JPH0437826B2 - - Google Patents

Info

Publication number: JPH0437826B2
Authority: JP; Japan
Prior art keywords: spagarin; acid; general formula; methanol; hydrochloride
Prior art date: 1982-08-10
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

Application number

JP13802182A

Other languages

English (en)

Japanese (ja)

Other versions

JPS5929652A (ja

Inventor

Rinzo Nishizawa

Masao Suzuki

Masao Takei

Masao Yoshida

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Takara Shuzo Co Ltd

Nippon Kayaku Co Ltd

Original Assignee

Takara Shuzo Co Ltd

Nippon Kayaku Co 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.)

1982-08-10

Filing date

1982-08-10

Publication date

1992-06-22

1982-08-10 Application filed by Takara Shuzo Co Ltd, Nippon Kayaku Co Ltd filed Critical Takara Shuzo Co Ltd

1982-08-10 Priority to JP13802182A priority Critical patent/JPS5929652A/ja

1984-02-16 Publication of JPS5929652A publication Critical patent/JPS5929652A/ja

1992-06-22 Publication of JPH0437826B2 publication Critical patent/JPH0437826B2/ja

Status Granted legal-status Critical Current

Links

150000003839 salts Chemical class 0.000 claims description 32
239000002253 acid Substances 0.000 claims description 29
238000000034 method Methods 0.000 claims description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
239000003480 eluent Substances 0.000 claims description 16
229910017053 inorganic salt Inorganic materials 0.000 claims description 11
238000004440 column chromatography Methods 0.000 claims description 9
239000003960 organic solvent Substances 0.000 claims description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000001931 aliphatic group Chemical group 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
239000000463 material Substances 0.000 claims description 4
238000012856 packing Methods 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
239000000243 solution Substances 0.000 description 19
239000011780 sodium chloride Substances 0.000 description 17
239000000047 product Substances 0.000 description 15
150000001875 compounds Chemical class 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
-1 formyloxy group Chemical group 0.000 description 9
239000012535 impurity Substances 0.000 description 9
238000000746 purification Methods 0.000 description 9
229920005654 Sephadex Polymers 0.000 description 8
239000012507 Sephadex™ Substances 0.000 description 8
239000000203 mixture Substances 0.000 description 8
238000007796 conventional method Methods 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
239000007788 liquid Substances 0.000 description 5
239000002994 raw material Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000012043 crude product Substances 0.000 description 4
235000014113 dietary fatty acids Nutrition 0.000 description 4
239000003814 drug Substances 0.000 description 4
239000000194 fatty acid Substances 0.000 description 4
229930195729 fatty acid Natural products 0.000 description 4
HAXKLTHULHEENJ-UHFFFAOYSA-N n-[4-(3-aminopropylamino)butyl]-2,2-dihydroxyacetamide;dihydrochloride Chemical compound Cl.Cl.NCCCNCCCCNC(=O)C(O)O HAXKLTHULHEENJ-UHFFFAOYSA-N 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000012141 concentrate Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
238000010828 elution Methods 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000013076 target substance Substances 0.000 description 3
RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
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 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
238000011049 filling Methods 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
238000011084 recovery Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
230000008961 swelling Effects 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
JPBYXYFQKIDRAL-RGMNGODLSA-N (3s)-7-(diaminomethylideneamino)-3-hydroxyheptanamide;hydrochloride Chemical compound Cl.NC(=O)C[C@@H](O)CCCCNC(N)=N JPBYXYFQKIDRAL-RGMNGODLSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
FTUSVSFXDXMXGE-UHFFFAOYSA-N 7-(diaminomethylideneamino)heptanamide;hydrochloride Chemical compound Cl.NC(=N)NCCCCCCC(N)=O FTUSVSFXDXMXGE-UHFFFAOYSA-N 0.000 description 1
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
WZAOWTVQGPNMAB-QRPNPIFTSA-N [(3s)-1-amino-7-(diaminomethylideneamino)-1-oxoheptan-3-yl] acetate;hydrochloride Chemical class Cl.CC(=O)O[C@H](CC(N)=O)CCCCNC(N)=N WZAOWTVQGPNMAB-QRPNPIFTSA-N 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000001093 anti-cancer Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
238000009835 boiling Methods 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
150000001649 bromium compounds Chemical class 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
238000001035 drying Methods 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
244000005700 microbiome Species 0.000 description 1
PYIZVKUBZVSTJN-UHFFFAOYSA-N n-[4-(3-aminopropylamino)butyl]-2,2-dihydroxyacetamide Chemical compound NCCCNCCCCNC(=O)C(O)O PYIZVKUBZVSTJN-UHFFFAOYSA-N 0.000 description 1
MXUVRZDNPMJFKO-UHFFFAOYSA-N n-[4-(3-aminopropylamino)butyl]-2,2-dihydroxyacetamide;hydrochloride Chemical compound Cl.NCCCNCCCCNC(=O)C(O)O MXUVRZDNPMJFKO-UHFFFAOYSA-N 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
150000007519 polyprotic acids Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
239000012264 purified product Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1

Landscapes

Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

JP13802182A 1982-08-10 1982-08-10 スパガリンまたはその誘導体の精製法 Granted JPS5929652A (ja)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
JP13802182A JPS5929652A (ja)	1982-08-10	1982-08-10	スパガリンまたはその誘導体の精製法

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP13802182A JPS5929652A (ja)	1982-08-10	1982-08-10	スパガリンまたはその誘導体の精製法

Publications (2)

Publication Number	Publication Date
JPS5929652A JPS5929652A (ja)	1984-02-16
JPH0437826B2 true JPH0437826B2 (zh)	1992-06-22

Family

ID=15212197

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP13802182A Granted JPS5929652A (ja)	1982-08-10	1982-08-10	スパガリンまたはその誘導体の精製法

Country Status (1)

Country	Link
JP (1)	JPS5929652A (zh)

1982
- 1982-08-10 JP JP13802182A patent/JPS5929652A/ja active Granted

Also Published As

Publication number	Publication date
JPS5929652A (ja)	1984-02-16

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