UA73493C2 - A microbiological process for the preparation of pravastatin and biologically pure culture mortierella maculata, being used in this process - Google Patents

A microbiological process for the preparation of pravastatin and biologically pure culture mortierella maculata, being used in this process Download PDF

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Publication number: UA73493C2
Authority: UA; Ukraine
Prior art keywords: formula; compound; pravastatin; strain; broth
Prior art date: 1999-02-03

Application number

UA2001086010A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Inst Drugs Res Ltd

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.)

1999-02-03

Filing date

2000-03-02

Publication date

2005-08-15

2000-02-03 Priority claimed from PCT/US2000/002993 external-priority patent/WO2000046175A1/en

2000-03-02 Application filed by Inst Drugs Res Ltd filed Critical Inst Drugs Res Ltd

2005-08-15 Publication of UA73493C2 publication Critical patent/UA73493C2/uk

Links

TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 title claims abstract description 128
229960002965 pravastatin Drugs 0.000 title claims abstract description 128
TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 title claims abstract description 124
238000000034 method Methods 0.000 title claims abstract description 57
230000008569 process Effects 0.000 title abstract description 5
241000235575 Mortierella Species 0.000 title abstract 2
238000002360 preparation method Methods 0.000 title abstract 2
230000002906 microbiologic effect Effects 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 40
238000000855 fermentation Methods 0.000 claims abstract description 32
230000004151 fermentation Effects 0.000 claims abstract description 32
150000003839 salts Chemical class 0.000 claims abstract description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 11
229910052799 carbon Inorganic materials 0.000 claims abstract description 8
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 5
239000011707 mineral Substances 0.000 claims abstract description 5
235000015097 nutrients Nutrition 0.000 claims abstract description 4
238000000926 separation method Methods 0.000 claims abstract description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 111
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 93
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 60
239000000758 substrate Substances 0.000 claims description 49
239000000203 mixture Substances 0.000 claims description 44
VGMFHMLQOYWYHN-UHFFFAOYSA-N Compactin Natural products OCC1OC(OC2C(O)C(O)C(CO)OC2Oc3cc(O)c4C(=O)C(=COc4c3)c5ccc(O)c(O)c5)C(O)C(O)C1O VGMFHMLQOYWYHN-UHFFFAOYSA-N 0.000 claims description 43
AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 claims description 43
AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 claims description 43
BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 claims description 43
239000000243 solution Substances 0.000 claims description 43
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 23
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BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical class C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 claims description 22
239000000725 suspension Substances 0.000 claims description 20
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-1 2-methylbutyryl Chemical group 0.000 claims description 12
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XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims description 5
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RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 4
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WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 4
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239000005018 casein Substances 0.000 claims description 3
BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 claims description 3
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235000013372 meat Nutrition 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 2
125000003710 aryl alkyl group Chemical group 0.000 claims description 2
125000003118 aryl group Chemical group 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
229920003053 polystyrene-divinylbenzene Polymers 0.000 claims description 2
125000001453 quaternary ammonium group Chemical group 0.000 claims description 2
238000005406 washing Methods 0.000 claims description 2
150000005215 alkyl ethers Chemical class 0.000 claims 3
SZNYYWIUQFZLLT-UHFFFAOYSA-N 2-methyl-1-(2-methylpropoxy)propane Chemical group CC(C)COCC(C)C SZNYYWIUQFZLLT-UHFFFAOYSA-N 0.000 claims 2
238000011033 desalting Methods 0.000 claims 1
238000005227 gel permeation chromatography Methods 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
241000894007 species Species 0.000 abstract description 12
238000000746 purification Methods 0.000 abstract description 5
238000010564 aerobic fermentation Methods 0.000 abstract 1
230000007483 microbial process Effects 0.000 abstract 1
235000010633 broth Nutrition 0.000 description 40
239000002609 medium Substances 0.000 description 40
229920001817 Agar Polymers 0.000 description 21
239000008272 agar Substances 0.000 description 20
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 19
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
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OQARDMYXSOFTLN-PZAWKZKUSA-N pravastatin lactone Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 OQARDMYXSOFTLN-PZAWKZKUSA-N 0.000 description 13
230000001954 sterilising effect Effects 0.000 description 13
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BOZILQFLQYBIIY-INTXDZFKSA-N mevinic acid Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)CCC=C21 BOZILQFLQYBIIY-INTXDZFKSA-N 0.000 description 11
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Preparation Of Compounds By Using Micro-Organisms (AREA)

UA2001086010A 1999-02-03 2000-03-02 A microbiological process for the preparation of pravastatin and biologically pure culture mortierella maculata, being used in this process UA73493C2 (en)

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- 2000-02-03 RU RU2001121943/13A patent/RU2252258C2/ru not_active IP Right Cessation
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Also Published As

Publication number	Publication date
CN1328369C (zh)	2007-07-25
CN1814766A (zh)	2006-08-09
ZA200106359B (en)	2002-08-02
RU2252258C2 (ru)	2005-05-20

Publication	Publication Date	Title
CA2361701C (en)	2007-04-10	Microbial process for preparing pravastatin
US6682913B1 (en)	2004-01-27	Microbial process for preparing pravastatin
KR100479837B1 (ko)	2005-03-31	마이크로모노스포라 균주를 이용한 프라바스타틴의 미생물적 제조방법
JP2003528576A5 (zh)	2004-12-24
UA73493C2 (en)	2005-08-15	A microbiological process for the preparation of pravastatin and biologically pure culture mortierella maculata, being used in this process
EP1491522A1 (en)	2004-12-29	Microbial process for preparing pravastatin
CA2572473A1 (en)	2000-08-10	Sodium salt of pravastatin in crystalline form
HK1072050A (zh)	2005-08-12	降血脂剂治疗剂普伐他汀的微生物制程
AU2004218684A1 (en)	2004-10-28	Microbial process for preparing pravastatin
HU225936B1 (en)	2008-01-28	Hydroxylation of compactin to pravastatin by micromonospora
HU219821B (hu)	2001-08-28	Eljárás laktonszármazékok előállítására