CH324078A - Process for the production of a new cardiac connection with digitalis-like effectiveness - Google Patents
Process for the production of a new cardiac connection with digitalis-like effectivenessInfo
- Publication number
- CH324078A CH324078A CH324078DA CH324078A CH 324078 A CH324078 A CH 324078A CH 324078D A CH324078D A CH 324078DA CH 324078 A CH324078 A CH 324078A
- Authority
- CH
- Switzerland
- Prior art keywords
- digitalis
- effectiveness
- production
- bovoside
- new cardiac
- Prior art date
Links
- 230000000747 cardiac effect Effects 0.000 title claims description 5
- 238000000034 method Methods 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- LXOINSCDOVUREI-GQCTYLIASA-N 3-[(e)-7-hydroperoxyperoxyhept-5-enoxy]-14-hydroxy-13-methyl-17-(6-oxopyran-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-10-carbaldehyde Chemical compound CC12CCC(C3(CCC(CC3CC3)OCCCC\C=C\COOOO)C=O)C3C1(O)CCC2C=1C=CC(=O)OC=1 LXOINSCDOVUREI-GQCTYLIASA-N 0.000 claims description 8
- 125000003172 aldehyde group Chemical group 0.000 claims description 7
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 229930182470 glycoside Natural products 0.000 claims description 4
- 150000002338 glycosides Chemical class 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000012279 sodium borohydride Substances 0.000 claims description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 2
- -1 B. methanol Chemical compound 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- OXBRMYXRHPWEIC-MXGRDHLTSA-N 5-[(3s,5r,10r,13r,14s,17r)-3-[(2r,5r)-3,5-dihydroxy-4-methoxy-6-methyloxan-2-yl]oxy-14-hydroxy-10-(hydroxymethyl)-13-methyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pyran-2-one Chemical compound OC1C(OC)[C@H](O)C(C)O[C@H]1O[C@@H]1C[C@@H](CCC2[C@]3(CC[C@@H]([C@@]3(C)CCC32)C2=COC(=O)C=C2)O)[C@]3(CO)CC1 OXBRMYXRHPWEIC-MXGRDHLTSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 241000169103 Bowiea Species 0.000 description 1
- 241000208011 Digitalis Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000006701 autoxidation reaction Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung einer neuen herzaktiven Verbindung mit digitalis-Ïhnlicher Wirksamkeit
Ans den Zwiebeln der Pflanze Bowiea solubilis Harvey ist ein herzaktives Glvkosid isoliert worden, nÏmlich das 3-¯-[1-Thevetoxy] 14¯-oxy-19-oxo-5α-bufadienolid, dem der Name Bovosid A gegeben wurde und das in 19 Stel- lung eine Aldehydgruppe aufweist (siehe A. Katz, Helv. Chim. Acta 33, 1420 [1950]).
Werden L¯sungen dieses Glvkosids, das eine digitalis-Ïhnliche Wirkung auf das Herz aus bt, an der Luft stehengelassen, so unterliegt die Aldehvdgruppe der Autoxydation. Es entsteht dabei ein Produkt, dessen Kristallisation bisher nicht gelang. Dieser Mangel an Be ständigkeit in Losungen wirkt sieh auf die Verwendung des Bovosids A für therapeu tische Zwecke sehr nachteilig aus.
Es wurde nun gefunden, dass man durch Reduktion des Bovosids A an der Aldehyd- gruppe zu einer neuen beständigen Verbin- dung gelant, die ebenfalls eine digitalis ähnliehe Wirkung auf das Herz ausübt. Die neue Verbindung, die im folgenden Bovosidol A genannt wird, besitzt eine herzaktive Wirkung.
Gegenstand der vorliegenden Erfindung ist nun ein Verfahren zur Herstellung einer neuen herzaktiven Verbindung mit digitalis- ähnlicher Wirksamkeit der Bruttoformel C31H46O9, welches dadurch kennzeichnet ist. da¯ man Bovosid A mit einem selektiv auf die Aldehydgruppe wirkenden Reduktions- mittel zur Reaktion bringt, um die Aldehyd- gruppe des Bovosids A zu einer alkoholischen Hydroxylgruppe zu reduzieren.
Das neue Glykosid Bovosidol A, das einen Smp. von 220-238¯ C und eine spezifische Drehung [a] 22/D=- 86,6¯ ¯ 2¯ (c = 1, 046 in Methanol) aufweist, ist als herzwirksames Arzneirnittel verwendbar.
Die Reduktion wird zweckmϯig in einem Losungsmittel durchgeführt. Als Lösungsmittel eignen sich beispielsweise Dioxan, Alko hole, z. B. Methanol, Wasser oder Gemische davon. Als Reduktionsmittel kann man beispielsweise Natriumborhydrid, Lithiumborhydrid, usw. verwenden. Die Temperatur, bei welcher die Reduktion durchgeführt wird, hängt weitgehend von dem im besonderen verwendeten Reduktionsmittel ab.
Beispiel
In eine Lösung von 115 mg Bovosid A in 3, 5 cm3 75%igem Dioxan wird langsam eine Lösung von 22 mg NABI4 in 2, 5 em3 75%igem Dioxan eingetropft. Die erhaltene Losung wird während 12 Stunden bei Raumtempe.. ratur stehengelassen. Die Lösung wird dann mit 2n Schwefelsäure versetzt, bis eine deutlich kongosaure Reaktion feststellbar ist, und anschliessend mit 20 em3 Wasser verdünnt.
Die erhaltene tr be Lösung wird viermal mit je 30 cm3 Chloroform ausgeschüttelt. Die Chloroformextrakte werden vereinigt, mit Wasser, 2n Sodalosung und wieder mit Was ser gewaschen, dann über wasserfreiem Na- triumsulfat getrocknet und eingedampft.
Auf diese Weise wird rohes Bovosidol A (3-fol- [@-Thevetoxy]-14¯-oxy-19-oxy-5α-bufadienolid) erhalten. Das Rohprodukt wird dureh Umkristallisierung aus einem Gemisch von Methanol und Äther gereinigt. Das umkristalli- sierte Produkt besitzt einen Smp. von 220 bis 238¯ C und eine spezifische Drehung [a] 22/D=-86,6¯ ¯ 2¯ (e = 1, 046 in Methanol). Die Ausbeute be- trägt mindestens 70 /o der theoretischen Menge.
Process for the production of a new cardiac connection with digitalis-like effectiveness
A heart-active glycoside has been isolated from the bulbs of the Bowiea solubilis Harvey plant, namely 3-¯- [1-thevetoxy] 14¯-oxy-19-oxo-5α-bufadienolide, which was given the name bovoside A and which in 19 has an aldehyde group (see A. Katz, Helv. Chim. Acta 33, 1420 [1950]).
If solutions of this glycoside, which has a digitalis-like effect on the heart, are left to stand in the air, the aldehyde group is subject to autoxidation. The result is a product that has not yet crystallized. This lack of stability in solutions has a very detrimental effect on the use of bovoside A for therapeutic purposes.
It has now been found that reducing the bovoside A on the aldehyde group leads to a new, permanent compound which also has an effect similar to digitalis on the heart. The new compound, which is called Bovosidol A in the following, has a cardiac activity.
The present invention now relates to a method for producing a new cardiac active compound with digitalis-like effectiveness of the gross formula C31H46O9, which is characterized. that bovoside A is reacted with a reducing agent that acts selectively on the aldehyde group in order to reduce the aldehyde group of bovoside A to an alcoholic hydroxyl group.
The new glycoside bovosidol A, which has a melting point of 220-238¯ C and a specific rotation [a] 22 / D = - 86.6¯ ¯ 2¯ (c = 1.046 in methanol), is a medicinal product that acts on the heart usable.
The reduction is expediently carried out in a solvent. Suitable solvents are, for example, dioxane, Alko hole, z. B. methanol, water or mixtures thereof. Sodium borohydride, lithium borohydride, etc. can be used as the reducing agent. The temperature at which the reduction is carried out depends largely on the particular reducing agent used.
example
A solution of 22 mg NABI4 in 2.5 cm3 75% dioxane is slowly added dropwise to a solution of 115 mg of bovoside A in 3.5 cm3 of 75% dioxane. The solution obtained is left to stand for 12 hours at room temperature. The solution is then admixed with 2N sulfuric acid until a clearly Congo acidic reaction can be determined, and then diluted with 20 cubic meters of water.
The cloudy solution obtained is extracted four times with 30 cm3 of chloroform each time. The chloroform extracts are combined, washed with water, 2N soda solution and again with water, then dried over anhydrous sodium sulfate and evaporated.
In this way, crude bovosidol A (3-fol- [@ -Thevetoxy] -14¯-oxy-19-oxy-5α-bufadienolide) is obtained. The crude product is purified by recrystallization from a mixture of methanol and ether. The recrystallized product has a melting point of 220 to 238¯ C and a specific rotation [a] 22 / D = -86.6¯ ¯ 2¯ (e = 1.046 in methanol). The yield is at least 70% of the theoretical amount.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH324078T | 1953-10-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH324078A true CH324078A (en) | 1957-08-31 |
Family
ID=4499391
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH324078D CH324078A (en) | 1953-10-13 | 1953-10-13 | Process for the production of a new cardiac connection with digitalis-like effectiveness |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH324078A (en) |
-
1953
- 1953-10-13 CH CH324078D patent/CH324078A/en unknown
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