RU95122661A - 1-N-Ethylgentamycin Derivatives and Methods for Their Production - Google Patents
1-N-Ethylgentamycin Derivatives and Methods for Their ProductionInfo
- Publication number
- RU95122661A RU95122661A RU95122661/13A RU95122661A RU95122661A RU 95122661 A RU95122661 A RU 95122661A RU 95122661/13 A RU95122661/13 A RU 95122661/13A RU 95122661 A RU95122661 A RU 95122661A RU 95122661 A RU95122661 A RU 95122661A
- Authority
- RU
- Russia
- Prior art keywords
- hydrogen
- gentamicin
- ethyl
- derivative
- formula
- Prior art date
Links
- 229910052739 hydrogen Inorganic materials 0.000 claims 8
- 239000001257 hydrogen Substances 0.000 claims 8
- 150000003839 salts Chemical class 0.000 claims 6
- 239000011780 sodium chloride Substances 0.000 claims 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 5
- VEGXETMJINRLTH-BOZYPMBZSA-N gentamycin C1a Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N VEGXETMJINRLTH-BOZYPMBZSA-N 0.000 claims 4
- 241000187722 Micromonospora echinospora Species 0.000 claims 3
- 125000003277 amino group Chemical group 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 239000000203 mixture Substances 0.000 claims 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 238000002360 preparation method Methods 0.000 claims 2
- 239000000725 suspension Substances 0.000 claims 2
- CEAZRRDELHUEMR-CAMVTXANSA-N (2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4,6-diamino-3-[(2R,3R,6S)-3-amino-6-[(1R)-1-(methylamino)ethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol Chemical compound O1[C@H]([C@@H](C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-CAMVTXANSA-N 0.000 claims 1
- XUFIWSHGXVLULG-IDLVJFIQSA-N (2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4,6-diamino-3-[(2R,3R,6S)-3-amino-6-[(1R)-1-aminoethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)[C@@H](C)N)N)[C@@H](N)C[C@H]1N XUFIWSHGXVLULG-IDLVJFIQSA-N 0.000 claims 1
- DNYGXMICFMACRA-XHEDQWPISA-N Gentamicin C2b Chemical compound O1[C@H](CNC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N DNYGXMICFMACRA-XHEDQWPISA-N 0.000 claims 1
- 229910013470 LiC1 Inorganic materials 0.000 claims 1
- 210000004940 Nucleus Anatomy 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- 238000007792 addition Methods 0.000 claims 1
- 239000000010 aprotic solvent Substances 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 230000003115 biocidal Effects 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000000605 extraction Methods 0.000 claims 1
- 238000000855 fermentation Methods 0.000 claims 1
- 230000004151 fermentation Effects 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 239000003456 ion exchange resin Substances 0.000 claims 1
- 229920003303 ion-exchange polymer Polymers 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 230000003505 mutagenic Effects 0.000 claims 1
- 231100000219 mutagenic Toxicity 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 239000003638 reducing agent Substances 0.000 claims 1
- 238000010187 selection method Methods 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
- 230000002194 synthesizing Effects 0.000 claims 1
- 229910052723 transition metal Inorganic materials 0.000 claims 1
- -1 transition metal acetate Chemical class 0.000 claims 1
Claims (10)
где R1, R2, R3, R4, R5 пpиведены в конце pаздела на с.133
или их солей, образованных добавлением кислот, причем методика способа предусматривает следующее:
(1) гентамицин C1, гентамицин C2, гентамицин C1a или гентамицин C2b растворяют в апротонном растворителе, затем аминогруппы за исключением аминогруппы в положении 1-N- защищают ацильной группой путем ацилирования в присутствии ацетата двухвалентного переходного металла,
(2) аминогруппу в положении 1-N этилируют ацетальдегидом в присутствии восстановителя;
(3) все защитные группы удаляют гидролизом;
(4) производное 1-N-этилгентамицина C выделяют в виде свободного основания или в виде соли, полученной в реакции с кислотой, отличающийся тем, что гентамицин C1a, применяемый в качестве исходного ядра в синтезе 1-N-этилгентамицина C1a, получают из ферментационного бульона мутанта Micromonospora echinospora CGMCC-0197 экстракцией ионообменной смолой.3. A method of obtaining a derivative of 1-N-ethylgentamicin with the formula
where R 1 , R 2 , R 3 , R 4 , R 5 are given at the end of the section on p.133
or their salts formed by the addition of acids, moreover, the methodology of the method provides for the following:
(1) gentamicin C 1 , gentamicin C 2 , gentamicin C 1a or gentamicin C 2b is dissolved in an aprotic solvent, then the amino groups with the exception of the amino group at the 1-N- position are protected by an acyl group by acylation in the presence of divalent transition metal acetate,
(2) the amino group at the 1-N position is ethylated with acetaldehyde in the presence of a reducing agent;
(3) all protecting groups are removed by hydrolysis;
(4) the 1-N-ethylgentamicin C is isolated as the free base or as a salt obtained by the reaction with an acid, characterized in that gentamicin C 1a, used as a starting nucleus in the synthesis of 1-N-ethylgentamicin C 1a, prepared from fermentation broth of the mutant Micromonospora echinospora CGMCC-0197 by extraction with an ion exchange resin.
где R3 и R4 - водород, R5 - этил, R1 и R2 (которые одинаковы или различны) - метил или водород, или его фармацевтически приемлемой солью.5. Semi-synthetic antibiotic, which is a derivative of 1-N-ethylgentamycin of the following General formula
where R 3 and R 4 are hydrogen, R 5 is ethyl, R 1 and R 2 (which are the same or different) are methyl or hydrogen, or a pharmaceutically acceptable salt thereof.
причем препарат содержит 0,01-99,99 мас.% активного компонента и 99,99 мас.% фармацевтически приемлемого носителя.8. A composition containing, as an active component, a 1-N-ethyl-gentamycin C derivative of the following general formula or a salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 are indicated on page 133
moreover, the preparation contains 0.01-99.99 wt.% the active ingredient and 99.99 wt.% pharmaceutically acceptable carrier.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN93112412A CN1040177C (en) | 1993-04-23 | 1993-04-23 | 1-N-ethyl gentamicin derivative and its preparing method |
CN93112312.3 | 1993-04-23 |
Publications (2)
Publication Number | Publication Date |
---|---|
RU95122661A true RU95122661A (en) | 1998-03-10 |
RU2180226C2 RU2180226C2 (en) | 2002-03-10 |
Family
ID=4990026
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
RU95122661/13A RU2180226C2 (en) | 1993-04-23 | 1994-04-23 | ANTIBACTERIAL COMPOSITION WITH 1-N-ETHYLGENTAMYCIN C1a |
Country Status (7)
Country | Link |
---|---|
US (1) | US5814488A (en) |
JP (1) | JP3578762B2 (en) |
CN (1) | CN1040177C (en) |
AU (1) | AU6644094A (en) |
GB (1) | GB2293383B (en) |
RU (1) | RU2180226C2 (en) |
WO (1) | WO1994025566A1 (en) |
Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040168978A1 (en) * | 2001-04-18 | 2004-09-02 | Gray Buddy Don | Method and apparatus for recirculating tangential separation system |
US7115399B2 (en) * | 2001-07-31 | 2006-10-03 | Allergan, Inc. | Pinna reflex assay |
US7794713B2 (en) | 2004-04-07 | 2010-09-14 | Lpath, Inc. | Compositions and methods for the treatment and prevention of hyperproliferative diseases |
US7862812B2 (en) | 2006-05-31 | 2011-01-04 | Lpath, Inc. | Methods for decreasing immune response and treating immune conditions |
CN101225093B (en) * | 2007-01-17 | 2011-04-27 | 山东轩竹医药科技有限公司 | Aminoglycoside derivatives |
TWI425947B (en) | 2007-11-21 | 2014-02-11 | Achaogen Inc | Antibacterial aminoglycoside analogs |
NZ591458A (en) * | 2008-09-18 | 2012-07-27 | Manu Chaudhary | Novel single unit carbapenem aminoglycoside formulations the aminoglycoside is etimicin |
WO2010132760A1 (en) | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial derivatives of tobramycin |
WO2010132765A2 (en) * | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial aminoglycoside analogs |
WO2010132759A1 (en) | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial derivatives of dibekacin |
CN101928310B (en) * | 2010-03-26 | 2012-09-05 | 常州方圆制药有限公司 | 3,2',6'-tri-N-acetyl gentamicin C1aprepn |
CN101928311B (en) * | 2010-03-26 | 2012-09-05 | 常州方圆制药有限公司 | Preparation method of 1-N-ethyl gentamicin Cla |
CN101928309B (en) * | 2010-03-26 | 2012-10-10 | 常州方圆制药有限公司 | 3,2',6'-tri-N-acetyl gentamicin C1asynthesis method |
CN101928312B (en) * | 2010-03-26 | 2012-10-17 | 常州方圆制药有限公司 | Preparation method of 1-N-ethyl gentamicin C1a sulfate |
CN102250166A (en) * | 2010-05-21 | 2011-11-23 | 江西济民可信集团有限公司 | Method for preparing Etimicin sulfate |
CN102432648B (en) * | 2010-09-29 | 2016-03-23 | 无锡济民可信山禾药业股份有限公司 | A kind of reactant takes off the method for cobalt and extraction |
CN102432645B (en) * | 2010-09-29 | 2016-03-23 | 无锡济民可信山禾药业股份有限公司 | A kind of purification process of Etimicin sulfate |
CN102432647B (en) * | 2010-09-29 | 2016-03-23 | 无锡济民可信山禾药业股份有限公司 | A kind of glucoside-containing component and extraction and separation method thereof |
CN102532215B (en) * | 2010-12-24 | 2015-07-22 | 无锡济民可信山禾药业股份有限公司 | Aminoglycosides antibiotics compound and extraction separation method thereof |
CN102443026B (en) * | 2011-10-26 | 2016-12-21 | 江西省药明扬海医药科技有限公司 | A kind of glucoside-containing component and extraction separation method thereof |
CN103193838B (en) * | 2012-01-06 | 2016-08-24 | 上海医药工业研究院 | The pseudo-polymorphic of Etimicin sulfate, its preparation method and application thereof |
CN102617665A (en) * | 2012-02-29 | 2012-08-01 | 常州方圆制药有限公司 | Method for separating etimicin by sulfonic acid type cation exchange resin |
CN103374047B (en) * | 2012-04-27 | 2016-05-11 | 无锡济民可信山禾药业股份有限公司 | A kind of highly purified 3,2 ", 6 " tri--N-acetyl group is celebrated large C1a alkali (P1) isolation and purification method |
CN103113430B (en) * | 2013-03-15 | 2014-11-12 | 齐鲁天和惠世制药有限公司 | Method for preparing etimicin sulfate |
CN103665068B (en) * | 2013-12-16 | 2016-01-13 | 无锡济民可信山禾药业股份有限公司 | A kind of 1-N-ethyl gentamicinC 1apreparation method |
CN103665069B (en) * | 2013-12-17 | 2016-05-11 | 无锡济民可信山禾药业股份有限公司 | A kind of glucoside-containing component and extraction separation method thereof |
CN105503972B (en) * | 2015-12-09 | 2018-05-29 | 无锡济民可信山禾药业股份有限公司 | One kind synthesizes 1-N- ethyl gentamicinCs by catalyst of heteropoly acid1aMethod |
CN105503973B (en) * | 2015-12-25 | 2018-06-08 | 无锡济民可信山禾药业股份有限公司 | A kind of glucoside-containing component and its extraction separation method |
CN105966566B (en) * | 2016-05-23 | 2017-10-27 | 哈尔滨工程大学 | Hydrofoil catamaran course heel control method and device |
CN107868111A (en) * | 2017-07-07 | 2018-04-03 | 朱孝云 | Antibacterial aminoglycoside analog derivative |
CN108003205B (en) * | 2017-12-22 | 2020-04-10 | 中国医药集团总公司四川抗菌素工业研究所 | Aminoglycoside derivative and preparation method and application thereof |
CN110066304B (en) * | 2019-05-25 | 2022-08-16 | 无锡济煜山禾药业股份有限公司 | Synthesis method of 1-N-ethyl micronomicin |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3091572A (en) * | 1962-07-16 | 1963-05-28 | Schering Corp | Gentamycin and method of production |
CH551965A (en) * | 1970-06-22 | 1974-07-31 | Scherico Ltd | PROCESS FOR PRODUCING ANTIBIOTICALLY ACTIVE COMPOUNDS. |
US4029882A (en) * | 1974-03-19 | 1977-06-14 | Schering Corporation | Selective acylation of the C-1 amino group of aminoglycoside antibiotics |
CH606076A5 (en) * | 1973-08-06 | 1978-10-13 | Scherico Ltd | |
US4063015A (en) * | 1973-08-27 | 1977-12-13 | Schering Corporation | Garamine and derivatives thereof |
US4002742A (en) * | 1974-03-19 | 1977-01-11 | Schering Corporation | 1-N-alkyl-4,6-di-(aminoglycosyl)-1,3-diaminocyclitols, methods for their manufacture, methods for their use as antibacterial agents, and compositions useful therefor |
US4044123A (en) * | 1975-05-02 | 1977-08-23 | Schering Corporation | 6'-N-alkyl-4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols, methods for their use as antibacterial agents and compositions useful therefor |
US4136254A (en) * | 1976-06-17 | 1979-01-23 | Schering Corporation | Process of selectively blocking amino functions in aminoglycosides using transition metal salts and intermediates used thereby |
US4230847A (en) * | 1976-06-17 | 1980-10-28 | Schering Corporation | Aminoglycoside antibiotic compounds |
US4268503A (en) * | 1978-09-14 | 1981-05-19 | Fujisawa Pharmaceutical Co., Ltd. | Antibacterial composition |
ES475393A1 (en) * | 1978-11-24 | 1979-04-01 | Pereira Da Luz Artur | Manufacture of aminoglycoside antibiotics |
US4387219A (en) * | 1979-11-13 | 1983-06-07 | Sterling Drug Inc. | 2-Hydroxy gentamicin compounds |
US4412068A (en) * | 1981-06-08 | 1983-10-25 | Sterling Drug Inc. | Novel compounds of the gentamicin class |
CN1008445B (en) * | 1986-12-03 | 1990-06-20 | 复旦大学 | Strain a2 with proper component ratio gentamycin and its selective culture |
DE3751871T4 (en) * | 1986-12-23 | 1998-03-26 | Liposome Co Inc | Liposomes containing guanidine aminoglycoside |
-
1993
- 1993-04-23 CN CN93112412A patent/CN1040177C/en not_active Expired - Lifetime
-
1994
- 1994-04-23 JP JP52371894A patent/JP3578762B2/en not_active Expired - Lifetime
- 1994-04-23 US US08/537,784 patent/US5814488A/en not_active Expired - Lifetime
- 1994-04-23 RU RU95122661/13A patent/RU2180226C2/en active
- 1994-04-23 WO PCT/CN1994/000029 patent/WO1994025566A1/en active Application Filing
- 1994-04-23 AU AU66440/94A patent/AU6644094A/en not_active Abandoned
- 1994-04-23 GB GB9521654A patent/GB2293383B/en not_active Expired - Lifetime
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU95122661A (en) | 1-N-Ethylgentamycin Derivatives and Methods for Their Production | |
GB1598704A (en) | 3-de-o-methylfortimicins | |
JPS5618996A (en) | Muramyldipeptide derivative | |
US4199572A (en) | N-Substituted amino glycoside compounds, their production, and their use as medicaments | |
US3997524A (en) | Process for the manufacture of 6'-N-alkyl derivatives of sisomicin and verdamicin; novel intermediates useful therein, and novel 6'-N-alkylverdamicins prepared thereby | |
US4139563A (en) | α-ACETYLENIC DERIVATIVES OF AMINES | |
PT82134A (en) | Process for the preparation of amino acid derivatives comprising the culturing of fr-900490 producing strain belonging to the genus discosia | |
DE2437160B2 (en) | 1-N-ethylsisomicin and salts, processes for their preparation and pharmaceutical preparations containing these compounds | |
HU194269B (en) | Process for producing new 20-amino-tylosine derivatives | |
JPS6347703B2 (en) | ||
HU205131B (en) | Process for producing dexylosyl derivatives of antibiotics of group bu-3608, as well as pharmaceutical compositions comprising such compounds | |
US5409918A (en) | Crystalline cephem acid addition salts and process for their preparation | |
CA2046861A1 (en) | K2p pro stabilisation | |
US4914028A (en) | Method of preparing beta-2',2'-difluoronucleosides | |
MX9602756A (en) | NOVEL HIGH ENANTIO-SELECTIVE PROCESS FOR PRODUCING PURE ENANTIOMERIC CYCLOPENTANE AND CYCLOPENTENE-'beta'-AMINO ACIDS. | |
EP0138708B1 (en) | Isoefrotomycin | |
JPS5488242A (en) | Novel derivative of fortimicin b and its preparation | |
DE3112124A1 (en) | NEW DERIVATIVES OF ISTAMYCIN A AND B AND METHOD FOR THE PRODUCTION THEREOF | |
US4129720A (en) | Aminoeverninomicin and derivatives thereof | |
US2607770A (en) | Streptomycyl amines and production thereof | |
HUT77090A (en) | Clavulanic acid salts with a diamino-ether, proces for their production and pharmaceutical compositions containing the same | |
BG51252A3 (en) | Method for netylmycin preparation | |
DE69903455D1 (en) | METHOD FOR THE PRODUCTION OF SUBSTITUTED PHTHALOCYANINE CARBONIC AMIDES AND SUBSTITUTED PHTHALOCYANINE CARBONIC AMIDS | |
EP0108455B1 (en) | Sparsomycin (sc-rs) derivative; pharmaceutical composition having anti-tumor activity | |
DE2543535A1 (en) | NEW DERIVATIVES OF KANAMYCIN B AND METHOD OF MANUFACTURING THE SAME |