CA1172191A - Methode de preparation de mycarasyltylactone - Google Patents

Methode de preparation de mycarasyltylactone

Info

Publication number: CA1172191A
Authority: CA; Canada
Prior art keywords: mycarosyltylactone; tylactone; medium; tylosin; small
Prior art date: 1980-07-29
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

CA000382663A

Other languages

English (en)

Inventor

Richard H. Baltz

Eugene T. Seno

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.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

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.)

1980-07-29

Filing date

1981-07-28

Publication date

1984-08-07

1981-07-28 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1984-08-07 Application granted granted Critical

1984-08-07 Publication of CA1172191A publication Critical patent/CA1172191A/fr

Status Expired legal-status Critical Current

Links

238000004519 manufacturing process Methods 0.000 title claims abstract description 15
YJSXTLYNFBFHAT-UHFFFAOYSA-N Protylonolide Natural products CCC1CC(C)C(=O)C=CC(C)=CC(C)C(CC)OC(=O)CC(O)C(C)C1O YJSXTLYNFBFHAT-UHFFFAOYSA-N 0.000 claims abstract description 52
YJSXTLYNFBFHAT-HJOMEYPASA-N tylactone Chemical compound CC[C@H]1C[C@@H](C)C(=O)\C=C\C(\C)=C\[C@H](C)[C@@H](CC)OC(=O)C[C@@H](O)[C@H](C)[C@H]1O YJSXTLYNFBFHAT-HJOMEYPASA-N 0.000 claims abstract description 52
244000005700 microbiome Species 0.000 claims abstract description 11
241000187438 Streptomyces fradiae Species 0.000 claims abstract description 9
238000010564 aerobic fermentation Methods 0.000 claims abstract description 5
238000000034 method Methods 0.000 claims description 24
238000000855 fermentation Methods 0.000 claims description 17
230000004151 fermentation Effects 0.000 claims description 16
150000001875 compounds Chemical class 0.000 claims description 11
239000001963 growth medium Substances 0.000 claims description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 3
150000003839 salts Chemical class 0.000 claims description 3
230000002378 acidificating effect Effects 0.000 claims description 2
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 31
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
239000004182 Tylosin Substances 0.000 description 25
229960004059 tylosin Drugs 0.000 description 25
229930194936 Tylosin Natural products 0.000 description 24
239000002609 medium Substances 0.000 description 24
WBPYTXDJUQJLPQ-VMXQISHHSA-N tylosin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 WBPYTXDJUQJLPQ-VMXQISHHSA-N 0.000 description 24
235000019375 tylosin Nutrition 0.000 description 24
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
229940093499 ethyl acetate Drugs 0.000 description 9
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
235000019439 ethyl acetate Nutrition 0.000 description 8
239000000203 mixture Substances 0.000 description 8
240000008042 Zea mays Species 0.000 description 7
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 7
235000002017 Zea mays subsp mays Nutrition 0.000 description 7
235000005822 corn Nutrition 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
229960001701 chloroform Drugs 0.000 description 5
-1 ethyl - Chemical class 0.000 description 5
239000003120 macrolide antibiotic agent Substances 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
239000003208 petroleum Substances 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
229960001866 silicon dioxide Drugs 0.000 description 5
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
238000001514 detection method Methods 0.000 description 4
239000002054 inoculum Substances 0.000 description 4
150000002500 ions Chemical class 0.000 description 4
235000012054 meals Nutrition 0.000 description 4
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
235000019733 Fish meal Nutrition 0.000 description 3
244000068988 Glycine max Species 0.000 description 3
235000010469 Glycine max Nutrition 0.000 description 3
238000000862 absorption spectrum Methods 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
239000013078 crystal Substances 0.000 description 3
239000004467 fishmeal Substances 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
235000012424 soybean oil Nutrition 0.000 description 3
239000003549 soybean oil Substances 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 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
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
MOQOOKGPCBQMCY-UHFFFAOYSA-N acetic acid;hexane Chemical compound CC(O)=O.CCCCCC MOQOOKGPCBQMCY-UHFFFAOYSA-N 0.000 description 2
239000002253 acid Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
230000001851 biosynthetic effect Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
229910000019 calcium carbonate Inorganic materials 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000008367 deionised water Substances 0.000 description 2
229910021641 deionized water Inorganic materials 0.000 description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
239000000284 extract Substances 0.000 description 2
238000005755 formation reaction Methods 0.000 description 2
235000001727 glucose Nutrition 0.000 description 2
239000008103 glucose Substances 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
150000002596 lactones Chemical class 0.000 description 2
239000000787 lecithin Substances 0.000 description 2
229940067606 lecithin Drugs 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000000155 melt Substances 0.000 description 2
239000003471 mutagenic agent Substances 0.000 description 2
231100000707 mutagenic chemical Toxicity 0.000 description 2
230000003505 mutagenic effect Effects 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000013587 production medium Substances 0.000 description 2
238000012807 shake-flask culturing Methods 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000007787 solid Substances 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
239000007921 spray Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
238000012360 testing method Methods 0.000 description 2
235000013619 trace mineral Nutrition 0.000 description 2
239000011573 trace mineral Substances 0.000 description 2
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
WTLKTXIHIHFSGU-UHFFFAOYSA-N 2-nitrosoguanidine Chemical compound NC(N)=NN=O WTLKTXIHIHFSGU-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
235000016068 Berberis vulgaris Nutrition 0.000 description 1
241000335053 Beta vulgaris Species 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
108010068370 Glutens Proteins 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
241000357437 Mola Species 0.000 description 1
241000364057 Peoria Species 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
235000019764 Soybean Meal Nutrition 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
241000187747 Streptomyces Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
229920013624 Tylac Polymers 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
235000016127 added sugars Nutrition 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
239000002518 antifoaming agent Substances 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
239000002962 chemical mutagen Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
239000000470 constituent Substances 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
238000012258 culturing Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000005187 foaming Methods 0.000 description 1
239000012634 fragment Substances 0.000 description 1
235000021312 gluten Nutrition 0.000 description 1
230000012010 growth Effects 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
229960000443 hydrochloric acid Drugs 0.000 description 1
235000011167 hydrochloric acid Nutrition 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
125000004435 hydrogen atom Chemical class [H]* 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
229910052742 iron Inorganic materials 0.000 description 1
238000002955 isolation Methods 0.000 description 1
238000002372 labelling Methods 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000000463 material Substances 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
235000013379 molasses Nutrition 0.000 description 1
238000002703 mutagenesis Methods 0.000 description 1
231100000350 mutagenesis Toxicity 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
238000010979 pH adjustment Methods 0.000 description 1
239000008188 pellet Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
229920001451 polypropylene glycol Polymers 0.000 description 1
239000000047 product Substances 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
238000012216 screening Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
239000004455 soybean meal Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
238000004448 titration Methods 0.000 description 1
238000000825 ultraviolet detection Methods 0.000 description 1
230000009105 vegetative growth Effects 0.000 description 1

Landscapes

Preparation Of Compounds By Using Micro-Organisms (AREA)

CA000382663A 1980-07-29 1981-07-28 Methode de preparation de mycarasyltylactone Expired CA1172191A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US17331380A	1980-07-29	1980-07-29
US173,313		1980-07-29

Publications (1)

Publication Number	Publication Date
CA1172191A true CA1172191A (fr)	1984-08-07

Family

ID=22631453

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000382663A Expired CA1172191A (fr)	1980-07-29	1981-07-28	Methode de preparation de mycarasyltylactone

Country Status (2)

Country	Link
CA (1)	CA1172191A (fr)
NZ (1)	NZ197869A (fr)

1981
- 1981-07-28 NZ NZ19786981A patent/NZ197869A/en unknown
- 1981-07-28 CA CA000382663A patent/CA1172191A/fr not_active Expired

Also Published As

Publication number	Publication date
NZ197869A (en)	1984-04-27

Legal Events

Date	Code	Title	Description
2001-08-07	MKEX	Expiry

Publication	Publication Date	Title
US4151042A (en)	1979-04-24	Method for producing maytansinol and its derivatives
EP0573628B1 (fr)	1999-01-20	Nouveaux composes a83543 et leur procede de production
US5227295A (en)	1993-07-13	Process for isolating A83543 and its components
US4299953A (en)	1981-11-10	Mycarosyltylactone
US4440857A (en)	1984-04-03	Process for preparing mycarosyltylactone
US4366247A (en)	1982-12-28	Process for preparing tylactone
CA1092999A (fr)	1981-01-06	Methode de production du maytansinol et de ses derives
US4283390A (en)	1981-08-11	Antibiotics and process for production thereof
JPS6254433B2 (fr)	1987-11-14
US5221625A (en)	1993-06-22	Cyclcic FR-900520 microbial biotransformation agent
CA1172191A (fr)	1984-08-07	Methode de preparation de mycarasyltylactone
US4385116A (en)	1983-05-24	Demethylmacrocin and process for its production
US4362881A (en)	1982-12-07	Tylactone
US5225338A (en)	1993-07-06	Microbial preparation of 13β-13-deoxy-22,23-dihydro avermectin-B1A/B1B aglycone
CA1211731A (fr)	1986-09-23	Derives de de(mycinosyloxy)tylosine
JPS6220984B2 (fr)	1987-05-11
EP0045205B1 (fr)	1984-10-03	Macrolides
US5304485A (en)	1994-04-19	Antibiotic producing microorganism
US4410628A (en)	1983-10-18	A-39183 Antibiotics and process for production thereof
US2970947A (en)	1961-02-07	Process of producing an antibiotic of the tetracycline series
US5283183A (en)	1994-02-01	Cyclic FR-900520 microbial biotransformation agent
CA1171869A (fr)	1984-07-31	Tylactone
EP0260964A2 (fr)	1988-03-23	Hapalindoles
JPH0625095B2 (ja)	1994-04-06	抗生物質ｓｆ−２４１５物質およびその製造法
US3986928A (en)	1976-10-19	Antibiotic a-32390 and process for preparation thereof