JPS6192577A

JPS6192577A - 新規マクロライド抗生物質とその製法

新規マクロライド抗生物質とその製法

Info

Publication number: JPS6192577A
Authority: JP; Japan
Prior art keywords: antibiotic; reaction; medium; methanol; culture
Prior art date: 1985-09-20
Legal status : Granted

Application number

JP60206347A

Other languages

English (en)

Japanese (ja)

Other versions

JPS6326118B2 (enrdf_load_stackoverflow

Inventor

Masaru Kotani

小谷　勝

Shuzo Satoi

里井　秀三

Naoki Muto

武藤　直紀

Satoru Saito

哲斉藤

Current Assignee

Toyo Jozo KK

Original Assignee

Toyo Jozo KK

Priority date

1985-09-20

Filing date

1985-09-20

Publication date

1986-05-10

1985-09-20 Application filed by Toyo Jozo KK filed Critical Toyo Jozo KK

1985-09-20 Priority to JP60206347A priority Critical patent/JPS6192577A/ja

1986-05-10 Publication of JPS6192577A publication Critical patent/JPS6192577A/ja

1988-05-27 Publication of JPS6326118B2 publication Critical patent/JPS6326118B2/ja

Status Granted legal-status Critical Current

Links

238000004519 manufacturing process Methods 0.000 title claims description 6
239000003120 macrolide antibiotic agent Substances 0.000 title abstract description 6
230000003115 biocidal effect Effects 0.000 claims abstract description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 18
239000000126 substance Substances 0.000 claims abstract description 14
229910052799 carbon Inorganic materials 0.000 claims abstract description 4
238000002844 melting Methods 0.000 claims abstract description 3
230000008018 melting Effects 0.000 claims abstract description 3
QABCJBNUVVMWAL-HXRJSAKRSA-N (2e,5r,7s,8s,9s,10e,14r,15r)-8-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-15-[[(2r,3r,4r,5r,6r)-5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl]oxymethyl]-5,7,9-trimethyl-13,17-dioxabicyclo[14.1.0]heptadeca-2,10-diene-4,12-dione Chemical compound O([C@@H]1[C@@H](C)/C=C/C(=O)O[C@@H]([C@H](C2OC2/C=C/C(=O)[C@H](C)C[C@@H]1C)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@@H]1O[C@H](C)C[C@H](N(C)C)[C@H]1O QABCJBNUVVMWAL-HXRJSAKRSA-N 0.000 claims abstract 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
238000006243 chemical reaction Methods 0.000 claims description 8
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
241000187708 Micromonospora Species 0.000 claims description 6
238000000862 absorption spectrum Methods 0.000 claims description 5
239000000843 powder Substances 0.000 claims description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
239000002253 acid Substances 0.000 claims description 3
238000012258 culturing Methods 0.000 claims description 3
150000003839 salts Chemical class 0.000 claims description 3
241000894006 Bacteria Species 0.000 claims description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
230000002378 acidificating effect Effects 0.000 claims description 2
150000007513 acids Chemical class 0.000 claims description 2
238000004042 decolorization Methods 0.000 claims description 2
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 claims description 2
229910052757 nitrogen Inorganic materials 0.000 claims description 2
239000012286 potassium permanganate Substances 0.000 claims description 2
238000005481 NMR spectroscopy Methods 0.000 claims 1
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 abstract description 12
239000003960 organic solvent Substances 0.000 abstract description 9
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 abstract description 8
238000000034 method Methods 0.000 abstract description 7
239000002904 solvent Substances 0.000 abstract description 5
229920001353 Dextrin Polymers 0.000 abstract description 4
239000004375 Dextrin Substances 0.000 abstract description 4
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 abstract description 4
241001465754 Metazoa Species 0.000 abstract description 4
239000003242 anti bacterial agent Substances 0.000 abstract description 4
229910000019 calcium carbonate Inorganic materials 0.000 abstract description 4
235000019425 dextrin Nutrition 0.000 abstract description 4
239000008103 glucose Substances 0.000 abstract description 4
239000007787 solid Substances 0.000 abstract description 4
229940041514 candida albicans extract Drugs 0.000 abstract description 3
-1 casin hydrolyzate Substances 0.000 abstract description 3
239000012138 yeast extract Substances 0.000 abstract description 3
238000004440 column chromatography Methods 0.000 abstract description 2
239000000463 material Substances 0.000 abstract 3
208000035473 Communicable disease Diseases 0.000 abstract 1
241000233866 Fungi Species 0.000 abstract 1
241001134671 Micromonospora griseorubida Species 0.000 abstract 1
235000010216 calcium carbonate Nutrition 0.000 abstract 1
239000000706 filtrate Substances 0.000 abstract 1
239000002609 medium Substances 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
239000000284 extract Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
239000000047 product Substances 0.000 description 4
239000000243 solution Substances 0.000 description 4
244000068988 Glycine max Species 0.000 description 3
235000010469 Glycine max Nutrition 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
238000013019 agitation Methods 0.000 description 3
230000000844 anti-bacterial effect Effects 0.000 description 3
230000001580 bacterial effect Effects 0.000 description 3
238000012136 culture method Methods 0.000 description 3
235000013312 flour Nutrition 0.000 description 3
239000012533 medium component Substances 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
206010057190 Respiratory tract infections Diseases 0.000 description 2
241000191940 Staphylococcus Species 0.000 description 2
238000005273 aeration Methods 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000005018 casein Substances 0.000 description 2
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 description 2
235000021240 caseins Nutrition 0.000 description 2
239000012043 crude product Substances 0.000 description 2
238000010586 diagram Methods 0.000 description 2
238000001035 drying Methods 0.000 description 2
239000000203 mixture Substances 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
YRMCBQLZVBXOSJ-PCFSSPOYSA-N (e)-3-[(6r,6as)-4-hydroxy-6-methoxy-3-methyl-11-oxo-5,6,6a,7-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]prop-2-enamide Chemical compound CO[C@H]1NC2=C(O)C(C)=CC=C2C(=O)N2C=C(\C=C\C(N)=O)C[C@@H]12 YRMCBQLZVBXOSJ-PCFSSPOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
241000193830 Bacillus <bacterium> Species 0.000 description 1
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
ZOYWWAGVGBSJDL-UHFFFAOYSA-N D-desosamine Natural products CC1CC(N(C)C)C(O)C(O)O1 ZOYWWAGVGBSJDL-UHFFFAOYSA-N 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
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
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
235000009754 Vitis X bourquina Nutrition 0.000 description 1
235000012333 Vitis X labruscana Nutrition 0.000 description 1
240000006365 Vitis vinifera Species 0.000 description 1
235000014787 Vitis vinifera Nutrition 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
238000002814 agar dilution Methods 0.000 description 1
125000003172 aldehyde group Chemical group 0.000 description 1
239000012670 alkaline solution Substances 0.000 description 1
229940072049 amyl acetate Drugs 0.000 description 1
PGMYKACGEOXYJE-UHFFFAOYSA-N anhydrous amyl acetate Natural products CCCCCOC(C)=O PGMYKACGEOXYJE-UHFFFAOYSA-N 0.000 description 1
239000003674 animal food additive Substances 0.000 description 1
239000010775 animal oil Substances 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000002585 base Substances 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000010941 cobalt Substances 0.000 description 1
229910017052 cobalt Inorganic materials 0.000 description 1
GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
239000000306 component Substances 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000013058 crude material Substances 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
VTJCSBJRQLZNHE-CSMHCCOUSA-N desosamine Chemical compound C[C@@H](O)C[C@H](N(C)C)[C@@H](O)C=O VTJCSBJRQLZNHE-CSMHCCOUSA-N 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
238000000855 fermentation Methods 0.000 description 1
230000004151 fermentation Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000005187 foaming Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
235000012054 meals Nutrition 0.000 description 1
235000013372 meat Nutrition 0.000 description 1
244000005700 microbiome Species 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
235000013379 molasses Nutrition 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
235000011118 potassium hydroxide Nutrition 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000011121 sodium hydroxide Nutrition 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1