NO146078B - DEVICE OR BRAND STAKE - Google Patents
DEVICE OR BRAND STAKE Download PDFInfo
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- NO146078B NO146078B NO793555A NO793555A NO146078B NO 146078 B NO146078 B NO 146078B NO 793555 A NO793555 A NO 793555A NO 793555 A NO793555 A NO 793555A NO 146078 B NO146078 B NO 146078B
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- Prior art keywords
- rifamycin
- stake
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- methanol
- water
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- RAFHKEAPVIWLJC-OQQFTUDCSA-N Rifamycin O Natural products COC1C=COC2(C)Oc3c(C)c(O)c4C(=O)C(=CC5(OCC(=O)O5)c4c3C2=O)NC(=O)C(=C/C=C/C(C)C(O)C(C)C(O)C(C)C(OC(=O)C)C1C)C RAFHKEAPVIWLJC-OQQFTUDCSA-N 0.000 claims description 15
- RAFHKEAPVIWLJC-TWYIRNIGSA-N z67lem9p1w Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)N2)C)OC)C(C(=C3O)C)=C1C1=C3C(=O)C2=C[C@]11OCC(=O)O1 RAFHKEAPVIWLJC-TWYIRNIGSA-N 0.000 claims description 15
- SQTCRTQCPJICLD-KTQDUKAHSA-N rifamycin B Chemical compound OC1=C(C(O)=C2C)C3=C(OCC(O)=O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O SQTCRTQCPJICLD-KTQDUKAHSA-N 0.000 claims description 8
- SQTCRTQCPJICLD-OQQFTUDCSA-N rifomycin-B Natural products COC1C=COC2(C)Oc3c(C)c(O)c4c(O)c(NC(=O)C(=C/C=C/C(C)C(O)C(C)C(O)C(C)C(OC(=O)C)C1C)C)cc(OCC(=O)O)c4c3C2=O SQTCRTQCPJICLD-OQQFTUDCSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 4
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 229930189077 Rifamycin Natural products 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229960003292 rifamycin Drugs 0.000 description 5
- HJYYPODYNSCCOU-ODRIEIDWSA-N rifamycin SV Chemical compound OC1=C(C(O)=C2C)C3=C(O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O HJYYPODYNSCCOU-ODRIEIDWSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- BTVYFIMKUHNOBZ-ZDHWWVNNSA-N Rifamycin S Natural products COC1C=COC2(C)Oc3c(C)c(O)c4C(=O)C(=CC(=O)c4c3C2=O)NC(=O)C(=C/C=C/C(C)C(O)C(C)C(O)C(C)C(OC(=O)C)C1C)C BTVYFIMKUHNOBZ-ZDHWWVNNSA-N 0.000 description 2
- BTVYFIMKUHNOBZ-ODRIEIDWSA-N Rifamycin S Chemical compound O=C1C(C(O)=C2C)=C3C(=O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O BTVYFIMKUHNOBZ-ODRIEIDWSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- ZYECOAILUNWEAL-NUDFZHEQSA-N (4z)-4-[[2-methoxy-5-(phenylcarbamoyl)phenyl]hydrazinylidene]-n-(3-nitrophenyl)-3-oxonaphthalene-2-carboxamide Chemical compound COC1=CC=C(C(=O)NC=2C=CC=CC=2)C=C1N\N=C(C1=CC=CC=C1C=1)/C(=O)C=1C(=O)NC1=CC=CC([N+]([O-])=O)=C1 ZYECOAILUNWEAL-NUDFZHEQSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
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- Special Spraying Apparatus (AREA)
Description
Fremgangsmåte til fremstilling av rifamycin O. Process for the production of rifamycin O.
Foreliggende oppfinnelse angår en fremgangsmåte til fremstilling av rifamycin O. The present invention relates to a method for the production of rifamycin O.
I patentene nr. 103 127 og 103 128 er det beskrevet fremstilling av antibiotikum rifamycin ved dyrkning av en stamme av Str. mediterranei. Rifamycin består av flere komponenter med høy antibiotisk virkning. En av disse komponenter, rifamycin B, utgjør utgangsforbindelsen for fremstilling av antibiotikum ifølge foreliggende oppfinnelse. Patents no. 103 127 and 103 128 describe the production of the antibiotic rifamycin by cultivating a strain of Str. mediterranei. Rifamycin consists of several components with a high antibiotic effect. One of these components, rifamycin B, constitutes the starting compound for the production of the antibiotic according to the present invention.
Rifamycin B er bestandig i lengere Rifamycin B is persistent for longer
tid i krystallinsk form, men omleirer seg når det oppbevares som sådant, eller i form av et salt oppløst i vann eller i luf-ten. Det er kjent at mange antibiotika, når de er oppløst eller suspendert i vann, raskt spaltes under dannelse av stoffer som ikke har noen praktisk interesse. Det-te gjelder imidlertid ikke for rifamycin B, som omdanner seg til videre antibiotiske stoffer med høyere virkning enn rifamycin B. Skjønt reaksjonsmekanismen for denne omdannelse ikke er fullstendig time in crystalline form, but redeposits when stored as such, or in the form of a salt dissolved in water or in the air. It is known that many antibiotics, when dissolved or suspended in water, rapidly decompose to form substances of no practical interest. However, this does not apply to rifamycin B, which is converted into further antibiotic substances with a higher effect than rifamycin B. Although the reaction mechanism for this conversion is not complete
klarlagt, antar man at den består i en ok-sydasjon som er forårsaket av den atmos-færiske luft. Utfører man oksydasjonen under kontrollerte betingelser, dvs. ved omtrent nøytral pH-verdi i et oppløs-ningsmiddel, slik som en vandig lavere alifatisk alkohol med f. eks. hydrogenperoksyd eller salpetersyrling, oppstår rifamycin O, som etter tilsetning av sterke syrer gradvis går over i rifamycin S. clarified, it is assumed that it consists of an ok-sydation which is caused by the atmospheric air. The oxidation is carried out under controlled conditions, i.e. at an approximately neutral pH value in a solvent, such as an aqueous lower aliphatic alcohol with e.g. hydrogen peroxide or nitric acid, rifamycin O is formed, which after the addition of strong acids gradually turns into rifamycin S.
Isoleringen av rifamycin O lettes når The isolation of rifamycin O is facilitated when
man utfører oksydasjonen i fravær av rifamycin O-oppløsende oppløsningsmldler, slik som aceton. Rifamycin O faller da ut så snart det tilsettes vandig mineral-syreoppløsning. De utfelte krystaller oppsamles og tørkes. the oxidation is carried out in the absence of rifamycin O-dissolving solvents, such as acetone. Rifamycin O then precipitates as soon as an aqueous mineral-acid solution is added. The precipitated crystals are collected and dried.
Rifamycin O er et lysegult krystallinsk stoff som spaltes ved 160° C og ikke smel-ter under 300° C. [a] 2° = 71,5° (c = 1 i dioksan). Det er uoppløselig i vann og fortynnete mineralsyrer. I alkalihydrok-syder oppløses det gradvis med sterk rød-fiolett farve. I metanol, etanol og etyl-acetat er det bare litt oppløselig, men derimot temmelig godt oppløselig i aceton. Rifamycin O gir positiv ferriklorid-, Feh-ling- og Tollens-reaksjoner. Det reagerer svakt surt. Den potentiometriske bestem-melse i vandig metanol ga to svakt sure grupper (pK, 1/2, 7,7, pK2 1/2, 10,75). Rifamycin O is a pale yellow crystalline substance which decomposes at 160° C and does not melt below 300° C. [a] 2° = 71.5° (c = 1 in dioxane). It is insoluble in water and dilute mineral acids. In alkali hydroxides it gradually dissolves with a strong red-violet colour. In methanol, ethanol and ethyl acetate it is only slightly soluble, but on the other hand fairly well soluble in acetone. Rifamycin O gives positive ferric chloride, Fehling and Tollens reactions. It reacts slightly sour. The potentiometric determination in aqueous methanol gave two weakly acidic groups (pK, 1/2, 7.7, pK2 1/2, 10.75).
Det ultrafiolette absorpsjonsspektrum av rifamycin O i metanol viser maksima ved 226 imi (E \ fm= 365). 273 m|.i The ultraviolet absorption spectrum of rifamycin O in methanol shows maxima at 226 nm (E \ fm = 365). 273 m|.i
(<E>lcm = 440> og 370 m^ (<E>l<c>m = 60)>(<E>lcm = 440> and 370 m^ (<E>l<c>m = 60)>
sammenlign fig. 1. compare fig. 1.
Det infrarøde absorpsjonsspektrum viser følgende maksima: 3380, 3100, 2925 (mineralolje), 2850 (mineralolje), 1822, 1728, 1682, 1660, 1635, 1605, 1513, 1465 (mineralolje), 1418, 1382 (mineralolje), 1347, 1310, 1257, 1212, 1187, 1174, 1137, 1120, 1100, 1084, 1072, 1025, 980, 952, 925, 910, 896, 846, 820, 793, 783, 757, 725, 680 cm-<1>, sammenlign fig. 2. The infrared absorption spectrum shows the following maxima: 3380, 3100, 2925 (mineral oil), 2850 (mineral oil), 1822, 1728, 1682, 1660, 1635, 1605, 1513, 1465 (mineral oil), 1418, 1382 (mineral oil), 1347, 1310 , 1257, 1212, 1187, 1174, 1137, 1120, 1100, 1084, 1072, 1025, 980, 952, 925, 910, 896, 846, 820, 793, 783. compare fig. 2.
Maksimum ved 1822 cm-<1> er karakte-ristisk og dets gradvise forsvinning kan betraktes som grad for omdannelse av rifamycin O til rifamycin S. The maximum at 1822 cm-<1> is characteristic and its gradual disappearance can be regarded as the degree of conversion of rifamycin O to rifamycin S.
Elementæranalysen ga følgende ver-dier: C pst. 62,53, H pst.: 6,64, N pst. 1,74, O pst. 29,37, OCH3 pst. 4,23, COCH;1 pst. 5,59. Derav kunne følgende bruttoformiel utledes: The elemental analysis gave the following values: C % 62.53, H %: 6.64, N % 1.74, O % 29.37, OCH3 % 4.23, COCH;1 % 5, 59. The following gross formula could be derived from this:
Ved behandling med eddiksyreanhydrid i pyridin, gir rifamycin © et monoacetyl-derivat med smeltepunkt ,203—205° C. Ved behandling med ascorfoinsyre går rifamycin O i godt utbytte igjen over i rifamycin B. When treated with acetic anhydride in pyridine, rifamycin © gives a monoacetyl derivative with a melting point of 203-205° C. When treated with ascorfoic acid, rifamycin O converts again to rifamycin B in good yield.
Rifamycin Cs høye antibakterielle virkning fremgår av følgende tabell. Tal-lene angir den minste hemmende kon-sentrasjon i y/cm<3> like overfor en rekke patogene organismer. Rifamycin C's high antibacterial effect is shown in the following table. The numbers indicate the minimum inhibitory concentration in y/cm<3> against a number of pathogenic organisms.
Følgende eksempler forklarer frem-gangsmåten ifølge oppfinnelsen. The following examples explain the method according to the invention.
Eksempel 1. Example 1.
En oppløsning av 10 g rifamycin B i 2000 cm3 metanol tilsettes 3000 cm3 vann og 100 cm' av en 40 pst.'ig hydrogenper-oksydoppløsning. Etter 30 min. oppvarm-ning til 45—50° C avkjøles blandingen til 0° C. De utskilte krystaller oppsamles og tørkes i vakuum ved 40° C. Utbytte 6,5 g rifamycin O. A solution of 10 g of rifamycin B in 2000 cm3 of methanol is added to 3000 cm3 of water and 100 cm3 of a 40% hydrogen peroxide solution. After 30 min. heating to 45-50° C, the mixture is cooled to 0° C. The separated crystals are collected and dried in vacuum at 40° C. Yield 6.5 g of rifamycin O.
Eksempel 2. Example 2.
En oppløsning av 10 g rifamycin B i 2000 cm<3> metanol tilsettes først en opp-løsning av 50 g natriuminitrit i 250 cm3' vann og deretter den støkiometriske meng-de 10 pst.ig saltsyre inntil reaksjonen er svakt sur. (pH-verdi ca. 4,0). Under syre-tilsetningen faller rifamycin O ut. Etter avkjøling til 0° C oppsamles bunnfallet og tørkes. Utbytte 9 g rifamycin O. Ved om-krystallisasjon fra metanol fås 8,5 g rent rifamycin O. A solution of 10 g of rifamycin B in 2000 cm3 of methanol is first added to a solution of 50 g of sodium nitrite in 250 cm3 of water and then the stoichiometric amount of 10% hydrochloric acid until the reaction is slightly acidic. (pH value approx. 4.0). During the acid addition, rifamycin O precipitates out. After cooling to 0° C, the precipitate is collected and dried. Yield 9 g of rifamycin O. Recrystallization from methanol yields 8.5 g of pure rifamycin O.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO793555A NO146078C (en) | 1979-11-05 | 1979-11-05 | DEVICE OR BRAND STAKE |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO793555A NO146078C (en) | 1979-11-05 | 1979-11-05 | DEVICE OR BRAND STAKE |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO793555L NO793555L (en) | 1981-05-06 |
| NO146078B true NO146078B (en) | 1982-04-19 |
| NO146078C NO146078C (en) | 1982-07-28 |
Family
ID=19885135
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO793555A NO146078C (en) | 1979-11-05 | 1979-11-05 | DEVICE OR BRAND STAKE |
Country Status (1)
| Country | Link |
|---|---|
| NO (1) | NO146078C (en) |
-
1979
- 1979-11-05 NO NO793555A patent/NO146078C/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO793555L (en) | 1981-05-06 |
| NO146078C (en) | 1982-07-28 |
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