JPS6254476B2 - - Google Patents
Info
- Publication number
- JPS6254476B2 JPS6254476B2 JP12438580A JP12438580A JPS6254476B2 JP S6254476 B2 JPS6254476 B2 JP S6254476B2 JP 12438580 A JP12438580 A JP 12438580A JP 12438580 A JP12438580 A JP 12438580A JP S6254476 B2 JPS6254476 B2 JP S6254476B2
- Authority
- JP
- Japan
- Prior art keywords
- lactone
- formula
- isom
- compound
- ifo
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- -1 ML-236B lactone Chemical class 0.000 claims description 40
- 150000002596 lactones Chemical group 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 14
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical class 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 14
- 239000000284 extract Substances 0.000 claims description 11
- 244000005700 microbiome Species 0.000 claims description 11
- 229910052783 alkali metal Inorganic materials 0.000 claims description 9
- 125000005907 alkyl ester group Chemical group 0.000 claims description 9
- 108090000790 Enzymes Proteins 0.000 claims description 6
- 102000004190 Enzymes Human genes 0.000 claims description 6
- 241000187747 Streptomyces Species 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 241000235389 Absidia Species 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 238000000862 absorption spectrum Methods 0.000 description 18
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 16
- 238000004809 thin layer chromatography Methods 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 150000004702 methyl esters Chemical class 0.000 description 13
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 241000813867 Streptomyces roseochromogenus Species 0.000 description 11
- 159000000000 sodium salts Chemical class 0.000 description 11
- 241001061260 Emmelichthys struhsakeri Species 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 235000012000 cholesterol Nutrition 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 5
- 241000235555 Cunninghamella Species 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000010409 thin film Substances 0.000 description 4
- 241000293029 Absidia caerulea Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000593945 Streptomyces platensis Species 0.000 description 3
- 241000736855 Syncephalastrum racemosum Species 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 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 description 2
- 239000001888 Peptone Substances 0.000 description 2
- 108010080698 Peptones Proteins 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000012084 conversion product Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000013028 medium composition Substances 0.000 description 2
- 235000019319 peptone Nutrition 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000012521 purified sample Substances 0.000 description 2
- 238000006884 silylation reaction Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 1
- 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 241001290628 Cunninghamella echinulata Species 0.000 description 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 241000228143 Penicillium Species 0.000 description 1
- 235000002233 Penicillium roqueforti Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000971004 Streptomyces fulvissimus Species 0.000 description 1
- 241000187216 Streptomyces halstedii Species 0.000 description 1
- 241000736854 Syncephalastrum Species 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Priority Applications (23)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12438580A JPS5750894A (en) | 1980-09-08 | 1980-09-08 | Preparation of ml-236b derivative |
| DK247081A DK149080C (da) | 1980-06-06 | 1981-06-04 | Fremgangsmaade til fremstilling af derivater af ml-236b-carboxylsyre |
| MX819478U MX7065E (es) | 1980-06-06 | 1981-06-04 | Un procedimiento microbiologico para preparar derivados de ml-236b |
| DE19813122499 DE3122499A1 (de) | 1980-06-06 | 1981-06-05 | Neue derivate von ml-236b, verfahren zu ihrer herstellung und diese derivate enthaltende arzneimittelzubereitungen |
| IE1257/81A IE51270B1 (en) | 1980-06-06 | 1981-06-05 | Ml-236b derivatives and their preparation |
| IT67777/81A IT1144598B (it) | 1980-06-06 | 1981-06-05 | Composti farmaceutici atti ad inibire la biosintesi del colesterolo e procedimento per la loro preparazione |
| FR8111190A FR2483912B1 (fr) | 1980-06-06 | 1981-06-05 | Derives hydroxycarboxyles du compose ml-236b, leur procede de preparation et leur application therapeutique |
| KR1019810002023A KR840001055B1 (ko) | 1980-06-06 | 1981-06-05 | Ml-236b 유도체의 제조방법 |
| CH3722/81A CH655090A5 (de) | 1980-06-06 | 1981-06-05 | Hexahydronaphthalinderivate und ihre herstellung. |
| US06/270,846 US4346227A (en) | 1980-06-06 | 1981-06-05 | ML-236B Derivatives and their preparation |
| AU71376/81A AU549988B2 (en) | 1980-06-06 | 1981-06-05 | Hydroxy esters |
| FI811762A FI71168C (fi) | 1980-06-06 | 1981-06-05 | Foerfarande foer framstaellning av ml-236b-derivat vilka anvaends som laekemedel |
| ES502827A ES8300353A1 (es) | 1980-06-06 | 1981-06-05 | Procedimiento de preparar acidos hidroxicarboxilicos y sus derivados. |
| NL8102737A NL191738C (nl) | 1980-06-06 | 1981-06-05 | ML-236B-derivaten, werkwijze voor hun bereiding en farmaceutische preparaten, die deze derivaten bevatten. |
| SE8103560A SE453389B (sv) | 1980-06-06 | 1981-06-05 | Hydroxikarboxylsyror, ringslutna laktoner, salter och estrar derav samt forfarande for framstellning av nemnda foreningar |
| GB8117450A GB2077264B (en) | 1980-06-06 | 1981-06-08 | Ml-236b derivatives and their preparation |
| CA000379232A CA1150170A (en) | 1980-06-06 | 1981-06-08 | Ml-236b derivatives and their preparation |
| AT0256781A AT374495B (de) | 1980-06-06 | 1981-06-09 | Verfahren zur herstellung neuer derivate der verbindung ml-236b |
| BE0/205046A BE889150A (fr) | 1980-06-06 | 1981-06-09 | Derives hydroxycarboxyles du compose ml-236b, leur procede de preparation et leur application therapeutique |
| US06/351,975 US4448979A (en) | 1980-06-06 | 1982-02-24 | ML-236B Derivatives |
| US06/351,974 US4410629A (en) | 1980-06-06 | 1982-02-24 | ML-236B Derivatives and their preparation |
| MX9203563A MX9203563A (es) | 1980-06-06 | 1992-06-26 | Derivados de ml-236b y su preparacion. |
| NL960028C NL960028I2 (nl) | 1980-06-06 | 1996-11-18 | ML-236B-derivaten, werkwijze voor hun bereiding enfarmaceutische preparaten, die deze derivaten bevatten. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12438580A JPS5750894A (en) | 1980-09-08 | 1980-09-08 | Preparation of ml-236b derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5750894A JPS5750894A (en) | 1982-03-25 |
| JPS6254476B2 true JPS6254476B2 (sv) | 1987-11-16 |
Family
ID=14884092
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12438580A Granted JPS5750894A (en) | 1980-06-06 | 1980-09-08 | Preparation of ml-236b derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5750894A (sv) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010041619A1 (ja) | 2008-10-06 | 2010-04-15 | メルシャン株式会社 | シュードノカルディア・オートトロフィカ（Pseudonocardia autotrophica）発現ベクター |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUP0105000A3 (en) | 1999-01-20 | 2004-03-01 | Kyowa Hakko Kogyo Kk | Process for producing hmg-coa reductase inhibitors |
| WO2000044886A1 (fr) | 1999-01-29 | 2000-08-03 | Kyowa Hakko Kogyo Co., Ltd. | TECHNIQUE DE PRODUCTION D'INHIBITEUR DE HMG-CoA REDUCTASE |
| WO2007063866A1 (ja) | 2005-11-29 | 2007-06-07 | Kyowa Hakko Kogyo Co., Ltd. | 新規蛋白質および該蛋白質をコードするｄｎａ |
-
1980
- 1980-09-08 JP JP12438580A patent/JPS5750894A/ja active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010041619A1 (ja) | 2008-10-06 | 2010-04-15 | メルシャン株式会社 | シュードノカルディア・オートトロフィカ（Pseudonocardia autotrophica）発現ベクター |
| US9006412B2 (en) | 2008-10-06 | 2015-04-14 | Microbiopharm Japan Co., Ltd. | Expression vector for pseudonocardia autotrophica |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5750894A (en) | 1982-03-25 |
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