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RU2002103376A - HYDROXYLATION OF COMPACTIN TO PRAVASTATIN BY MICROMONOSPORA - Google Patents

HYDROXYLATION OF COMPACTIN TO PRAVASTATIN BY MICROMONOSPORA

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Publication number
RU2002103376A
RU2002103376A RU2002103376/13A RU2002103376A RU2002103376A RU 2002103376 A RU2002103376 A RU 2002103376A RU 2002103376/13 A RU2002103376/13 A RU 2002103376/13A RU 2002103376 A RU2002103376 A RU 2002103376A RU 2002103376 A RU2002103376 A RU 2002103376A
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Russia
Prior art keywords
compound
strain
micromonospora
formula
general formula
Prior art date
Application number
RU2002103376/13A
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Russian (ru)
Other versions
RU2235780C2 (en
Inventor
Антония ЙЕККЕЛЬ
Габор АМБРУШ
Эва ИЛЬКЕИ
Ильдико ХОРВАТ
Аттила КОНЬЯ
Иштван Михай САБО
Жужанна НАДЬ
Дьюла ХОРВАТ
Юлия МОЗЕШ
Иштван Барта
Дьердь ШОМОДЬИ
Янош ШАЛАТ
Шандор Борош
Original Assignee
Дьёдьсеркутато Интезет Кфт.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Priority claimed from HU9902352A external-priority patent/HUP9902352A1/en
Application filed by Дьёдьсеркутато Интезет Кфт. filed Critical Дьёдьсеркутато Интезет Кфт.
Publication of RU2002103376A publication Critical patent/RU2002103376A/en
Application granted granted Critical
Publication of RU2235780C2 publication Critical patent/RU2235780C2/en

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Claims (7)

1. Микробный способ получения соединения формулы (I)1. Microbial method of obtaining the compounds of formula (I)
Figure 00000001
Figure 00000001
 из соединения общей формулы (II)from a compound of general formula (II)
Figure 00000002
Figure 00000002
 в которой R означает щелочной металл или ион аммония, с помощью погруженной культуры штамма Micromonospora, который способен 6β-гидроксилировать соединение формулы (II) при аэробных условиях и в результате выделения и очистки соединения формулы (I), образованного во время биоконверсии, включающей в себя стадии а) культивирования штамма Micromonospora, который способен 6β-гидроксилировать соединение формулы (II), в которой R является таким, как определено выше, при 25-32°С на питательной среде, содержащей подходящие источники углерода и азота и минеральные соли, потом b) подачи субстрата для трансформации в растущей культуре, затем c) гидроксилирования субстрата вплоть до окончания биоконверсии, затем d) выделения соединения формулы (I) из культурального бульона и, если необходимо, очистки соединения.in which R is an alkali metal or ammonium ion, using an immersed culture of a Micromonospora strain, which is capable of 6β-hydroxylating a compound of formula (II) under aerobic conditions and by isolating and purifying a compound of formula (I) formed during bioconversion, including stage a) culturing a strain of Micromonospora, which is capable of 6β-hydroxylating a compound of formula (II), in which R is as defined above, at 25-32 ° C in a nutrient medium containing suitable sources of carbon and nitrogen and mineral salts then b) feeding the substrate for transformation in a growing culture, then c) hydroxylating the substrate until the bioconversion is complete, then d) isolating the compound of formula (I) from the culture broth and, if necessary, purifying the compound. 2. Способ по п.1, в котором применяют штамм IDR-Р3 Micromonospora sp., депонированный в Национальной коллекции сельскохозяйственных и промышленных микроорганизмов, Будапешт, Венгрия, под номером NCAIM (Р) В 001268, или его мутантный штамм, который способен 6β-гидроксилировать соединение общей формулы (II).2. The method according to claim 1, which uses the strain IDR-P 3 Micromonospora sp., Deposited in the National collection of agricultural and industrial microorganisms, Budapest, Hungary, under the number NCAIM (P) B 001268, or its mutant strain, which is capable of 6β -hydroxylate a compound of general formula (II). 3. Способ по п.1, в котором применяют штамм IDR-P4 Micromonospora purpurea, депонированный в Национальной коллекции сельскохозяйственных и промышленных микроорганизмов, Будапешт, Венгрия, под номером NCAIM (P) В 001271, или его мутантный штамм, который способен 6β-гидроксилировать соединение общей формулы (II).3. The method according to claim 1, in which the strain IDR-P 4 Micromonospora purpurea, deposited in the National collection of agricultural and industrial microorganisms, Budapest, Hungary, under the number NCAIM (P) B 001271, or a mutant strain thereof which is capable of 6β-, is used. hydroxylate a compound of general formula (II). 4. Способ по п.1, в котором применяют штамм IDR-P5 Micromonospora echinispora ssp. echinospora, депонированный в Национальной коллекции сельскохозяйственных и промышленных микроорганизмов, Будапешт, Венгрия, под номером NCAIM (Р) В 001272, или его мутантный штамм, который способен 6β-гидроксилировать соединение общей формулы (II).4. The method according to claim 1, in which the strain IDR-P 5 Micromonospora echinispora ssp. echinospora deposited in the National Collection of Agricultural and Industrial Microorganisms, Budapest, Hungary, under the number NCAIM (P) B 001272, or a mutant strain thereof which is capable of 6β-hydroxylating a compound of general formula (II). 5. Способ по п.1, в котором применяют штамм IDR-P6 Micromonospora megalomicea ssp. nigra, депонированный в Национальной коллекции сельскохозяйственных и промышленных микроорганизмов, Будапешт, Венгрия, под номером NCAIM (Р) В 001273, или его мутантный штамм, который способен 6β-гидроксилировать соединение общей формулы (II).5. The method according to claim 1, in which the strain IDR-P 6 Micromonospora megalomicea ssp is used. nigra deposited in the National Collection of Agricultural and Industrial Microorganisms, Budapest, Hungary, under the number NCAIM (P) B 001273, or a mutant strain thereof which is capable of 6β-hydroxylating a compound of general formula (II). 6. Способ по п.1, в котором применяют штамм IDR-P7 Micromonospora rosaria, депонированный в Национальной коллекции сельскохозяйственных и промышленных микроорганизмов, Будапешт, Венгрия, под номером NCAIM (Р) В 001274, или его мутантный штамм, который способен 6β-гидроксилировать соединение общей формулы (II).6. The method according to claim 1, in which the strain IDR-P 7 Micromonospora rosaria is used, deposited in the National Collection of Agricultural and Industrial Microorganisms, Budapest, Hungary, under the number NCAIM (P) B 001274, or its mutant strain, which is capable of 6β- hydroxylate a compound of general formula (II). 7. Способ по любому из пп.1-6, в котором соединение формулы (I), образованное во время ферментации, выделяют из культурального бульона путем адсорции на анионообменной смоле или в результате экстракции несмешивающимся с водой органическим растворителем с последующим получением его лактонного производного или его соли вторичного амина в качестве промежуточного соединения, или в результате очистки щелочного водного экстракта, полученного из экстракта органического растворителя ферментационного бульона при хроматографии на неионной адсорбирующей смоле.7. The method according to any one of claims 1 to 6, in which the compound of formula (I) formed during fermentation is isolated from the culture broth by adsorption on an anion exchange resin or by extraction with a water-immiscible organic solvent, followed by its lactone derivative or its salts of a secondary amine as an intermediate, or as a result of purification of an alkaline aqueous extract obtained from an extract of an organic solvent of a fermentation broth by chromatography on a nonionic adsor gumming resin.
RU2002103376/13A 1999-07-12 2000-06-29 Hydroxylation of compactin to pravastatin using micromonospora RU2235780C2 (en)

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HU9902352A HUP9902352A1 (en) 1999-07-12 1999-07-12 Process for producing pravastatin by microbiological way
HUP9902352 1999-07-12

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CN114133331A (en) * 2021-12-10 2022-03-04 广东蓝宝制药有限公司 A kind of method for recovering and obtaining high-purity pravastatin ester
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