CA1092999A - Method for producing maytansinol and its derivatives - Google Patents

Method for producing maytansinol and its derivatives

Info

Publication number: CA1092999A
Authority: CA; Canada
Prior art keywords: maytansinol; volume; parts; maytanacine; propionate
Prior art date: 1977-03-31
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

CA288,732A

Other languages

English (en)

French (fr)

Inventor

Eiji Higashide

Mitsuko Asai

Seiichi Tanida

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.)

Takeda Pharmaceutical Co Ltd

Original Assignee

Takeda Chemical Industries 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.)

1977-03-31

Filing date

1977-10-14

Publication date

1981-01-06

1977-10-14 Application filed by Takeda Chemical Industries Ltd filed Critical Takeda Chemical Industries Ltd

1981-01-06 Application granted granted Critical

1981-01-06 Publication of CA1092999A publication Critical patent/CA1092999A/en

Status Expired legal-status Critical Current

Links

QWPXBEHQFHACTK-UHFFFAOYSA-N Maytansinol Natural products CN1C(=O)CC(O)C2(C)OC2C(C)C(OC(=O)N2)CC2(O)C(OC)C=CC=C(C)CC2=CC(OC)=C(Cl)C1=C2 QWPXBEHQFHACTK-UHFFFAOYSA-N 0.000 title claims abstract description 37
QWPXBEHQFHACTK-KZVYIGENSA-N (10e,12e)-86-chloro-12,14,4-trihydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-15,16-dihydro-14h-7-aza-1(6,4)-oxazina-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-6-one Chemical compound CN1C(=O)CC(O)C2(C)OC2C(C)C(OC(=O)N2)CC2(O)C(OC)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 QWPXBEHQFHACTK-KZVYIGENSA-N 0.000 title claims abstract description 36
238000004519 manufacturing process Methods 0.000 title abstract description 6
DGBBXVWXOHSLTG-UMDRASRXSA-N ansamitocin p 2 Chemical compound C([C@@H]([C@@]1(O[C@H]1[C@@H]1C)C)OC(=O)CC)C(=O)N(C)C(C(=C(OC)C=2)Cl)=CC=2C\C(C)=C\C=C\[C@@H](OC)[C@]2(O)NC(=O)O[C@H]1C2 DGBBXVWXOHSLTG-UMDRASRXSA-N 0.000 claims abstract description 36
MQYZCKOGTWYJAZ-UHFFFAOYSA-N ansamitocin P1 Natural products CN1C(=O)CC(OC(C)=O)C2(C)OC2C(C)C(OC(=O)N2)CC2(O)C(OC)C=CC=C(C)CC2=CC(OC)=C(Cl)C1=C2 MQYZCKOGTWYJAZ-UHFFFAOYSA-N 0.000 claims abstract description 33
244000005700 microbiome Species 0.000 claims abstract description 16
241000187654 Nocardia Species 0.000 claims abstract description 9
238000000034 method Methods 0.000 claims description 31
239000000203 mixture Substances 0.000 claims description 13
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 8
239000001963 growth medium Substances 0.000 claims description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 3
150000001875 compounds Chemical class 0.000 abstract description 10
239000002246 antineoplastic agent Substances 0.000 abstract description 2
QWPXBEHQFHACTK-RZKXNLMUSA-N CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)[C@@H](C)[C@@H]1O[C@@]1(C)[C@@H](O)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 Chemical compound CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)[C@@H](C)[C@@H]1O[C@@]1(C)[C@@H](O)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 QWPXBEHQFHACTK-RZKXNLMUSA-N 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 88
239000002609 medium Substances 0.000 description 20
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 17
239000000706 filtrate Substances 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
239000000741 silica gel Substances 0.000 description 14
229910002027 silica gel Inorganic materials 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
239000012043 crude product Substances 0.000 description 12
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
239000012141 concentrate Substances 0.000 description 9
235000008504 concentrate Nutrition 0.000 description 9
239000013078 crystal Substances 0.000 description 9
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 8
238000010828 elution Methods 0.000 description 8
238000011218 seed culture Methods 0.000 description 8
238000004809 thin layer chromatography Methods 0.000 description 8
229920001817 Agar Polymers 0.000 description 7
239000003463 adsorbent Substances 0.000 description 7
239000008272 agar Substances 0.000 description 7
239000003208 petroleum Substances 0.000 description 7
239000002904 solvent Substances 0.000 description 7
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
230000003115 biocidal effect Effects 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
238000000855 fermentation Methods 0.000 description 6
230000004151 fermentation Effects 0.000 description 6
239000000047 product Substances 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
239000000126 substance Substances 0.000 description 6
241000196324 Embryophyta Species 0.000 description 5
238000001914 filtration Methods 0.000 description 5
230000007935 neutral effect Effects 0.000 description 5
238000000746 purification Methods 0.000 description 5
239000011347 resin Substances 0.000 description 5
229920005989 resin Polymers 0.000 description 5
238000000638 solvent extraction Methods 0.000 description 5
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 4
239000001888 Peptone Substances 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
238000005273 aeration Methods 0.000 description 4
238000013019 agitation Methods 0.000 description 4
238000003556 assay Methods 0.000 description 4
229940041514 candida albicans extract Drugs 0.000 description 4
238000000354 decomposition reaction Methods 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
239000000284 extract Substances 0.000 description 4
239000008103 glucose Substances 0.000 description 4
239000002054 inoculum Substances 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
239000007788 liquid Substances 0.000 description 4
239000000049 pigment Substances 0.000 description 4
241000894007 species Species 0.000 description 4
229910001220 stainless steel Inorganic materials 0.000 description 4
239000010935 stainless steel Substances 0.000 description 4
239000008107 starch Substances 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
239000012138 yeast extract Substances 0.000 description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
108010080698 Peptones Proteins 0.000 description 3
240000004808 Saccharomyces cerevisiae Species 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
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 3
240000008042 Zea mays Species 0.000 description 3
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
235000002017 Zea mays subsp mays Nutrition 0.000 description 3
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 3
235000005822 corn Nutrition 0.000 description 3
238000001514 detection method Methods 0.000 description 3
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000000605 extraction Methods 0.000 description 3
239000012634 fragment Substances 0.000 description 3
238000011534 incubation Methods 0.000 description 3
229910052742 iron Inorganic materials 0.000 description 3
-1 manni~ol Chemical compound 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
235000019319 peptone Nutrition 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
238000000926 separation method Methods 0.000 description 3
239000000243 solution Substances 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
244000068988 Glycine max Species 0.000 description 2
235000010469 Glycine max Nutrition 0.000 description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
241000248418 Tetrahymena pyriformis Species 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
230000000259 anti-tumor effect Effects 0.000 description 2
229940088710 antibiotic agent Drugs 0.000 description 2
PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 2
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
239000007640 basal medium Substances 0.000 description 2
229910000019 calcium carbonate Inorganic materials 0.000 description 2
239000005018 casein Substances 0.000 description 2
BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical group 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
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238000011161 development Methods 0.000 description 2
239000003925 fat Substances 0.000 description 2
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FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical group O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
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235000015097 nutrients Nutrition 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 2
239000000523 sample Substances 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000002689 soil Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
238000011282 treatment Methods 0.000 description 2
HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
GMKMEZVLHJARHF-UHFFFAOYSA-N (2R,6R)-form-2.6-Diaminoheptanedioic acid Natural products OC(=O)C(N)CCCC(N)C(O)=O GMKMEZVLHJARHF-UHFFFAOYSA-N 0.000 description 1
PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
NOIRDLRUNWIUMX-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one;6-amino-1h-pyrimidin-2-one Chemical compound NC=1C=CNC(=O)N=1.O=C1NC(N)=NC2=C1NC=N2 NOIRDLRUNWIUMX-UHFFFAOYSA-N 0.000 description 1
241000186361 Actinobacteria <class> Species 0.000 description 1
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QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
235000005881 Calendula officinalis Nutrition 0.000 description 1
241000282836 Camelus dromedarius Species 0.000 description 1
SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 1
108010016626 Dipeptides Proteins 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
238000003794 Gram staining Methods 0.000 description 1
UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-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
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
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GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
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NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
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238000010521 absorption reaction Methods 0.000 description 1
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150000001298 alcohols Chemical class 0.000 description 1
PNNNRSAQSRJVSB-BXKVDMCESA-N aldehydo-L-rhamnose Chemical compound C[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)C=O PNNNRSAQSRJVSB-BXKVDMCESA-N 0.000 description 1
239000003513 alkali Substances 0.000 description 1
HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
229940072049 amyl acetate Drugs 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
PGMYKACGEOXYJE-UHFFFAOYSA-N anhydrous amyl acetate Natural products CCCCCOC(C)=O PGMYKACGEOXYJE-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
DLRVVLDZNNYCBX-ZZFZYMBESA-N beta-melibiose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)O1 DLRVVLDZNNYCBX-ZZFZYMBESA-N 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
239000000872 buffer Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
OLOZVPHKXALCRI-UHFFFAOYSA-L calcium malate Chemical compound [Ca+2].[O-]C(=O)C(O)CC([O-])=O OLOZVPHKXALCRI-UHFFFAOYSA-L 0.000 description 1
229940016114 calcium malate Drugs 0.000 description 1
239000001362 calcium malate Substances 0.000 description 1
235000011038 calcium malates Nutrition 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
238000005345 coagulation Methods 0.000 description 1
230000015271 coagulation Effects 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000000470 constituent Substances 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
239000012531 culture fluid Substances 0.000 description 1
FYGDTMLNYKFZSV-MRCIVHHJSA-N dextrin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1O[C@@H]1[C@@H](CO)OC(O[C@@H]2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-MRCIVHHJSA-N 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
235000013312 flour Nutrition 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
238000003306 harvesting Methods 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000012535 impurity Substances 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
239000010699 lard oil Substances 0.000 description 1
239000004325 lysozyme Substances 0.000 description 1
235000010335 lysozyme Nutrition 0.000 description 1
229960000274 lysozyme Drugs 0.000 description 1
WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical class [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
235000010355 mannitol Nutrition 0.000 description 1
235000013372 meat Nutrition 0.000 description 1
GMKMEZVLHJARHF-SYDPRGILSA-N meso-2,6-diaminopimelic acid Chemical compound [O-]C(=O)[C@@H]([NH3+])CCC[C@@H]([NH3+])C([O-])=O GMKMEZVLHJARHF-SYDPRGILSA-N 0.000 description 1
230000002906 microbiologic effect Effects 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
235000013379 molasses Nutrition 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
AADMRFXTAGXWSE-UHFFFAOYSA-N monoacetoxyscirpenol Natural products CC(=O)OC1C(O)C2OC3(C)C=C(C)CCC3(CO)C1(C)C24CO4 AADMRFXTAGXWSE-UHFFFAOYSA-N 0.000 description 1
230000000877 morphologic effect Effects 0.000 description 1
231100000219 mutagenic Toxicity 0.000 description 1
239000003471 mutagenic agent Substances 0.000 description 1
231100000707 mutagenic chemical Toxicity 0.000 description 1
230000035772 mutation Effects 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
239000012454 non-polar solvent Substances 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
239000006916 nutrient agar Substances 0.000 description 1
239000006877 oatmeal agar Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
238000010298 pulverizing process Methods 0.000 description 1
MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
238000011160 research Methods 0.000 description 1
239000012488 sample solution Substances 0.000 description 1
238000005070 sampling Methods 0.000 description 1
238000012216 screening Methods 0.000 description 1
CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000004455 soybean meal Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000009897 systematic effect Effects 0.000 description 1
238000012360 testing method Methods 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
241001446247 uncultured actinomycete Species 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
- C12P17/188—Heterocyclic compound containing in the condensed system at least one hetero ring having nitrogen atoms and oxygen atoms as the only ring heteroatoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Zoology (AREA)
Wood Science & Technology (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Biotechnology (AREA)
Microbiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Biochemistry (AREA)
Public Health (AREA)
General Engineering & Computer Science (AREA)
Genetics & Genomics (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Compounds Of Unknown Constitution (AREA)

CA288,732A 1977-03-31 1977-10-14 Method for producing maytansinol and its derivatives Expired CA1092999A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP37167/1977		1977-03-31
JP52037167A JPS6010718B2 (ja)	1977-03-31	1977-03-31	メイタンシノ−ル，メイタナシンおよびメイタンシノ−ル・プロピオネ−トの製造法

Publications (1)

Publication Number	Publication Date
CA1092999A true CA1092999A (en)	1981-01-06

Family

ID=12490032

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA288,732A Expired CA1092999A (en)	1977-03-31	1977-10-14	Method for producing maytansinol and its derivatives

Country Status (20)

Country	Link
JP (1)	JPS6010718B2 (pl)
AT (1)	AT362058B (pl)
AU (1)	AU507869B2 (pl)
CA (1)	CA1092999A (pl)
CH (1)	CH631740A5 (pl)
CS (1)	CS214881B2 (pl)
DE (1)	DE2746253C2 (pl)
DK (1)	DK143570C (pl)
ES (1)	ES463206A1 (pl)
FR (1)	FR2385798A1 (pl)
GB (1)	GB1554395A (pl)
HU (1)	HU177391B (pl)
IE (1)	IE45888B1 (pl)
IT (1)	IT1094003B (pl)
NL (1)	NL7711273A (pl)
PL (1)	PL108863B1 (pl)
PT (1)	PT67853B (pl)
SE (1)	SE7711543L (pl)
SU (1)	SU938746A3 (pl)
YU (1)	YU243777A (pl)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS6010720B2 (ja) *	1977-11-18	1985-03-19	武田薬品工業株式会社	抗生物質ｃ―１５００３ｐ―４の製造法
JPS6016236B2 (ja) *	1977-11-18	1985-04-24	武田薬品工業株式会社	抗生物質ｃ―１５００３ｐ―３の製造法
JPS55162791A (en) *	1979-06-05	1980-12-18	Takeda Chem Ind Ltd	Antibiotic c-15003pnd and its preparation
EP0028683A1 (en) *	1979-09-21	1981-05-20	Takeda Chemical Industries, Ltd.	Antibiotic C-15003 PHO and production thereof
US6573074B2 (en)	2000-04-12	2003-06-03	Smithkline Beecham Plc	Methods for ansamitocin production
US6333410B1 (en)	2000-08-18	2001-12-25	Immunogen, Inc.	Process for the preparation and purification of thiol-containing maytansinoids
US7432088B2 (en)	2003-05-08	2008-10-07	Immunogen Inc.	Methods for the production of ansamitocins
CN116239607B (zh) *	2023-01-04	2024-04-09	山东大学	一种美登素衍生物及其生物合成方法与应用

1977
- 1977-03-31 JP JP52037167A patent/JPS6010718B2/ja not_active Expired
- 1977-09-23 AU AU29073/77A patent/AU507869B2/en not_active Expired
- 1977-10-07 FR FR7730340A patent/FR2385798A1/fr active Granted
- 1977-10-07 SU SU772533351A patent/SU938746A3/ru active
- 1977-10-10 YU YU02437/77A patent/YU243777A/xx unknown
- 1977-10-13 SE SE7711543A patent/SE7711543L/ not_active Application Discontinuation
- 1977-10-13 NL NL7711273A patent/NL7711273A/xx not_active Application Discontinuation
- 1977-10-13 CS CS776677A patent/CS214881B2/cs unknown
- 1977-10-13 HU HU77TA1458A patent/HU177391B/hu unknown
- 1977-10-14 CH CH1260477A patent/CH631740A5/de not_active IP Right Cessation
- 1977-10-14 AT AT736377A patent/AT362058B/de not_active IP Right Cessation
- 1977-10-14 CA CA288,732A patent/CA1092999A/en not_active Expired
- 1977-10-14 ES ES463206A patent/ES463206A1/es not_active Expired
- 1977-10-14 DE DE2746253A patent/DE2746253C2/de not_active Expired
- 1977-10-14 GB GB42821/77A patent/GB1554395A/en not_active Expired
- 1977-10-14 DK DK458977A patent/DK143570C/da not_active IP Right Cessation
- 1977-10-14 IE IE2100/77A patent/IE45888B1/en unknown
- 1977-10-15 PL PL1977201539A patent/PL108863B1/pl not_active IP Right Cessation
1978
- 1978-03-30 PT PT67853A patent/PT67853B/pt unknown
- 1978-03-30 IT IT21819/78A patent/IT1094003B/it active

Also Published As

Publication number	Publication date
FR2385798B1 (pl)	1980-04-25
IT7821819A0 (it)	1978-03-30
DK458977A (da)	1978-10-01
HU177391B (en)	1981-09-28
AU2907377A (en)	1979-03-29
DE2746253A1 (de)	1978-10-05
IE45888L (en)	1978-09-30
PL201539A1 (pl)	1978-09-25
PT67853A (en)	1978-04-01
YU243777A (en)	1982-06-30
FR2385798A1 (fr)	1978-10-27
DE2746253C2 (de)	1986-08-21
NL7711273A (nl)	1978-10-03
CH631740A5 (en)	1982-08-31
ES463206A1 (es)	1978-08-16
IT1094003B (it)	1985-07-26
SU938746A3 (ru)	1982-06-23
SE7711543L (sv)	1978-10-01
CS214881B2 (en)	1982-06-25
JPS53121998A (en)	1978-10-24
AU507869B2 (en)	1980-02-28
JPS6010718B2 (ja)	1985-03-19
DK143570C (da)	1982-02-08
GB1554395A (en)	1979-10-17
AT362058B (de)	1981-04-27
IE45888B1 (en)	1982-12-29
ATA736377A (de)	1980-09-15
PT67853B (en)	1980-05-05
PL108863B1 (en)	1980-05-31
DK143570B (da)	1981-09-07

Legal Events

Date	Code	Title	Description
1998-01-06	MKEX	Expiry

Publication	Publication Date	Title
US4151042A (en)	1979-04-24	Method for producing maytansinol and its derivatives
US4162940A (en)	1979-07-31	Method for producing Antibiotic C-15003 by culturing nocardia
CA1131144A (en)	1982-09-07	Antibiotic c-15003 pnd
US4331598A (en)	1982-05-25	Maytansinoids
CA2012274A1 (en)	1990-09-15	New process for producing immunosuppressant agent
EP0031430B1 (en)	1983-12-28	A method for the production of antibiotic c-15003 p-3
US4187292A (en)	1980-02-05	Antibiotics produced from the microorganism nocardice
US4228239A (en)	1980-10-14	Method for producing antibiotic C-15003 P-3
CA1092999A (en)	1981-01-06	Method for producing maytansinol and its derivatives
CA1079213A (en)	1980-06-10	Antibiotic and processes for its manufacture
US4229533A (en)	1980-10-21	Method for producing antibiotic C-15003 P-4
US4550021A (en)	1985-10-29	Antitumor antibiotic 81-484 and process for its production
CA1107212A (en)	1981-08-18	Antibiotic c-15003
CA1152915A (en)	1983-08-30	Antibiotics c-14482 b.sub.1, b.sub.2 and b.sub.3
US3991183A (en)	1976-11-09	Antibiotic produced by a species of micromonospora
US5272068A (en)	1993-12-21	Process for producing immunosuppressant agent L-683942 by fermentation
CA1121814A (en)	1982-04-13	Antibiotic c-15003
GB1592264A (en)	1981-07-01	Treatment of tumor-carrying animal with antibiotic c-15003
US5283183A (en)	1994-02-01	Cyclic FR-900520 microbial biotransformation agent
CA1104078A (en)	1981-06-30	Antibiotics c-14919 e-1 and e-2
US3743635A (en)	1973-07-03	27-demethoxy-27-hydroxyrifamycin derivatives
KR810000510B1 (ko)	1981-05-25	메이탄시노올 유도체의 제조방법
US5268281A (en)	1993-12-07	Cyclic FR-900520 microbial biotransformation agent
KR810001056B1 (ko)	1981-09-07	항생물질 c-15003의 제조법
GB2185480A (en)	1987-07-22	Production of avermectins