-20 | 1922-11-20 | Method of rendering lobeline. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH102143A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2525785A (en) * | 1949-12-05 | 1950-10-17 | Feinstein Louis | Process for extracting alkaloidals from plants with aqueous ammoniaethylene dichloride mixture |
-
1922
- 1922-11-20 CH CH102143D patent/CH102143A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2525785A (en) * | 1949-12-05 | 1950-10-17 | Feinstein Louis | Process for extracting alkaloidals from plants with aqueous ammoniaethylene dichloride mixture |
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