AT274248B - Process for the preparation of new derivatives of bufadienolide glycosides - Google Patents
Process for the preparation of new derivatives of bufadienolide glycosidesInfo
- Publication number
- AT274248B AT274248B AT1181367A AT1181367A AT274248B AT 274248 B AT274248 B AT 274248B AT 1181367 A AT1181367 A AT 1181367A AT 1181367 A AT1181367 A AT 1181367A AT 274248 B AT274248 B AT 274248B
- Authority
- AT
- Austria
- Prior art keywords
- bufadienolide
- glycosides
- preparation
- new derivatives
- general formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 6
- -1 derivatives of bufadienolide glycosides Chemical class 0.000 title claims description 4
- 229930182470 glycoside Natural products 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 8
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 claims description 2
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 2
- 239000012024 dehydrating agents Substances 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- MYEJFUXQJGHEQK-ALRJYLEOSA-N Proscillaridin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C=C2CC[C@H]3[C@@]4(O)CC[C@H](C5=COC(=O)C=C5)[C@@]4(C)CC[C@@H]3[C@@]2(C)CC1 MYEJFUXQJGHEQK-ALRJYLEOSA-N 0.000 description 3
- 229960003584 proscillaridin Drugs 0.000 description 3
- MYEJFUXQJGHEQK-UHFFFAOYSA-N proscillaridin A Natural products OC1C(O)C(O)C(C)OC1OC1C=C2CCC3C4(O)CCC(C5=COC(=O)C=C5)C4(C)CCC3C2(C)CC1 MYEJFUXQJGHEQK-UHFFFAOYSA-N 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- DKVBOUDTNWVDEP-NJCHZNEYSA-N teicoplanin aglycone Chemical compound N([C@H](C(N[C@@H](C1=CC(O)=CC(O)=C1C=1C(O)=CC=C2C=1)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)OC=1C=C3C=C(C=1O)OC1=CC=C(C=C1Cl)C[C@H](C(=O)N1)NC([C@H](N)C=4C=C(O5)C(O)=CC=4)=O)C(=O)[C@@H]2NC(=O)[C@@H]3NC(=O)[C@@H]1C1=CC5=CC(O)=C1 DKVBOUDTNWVDEP-NJCHZNEYSA-N 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
<Desc/Clms Page number 1>
Verfahren zur Herstellung neuer Derivate von Bufadienolidglykosiden
Die Erfindung betrifft ein Verfahren zur Herstellung neuer Derivate von Bufadienolidglykosiden der allgemeinen Formel
EMI1.1
In dieser Formel bedeuten R, ein Wasserstoffatom oder den Acetylrest, Rz und Rs, die gleich oder verschieden sein können, Wasserstoffatome, gegebenenfalls halogensubstituierte Alkylreste oder zusamsen, mit dem benachbarten Kohlenstoffatom einen alicyclischen Ring mit 5 bis 7 Kohlenstoffatomen.
Die neuen Verbindungen sind also Derivate des Scilliglaucosidin-a-L-rhamnosids. Das Scilliglau- cosidin-a-L-rhamnosid selbst ist eine neue Verbindung, die aus den bei der Gewinnung des Proscillaridin A anfallenden Mutterlaugen isoliert werden kann. Diese Mutterlaugen werden zunächst 45 min mit piger Schwefelsäure in 50%igem Methanol unter Rückfluss gekocht, wobei das Proscillaridin A gespalten wird, nicht jedoch das Scilliglaucosidin-a-L-rhamnosid. Letzteres wird von dem Aglykon des Proscillaridin A durch Säulenchromatographie an wasserhaltigem Kieselgel mittels eines Gemisches von Methylenchlorid und Methanol im Verhältnis 100 : 5 getrennt.
Der Schmelzpunkt der reinen Verbin-
EMI1.2
<Desc/Clms Page number 2>
beträgt-470 20 (c = 1, Me-Erfindungsgemäss werden die neuen Verbindungen durch Umsetzung einer Verbindung der allgemeinen Formel
EMI2.1
mit einer Verbindung der allgemeinen Formel
EMI2.2
EMI2.3
<Desc/Clms Page number 3>
Die Umsetzung wird dünnschichtchromatographisch verfolgt. Nach beendeter Reaktion wird das Kupfersulfat über einen Filter, abgedichtet mit Aluminiumoxyd (AO nach Woelm Aktiv. Stufe I), abgesaugt. Das klare Filtratwird zur Trockene eingeengt und aus 60 ml Methanol umkristallisiert. Die Substanz kristallisiert in farblosen Stäbchen.
Ausbeute : 1, 4 g (87, 00/0 der Theorie)
F. : 164 bis 1670 C (Zers.).
B eis pi el 2 : 3B- (2I, 31-0-Isopropyliden-41-acetyl) -a-L-rhamnosido-14B-hydroxy-19-oxo-bufa- - 4, 20,22-trienolid.
1, 6 g 3ss- (2t, 31-0-Isopropyliden)-a-L-rhamnosido-14ss-hydroxy-19-oxo-bufa-4, 20,22-trienolid, gelöst in 12,0 ml Pyridin und 8,0 ml Acetanhydrid, werden 24 h bei 200 C stehengelassen. Das Ende der Reaktion wird dünnschichtchromatographisch festgestellt. Nach beendeter Reaktion wird imVakuum bei 500 C zur Trockene eingeengt. Der sirupartige Rückstand wird in 50 ml Chloroform gelöst und mit Wasser 2n HCl, Wasser, 2n Sodalösung und Wasser gewaschen. Nach Trocknen über Natriumsulfat wird erneut im Vakuum zur Trockene eingeengt. Der farblose, amorphe Rückstand wird aus 40 ml warmem Methanol umkristallisiert. Die Substanz kristallisiert in farblosen Nadeln.
Ausbeute : 1, 3 g (76, oxo der Theorie)
F. : 228 bis 2310 C (Zers.).
B e i s p i e l 3: 3ss-(2',3'-O-Methyl-propyliden)-α-L-rhamnosido-14ss-hydroxy-19-oxo-bufa-4,20, 22-trienolid
200 mg 3ss-ct-L-Rhamnosido-14ss-hydroxy-19-oxo-bufa-4, 20,22-trienolid, 1, 5 g Kupfersulfat und 80 ml Methyläthylketon werden analog Beispiel 1 umgesetzt und aufgearbeitet. Umkristallisation aus Äther : n-Hexan = 6 : 1 ergeben 130 mg weisse Kristalle (59% der Theorie) vom
Fp. : 143 bis 1460 C.
B e i s p i e l 4: 3ss-(2',3'-O-Trichloräthyliden)-α-L-rahmnosido-14ss-hydroxy-19-oxo-bufa-4, 20, 22-trienolid
EMI3.1
abdestilliert, der Rückstand in Chloroform gelöst und gewaschen und zur Trockene eingeengt. Umkristallisation aus Äther : n-Hexan = 5 : 1 ergeben 53 mg gelbliche Kristalle in Blättchenform (43% der Theorie) vom
Fp. : 80 bis 860 C.
**WARNUNG** Ende DESC Feld kannt Anfang CLMS uberlappen**.
<Desc / Clms Page number 1>
Process for the preparation of new derivatives of bufadienolide glycosides
The invention relates to a process for the preparation of new derivatives of bufadienolide glycosides of the general formula
EMI1.1
In this formula, R, a hydrogen atom or the acetyl radical, Rz and Rs, which can be identical or different, denote hydrogen atoms, optionally halogen-substituted alkyl radicals or together with the adjacent carbon atom, an alicyclic ring having 5 to 7 carbon atoms.
The new compounds are therefore derivatives of scilliglaucosidine-a-L-rhamnoside. The scilliglaucosidin-a-L-rhamnoside itself is a new compound that can be isolated from the mother liquors obtained during the production of proscillaridin A. These mother liquors are first refluxed for 45 minutes with pigerous sulfuric acid in 50% methanol, the proscillaridin A being cleaved, but not the scilliglaucosidin-a-L-rhamnoside. The latter is separated from the aglycon of proscillaridin A by column chromatography on water-containing silica gel using a mixture of methylene chloride and methanol in a ratio of 100: 5.
The melting point of the pure compound
EMI1.2
<Desc / Clms Page number 2>
is -470 20 (c = 1, Me-According to the invention, the new compounds are obtained by reacting a compound of the general formula
EMI2.1
with a compound of the general formula
EMI2.2
EMI2.3
<Desc / Clms Page number 3>
The reaction is followed by thin layer chromatography. After the reaction has ended, the copper sulphate is suctioned off through a filter sealed with aluminum oxide (AO according to Woelm Aktiv. Level I). The clear filtrate is concentrated to dryness and recrystallized from 60 ml of methanol. The substance crystallizes in colorless rods.
Yield: 1.4 g (87.00/0 of theory)
F.: 164 to 1670 C (dec.).
Example 2: 3B- (2I, 31-0-isopropylidene-41-acetyl) -a-L-rhamnosido-14B-hydroxy-19-oxo-bufa- -4, 20,22-trienolide.
1.6 g of 3ss- (2t, 31-0-isopropylidene) -aL-rhamnosido-14ss-hydroxy-19-oxo-bufa-4, 20,22-trienolide, dissolved in 12.0 ml of pyridine and 8.0 ml Acetic anhydride, are left to stand at 200 ° C. for 24 hours. The end of the reaction is determined by thin layer chromatography. When the reaction has ended, the mixture is concentrated to dryness in vacuo at 500 ° C. The syrupy residue is dissolved in 50 ml of chloroform and washed with water, 2N HCl, water, 2N soda solution and water. After drying over sodium sulfate, it is again concentrated to dryness in vacuo. The colorless, amorphous residue is recrystallized from 40 ml of warm methanol. The substance crystallizes in colorless needles.
Yield: 1.3 g (76, oxo of theory)
F.: 228 to 2310 C (dec.).
Example 3: 3ss- (2 ', 3'-O-methyl-propylidene) -α-L-rhamnosido-14ss-hydroxy-19-oxo-bufa-4,20,22-trienolide
200 mg of 3ss-ct-L-rhamnosido-14ss-hydroxy-19-oxo-bufa-4, 20,22-trienolide, 1.5 g of copper sulfate and 80 ml of methyl ethyl ketone are reacted and worked up analogously to Example 1. Recrystallization from ether: n-hexane = 6: 1 gives 130 mg of white crystals (59% of theory) from
M.p .: 143 to 1460 C.
Example 4: 3ss- (2 ', 3'-O-trichloroethylidene) -α-L-rahmnosido-14ss-hydroxy-19-oxo-bufa-4, 20, 22-trienolide
EMI3.1
distilled off, the residue dissolved in chloroform and washed and concentrated to dryness. Recrystallization from ether: n-hexane = 5: 1 gives 53 mg of yellowish crystals in flake form (43% of theory) from
M.p .: 80 to 860 C.
** WARNING ** End of DESC field may overlap beginning of CLMS **.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE274248X | 1966-12-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AT274248B true AT274248B (en) | 1969-09-10 |
Family
ID=6019525
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT1181367A AT274248B (en) | 1966-12-30 | 1967-12-29 | Process for the preparation of new derivatives of bufadienolide glycosides |
Country Status (1)
| Country | Link |
|---|---|
| AT (1) | AT274248B (en) |
-
1967
- 1967-12-29 AT AT1181367A patent/AT274248B/en active
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