NO123887B - - Google Patents
Download PDFInfo
- Publication number
- NO123887B NO123887B NO512969A NO512969A NO123887B NO 123887 B NO123887 B NO 123887B NO 512969 A NO512969 A NO 512969A NO 512969 A NO512969 A NO 512969A NO 123887 B NO123887 B NO 123887B
- Authority
- NO
- Norway
- Prior art keywords
- deserpidine
- reserpine
- nitrosation
- mixture
- production
- Prior art date
Links
- 229960001993 deserpidine Drugs 0.000 claims description 26
- CVBMAZKKCSYWQR-BPJCFPRXSA-N Deserpidine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cccc3 CVBMAZKKCSYWQR-BPJCFPRXSA-N 0.000 claims description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 claims description 13
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 claims description 11
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 claims description 11
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 claims description 11
- 229960003147 reserpine Drugs 0.000 claims description 11
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 claims description 11
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- 230000009935 nitrosation Effects 0.000 claims description 7
- 238000007034 nitrosation reaction Methods 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 241000208332 Rauvolfia Species 0.000 claims description 5
- 235000010288 sodium nitrite Nutrition 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 241000196324 Embryophyta Species 0.000 claims description 3
- 229930013930 alkaloid Natural products 0.000 claims description 3
- 150000003797 alkaloid derivatives Chemical class 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- ISMCNVNDWFIXLM-WCGOZPBSSA-N deserpidine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 ISMCNVNDWFIXLM-WCGOZPBSSA-N 0.000 claims 4
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims 2
- CVBMAZKKCSYWQR-WCGOZPBSSA-N deserpidine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=CC=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 CVBMAZKKCSYWQR-WCGOZPBSSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
Description
Framgangsmåte til framstilling av reserpinfritt deserpidin. Process for the production of reserpine-free deserpidine.
Gjenstanden for foreliggende oppfin-nelse er framstilling av reserpinfritt deserpidin fra en blanding av serserpin og deserpidin. The object of the present invention is the production of reserpine-free deserpidine from a mixture of serserpine and deserpidine.
Det er kjent at begge disse alkaloider It is known that both these alkaloids
foreligger sammen i planter av Rauwolfia-arter. Deres adskillelse var imidlertid på grunn av deres meget like fysikalske egen-skaper ytterst langvarig og vanskelig og bare mulig f.eks. ved hjelp av kromatografi eller gjentatt fraksjonert krystallisasjon. Særlig støtte framstillingen av et reserpinfritt deserpidin på vanskeligheter. present together in plants of Rauwolfia species. However, due to their very similar physical properties, their separation was extremely long and difficult and only possible e.g. by means of chromatography or repeated fractional crystallization. In particular support the production of a reserpine-free deserpidine on difficulties.
Det ble nå funnet at man kan få deserpidin reserpinfritt på enkel måte når man behandler en blanding av reserpin og deserpidin med et nitroseringsmiddel og skiller deserpidinet fra nitroseringsproduk-tene. På en overraskende måte har det nemlig vist seg at deserpidin i motsetning til reserpidin bare vanskelig angripes av disse midler. It was now found that deserpidine can be obtained reserpine-free in a simple way when you treat a mixture of reserpine and deserpidine with a nitrosating agent and separate the deserpidine from the nitrosation products. In a surprising way, it has been shown that deserpidine, in contrast to reserpidine, is only difficult to attack by these agents.
I henhold til oppfinnelsen går man According to the invention, one walks
særlig ut fra en alkaloidblanding slik som den fåes ved fremstilling av reserpin fra plantemateriale fra Rauwolfia-arter, særlig av Rauwolfia canescens, i første rekke etter en første krystallisasjon av reserpin som moderlut. Man kan også gå ut fra slike produkter som vidtgående er befridd for reserpin, henholdsvis inneholder deserpidin anriket i større mengde, f. eks. 85 deler til 15 deler reserpin, slik som de fåes ved behandling av en ekstrakt med rodanvann-stoffsyre og utskillelse av det tungtoppløse-lige reserpinsalt. in particular from an alkaloid mixture such as is obtained in the production of reserpine from plant material from Rauwolfia species, in particular Rauwolfia canescens, primarily after a first crystallization of reserpine as mother liquor. One can also assume that such products are largely free of reserpine, or contain deserpidine enriched in larger quantities, e.g. 85 parts to 15 parts reserpine, such as are obtained by treating an extract with rhododendronic acid and separating the sparingly soluble reserpine salt.
Nitroseringen utføres på i og for seg The nitrosation is carried out in and of itself
kjent måte. Den lar seg fordelaktig foreta known way. It can be advantageously carried out
med saltpetersyrling i vandig alkoholisk oppløsning. Fortrinsvis anvender man for dette natriumnitritt i eddiksur oppløsning. I første rekke arbeider man ved en temperatur på ca. 20° C, da deserpidinet delvis angripes av nitroseringsmidlet ved høyere temperaturer, slik som 50—80° C. with nitric acid in aqueous alcoholic solution. Preferably, sodium nitrite in acetic acid solution is used for this. First of all, you work at a temperature of approx. 20° C, as the deserpidine is partially attacked by the nitrosating agent at higher temperatures, such as 50-80° C.
Fra reaksjonsproduktet lar deserpidinet seg skille fra på enkel måte, f. eks. ved frafiltrering av de tungt oppløselige nitroseringsprodukter og omkrystallisasjon av deserpidinet som er lettere oppløselig i klo-roformeter. Dette lar seg rense videre på i og for seg kjent måte f. eks. ved opptak i eddiksyre, felling med ammoniakk og på-følgende omkrystallisasjon. Deserpidine can be separated from the reaction product in a simple way, e.g. by filtering off the poorly soluble nitrosation products and recrystallization of the deserpidine, which is more easily soluble in chloroform ether. This can be cleaned further in a manner known per se, e.g. by absorption in acetic acid, precipitation with ammonia and subsequent recrystallization.
Oppfinnelsen beskrives nærmere i de følgende eksempler. Temperaturene er an-gitt i Celsiusgrader. The invention is described in more detail in the following examples. The temperatures are indicated in degrees Celsius.
Eksempel 1: Example 1:
En blanding av 25 mg reserpin og 25 mg deserpidin oppløses i 2,5 cm<3> metanol og 2,5 cm<3> iseddik. Man avkjøler til 20°, tilsetter 25 cm3 0,2-n. natriumnitrit og rører mekanisk i 30 minutter. Deretter filtrerer man fra reserpinets nitroseringsprodukter og innstiller filtratet under avkjøling ved hjelp av overskudd av ammoniakkoppløs-ning alkalisk, hvorved deserpidinbasen faller ut. Det siste frafiltreres, ettervaskes i vann og tørkes ved 80°. (Utbytte 28 mg råprodukt). Rå-deserpidinet oppløses i 0,5 cm<3> kloroform og tilsettes 10 cm<3> eter og 5 cm3 petroleter. De utskilte brune fnokker filtreres fra, og resten ettervaskes med en eter-petroleter-blanding (2:1). Man ryster filtratet 7 ganger med hver gang 25 cm<3>A mixture of 25 mg of reserpine and 25 mg of deserpidine is dissolved in 2.5 cm<3> of methanol and 2.5 cm<3> of glacial acetic acid. Cool to 20°, add 25 cm3 0.2-n. sodium nitrite and stir mechanically for 30 minutes. The nitrosation products of the reserpine are then filtered and the filtrate is made alkaline while cooling with the help of an excess of ammonia solution, whereby the deserpidine base precipitates out. The latter is filtered off, washed in water and dried at 80°. (Yield 28 mg crude product). The crude deserpidine is dissolved in 0.5 cm<3> of chloroform and 10 cm<3> of ether and 5 cm3 of petroleum ether are added. The separated brown flakes are filtered off, and the residue is washed with an ether-petroleum ether mixture (2:1). The filtrate is shaken 7 times, each time 25 cm<3>
2-n. eddiksyre, tilsetter de sammenslåtte og filtrerte uttrekk under avkjøling overskudd av ammoniakk og skiller fra den utfelte deserpidinbase ved filtrering. Etter tørking får man 21 mg deserpidin med sm.p. 225— 230°. 2-n. acetic acid, add to the combined and filtered extracts during cooling an excess of ammonia and separate from the precipitated deserpidine base by filtration. After drying, 21 mg of deserpidine with m.p. 225-230°.
Eksempel 2: En blanding av 75 mg deserpidin og 25 mg reserpin oppløses i 2,5 cm:! metanol og 2,5 cm:! iseddik og tilsettes 30 cm3 0,2-n. natriumnitrit ved 20° C. Etter god omrøring i 30 minutter ved denne temperatur frafiltreres og ettervaskes med vann. Resten oppløser man i 2,5 cm3 metanol og 5 cm3 is-edikk, tilsetter 25 cm3 0,2-n. natriumnitrit ved 20° C, rører kraftig i 30 minutter ved denne temperatur og filtrerer fra uoppløse-lige deler. De således erholdte filtrater slås sammen, tilsettes 25 cm<3> konsentrert am-moniakkoppløsning (ca. 30 %'s) og den utfelte deserpidinbase skilles fra. Tørket ved 80° C fåes 64 mg råprodukt. Dette opptas i 0,5 cm3 kloroform, oppløsningen tilsettes 10 cm<:i> eter og 5 cm<3> petroleter, de utskilte brune fnokker avfiltreres, og resten utvas-kes med en eter-petroleter-blanding 2:1. Example 2: A mixture of 75 mg deserpidine and 25 mg reserpine is dissolved in 2.5 cm:! methanol and 2.5 cm:! glacial acetic acid and add 30 cm3 0.2-n. sodium nitrite at 20° C. After stirring well for 30 minutes at this temperature, filter off and wash with water. The residue is dissolved in 2.5 cm3 of methanol and 5 cm3 of glacial acetic acid, and 25 cm3 of 0.2-n is added. sodium nitrite at 20° C., stir vigorously for 30 minutes at this temperature and filter from insoluble parts. The filtrates thus obtained are combined, 25 cm<3> of concentrated ammonia solution (approx. 30%) are added and the precipitated deserpidine base is separated. Dried at 80° C, 64 mg of crude product is obtained. This is taken up in 0.5 cm3 of chloroform, 10 cm<:i> of ether and 5 cm<3> of petroleum ether are added to the solution, the separated brown flakes are filtered off, and the residue is washed out with an ether-petroleum ether mixture 2:1.
Filtratet ryster man 7 ganger med hver gang 25 cm<3> 2-n. eddiksyre, tilsetter de sammenslåtte og filtrerte uttrekk under avkjøling overskudd av ammoniakk og skiller fra den utfelte deserpidinbase ved filtrering. Etter tørking får man 50 mg deserpidin med smeltepunkt 225—230° C. The filtrate is shaken 7 times, each time 25 cm<3> 2-n. acetic acid, add to the combined and filtered extracts during cooling an excess of ammonia and separate from the precipitated deserpidine base by filtration. After drying, 50 mg of deserpidine with a melting point of 225-230° C is obtained.
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO512969A NO123887B (en) | 1969-12-24 | 1969-12-24 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO512969A NO123887B (en) | 1969-12-24 | 1969-12-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO123887B true NO123887B (en) | 1972-01-31 |
Family
ID=19880806
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO512969A NO123887B (en) | 1969-12-24 | 1969-12-24 |
Country Status (1)
| Country | Link |
|---|---|
| NO (1) | NO123887B (en) |
-
1969
- 1969-12-24 NO NO512969A patent/NO123887B/no unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3846490A (en) | Method of producing zeta-aminolevulinic acid hydrochloride | |
| NO123887B (en) | ||
| Fuson et al. | The haloform reaction. XIV. an improved iodoform test | |
| DE1021831B (en) | Process for the production of pure crystallized ammonium bifluoride from fluosilicic acid and ammonia | |
| US2841587A (en) | Separation of mixtures of deserpidine | |
| AT204706B (en) | Process for obtaining reserpine-free deserpidine | |
| KITAGAWA et al. | STUDIES ON A DIAMINO ACID, CANAVANIN VI. The formation of desamino canavanin from canavanin | |
| US1947717A (en) | Cocoa product and process of making same | |
| US3244696A (en) | Extraction of alkaloids from plants of genus holarrhena | |
| Manske | The Alkaloids of Fumaraceous Plants: IV. Adlumia fungosa, Greene | |
| US4162255A (en) | Process for extracting aristolochic acids | |
| US2421118A (en) | Plant extracts and method of producing same | |
| SU38235A1 (en) | The method of obtaining dehydrodiotoluenhdig | |
| Thompson et al. | Preparation of Crystalline Anhydrous β-Gentiobiose | |
| CH341504A (en) | Process for obtaining a pure alkaloid | |
| NO123928B (en) | ||
| US2333050A (en) | Separating hematoxylin from logwood extract | |
| DE643699C (en) | Process for the preparation of azo compounds of the quinoline series | |
| AT215419B (en) | Process for the preparation of (5-nitrofuryl) methyl ketone | |
| US2887489A (en) | Process and intermediate for | |
| DE1058520B (en) | Process for obtaining reserpine-free deserpidine | |
| Brady et al. | LXI.—The dinitrotoluidines | |
| SU123961A1 (en) | The method of selection of glucoalkaloids avian nightshade | |
| SU148046A1 (en) | Method for producing cortisone acetate | |
| SU485976A1 (en) | The method of obtaining octammine-m-amino-ol-dicobaltihloride |