RU96103686A - Method of enzymatic synthesis of β-lactam antibiotics in the presence of an enzyme inhibitor - Google Patents
Method of enzymatic synthesis of β-lactam antibiotics in the presence of an enzyme inhibitorInfo
- Publication number
- RU96103686A RU96103686A RU96103686/13A RU96103686A RU96103686A RU 96103686 A RU96103686 A RU 96103686A RU 96103686/13 A RU96103686/13 A RU 96103686/13A RU 96103686 A RU96103686 A RU 96103686A RU 96103686 A RU96103686 A RU 96103686A
- Authority
- RU
- Russia
- Prior art keywords
- group
- formula
- inhibitor
- branched
- linear
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 5
- 239000003782 beta lactam antibiotic agent Substances 0.000 title 1
- 230000015572 biosynthetic process Effects 0.000 title 1
- 230000002255 enzymatic effect Effects 0.000 title 1
- 229940125532 enzyme inhibitor Drugs 0.000 title 1
- 239000002532 enzyme inhibitor Substances 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- 239000002132 β-lactam antibiotic Substances 0.000 title 1
- 229940124586 β-lactam antibiotics Drugs 0.000 title 1
- 239000003112 inhibitor Substances 0.000 claims 4
- 150000001408 amides Chemical class 0.000 claims 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 claims 1
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 claims 1
- HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 claims 1
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims 1
- 229930186147 Cephalosporin Natural products 0.000 claims 1
- ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 229930182555 Penicillin Natural products 0.000 claims 1
- 108010073038 Penicillin Amidase Proteins 0.000 claims 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- WWVKQTNONPWVEL-UHFFFAOYSA-N caffeic acid phenethyl ester Natural products C1=C(O)C(O)=CC=C1C=CC(=O)OCC1=CC=CC=C1 WWVKQTNONPWVEL-UHFFFAOYSA-N 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 229940124587 cephalosporin Drugs 0.000 claims 1
- 150000001780 cephalosporins Chemical class 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 229960002510 mandelic acid Drugs 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 229940049954 penicillin Drugs 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
Claims (4)
где X - S или СН2;
R - 6-членное необязательно замещенное углеводородное кольцо;
R1 атом водорода, атом галогена, метильная группа, метоксигруппа, С1 - С4-алкенильная группа или метиленовая группа, связанная с органическим радикалом атомами кислорода, серы или азота,
где 6-аминопенициллановая или 7-аминоцефалоспорановая кислота формулы IV или V
где X и R1 имеют указанные значения,
взаимодействует при температуре -5...+35oС в присутствии фермента пенициллинацилазы в свободной или иммобилизованной форме с амидом формулы III
где R имеет указанные значения;
R2 и R3 - каждый независимо атом водорода или линейная либо разветвленная С1 - С3-алкильная группа,
или с его солями, в молярном отношении 1 - 6 моль указанного амида формулы III на 1 моль кислоты формулы IV или V, отличающийся тем, что в реакционную смесь добавляют ингибитор фермента формулы VI
где R4 - линейная либо разветвленная С1 - С5 алкильная группа, замещенное или незамещенное ароматическое кольцо, галоген, протон;
Y может отсутствовать или, в случае присутствия, являться O, S, CH2, фенилом или галогеном;
R5 выбирается из числа карбоксильной группы, линейных либо разветвленных С1 - С4-эфиров или -CONH2-группы;
R6 выбирается из Н, ОН, ОСНО или СН3,
при этом ингибитор присутствует в молярной концентрации от 0,0001 до 0,5.1. The method of producing penicillin or cephalosporin of formula I or II
where X is S or CH 2 ;
R is a 6-membered optionally substituted hydrocarbon ring;
R 1 is a hydrogen atom, a halogen atom, a methyl group, a methoxy group, a C 1 - C 4 alkenyl group or a methylene group bound to an organic radical by oxygen atoms, sulfur or nitrogen,
Where 6-aminopenicillanic or 7-aminocephalosporanic acid of formula IV
where X and R 1 have the indicated meanings,
interacts at a temperature of -5 ... + 35 o C in the presence of the enzyme penicillin acylase in free or immobilized form with the amide of formula III
where R has the indicated meanings;
R 2 and R 3 are each independently a hydrogen atom or a linear or branched C 1 - C 3 alkyl group,
or with its salts, in a molar ratio of 1 to 6 mol of the indicated amide of formula III per 1 mol of the acid of formula IV or V, characterized in that an inhibitor of the enzyme of formula VI is added to the reaction mixture
where R 4 is a linear or branched C 1 - C 5 alkyl group, substituted or unsubstituted aromatic ring, halogen, proton;
Y may be absent or, if present, be O, S, CH 2 , phenyl or halogen;
R 5 is selected from the carboxyl group, linear or branched C 1 -C 4 esters or -CONH 2 groups;
R 6 is selected from H, OH, CABE or CH 3 ,
however, the inhibitor is present in a molar concentration of from 0.0001 to 0.5.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI95A000383 | 1995-02-28 | ||
| ITMI96A000033 | 1996-01-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU96103686A true RU96103686A (en) | 1998-05-10 |
Family
ID=
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2537845C2 (en) * | 2012-04-25 | 2015-01-10 | Федеральное государственное бюджетное образовательное учреждение высшего профессиональногообразования "Московский государственный университет имени М.В. Ломоносова " (МГУ) | Method of synthesising peptides, including beta-lactam antibiotics with application of penicillin acylase version |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2537845C2 (en) * | 2012-04-25 | 2015-01-10 | Федеральное государственное бюджетное образовательное учреждение высшего профессиональногообразования "Московский государственный университет имени М.В. Ломоносова " (МГУ) | Method of synthesising peptides, including beta-lactam antibiotics with application of penicillin acylase version |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69228627D1 (en) | Long chain carboximide ester | |
| RU2002109387A (en) | METHOD FOR ENZYMATIC SYNTHESIS OF BETA-LACTAM ANTIBIOTICS IN THE PRESENCE OF AN ENZYME INHIBITOR | |
| RU96103686A (en) | Method of enzymatic synthesis of β-lactam antibiotics in the presence of an enzyme inhibitor | |
| JPS56161393A (en) | Beta-lactam compound | |
| GB1425571A (en) | Penicillins and cephaosporins | |
| Narisada et al. | Synthesis and substituent effects on antibacterial activity, alkaline hydrolysis rates, and infrared absorption frequencies of some cephem analogs related to latamoxef (moxalactam) | |
| DE69903719D1 (en) | METHOD FOR THE FERMENTATIVE PRODUCTION OF CEPHALOSPORINE | |
| RU2005129993A (en) | METHOD FOR PRODUCING ENANTIOMERIC FORMS OF 1,3-CYCLOHEXANDIOL DERIVATIVES IN CIS-CONFIGURATION | |
| RU96103835A (en) | IMPROVED ENZYMATIC METHOD FOR OBTAINING PENICILLINS AND CEFALOSPORINS | |
| ATE144794T1 (en) | METHOD FOR THE ENZYMATIC PRODUCTION OF 7-AMINO-CEPHALOSPORANIC ACID | |
| ITMI950383A1 (en) | IMPROVED ENZYMATIC PROCESS FOR THE PRODUCTION OF PENICILLINS AND CEPHALOSPORINS | |
| ES479732A1 (en) | Process for the preparation of semisynthetic beta-lactam antibiotics. | |
| GB1382255A (en) | Method for the production of aminopenicillins | |
| NZ331180A (en) | Specific immunophilin ligands with indole structure as antiasthmatics and immunosuppressants | |
| GB1442435A (en) | Organic compounds | |
| ATE66961T1 (en) | METHODS OF PRODUCTION OF PENEMES. | |
| ATE98248T1 (en) | PROCESS FOR THE PRODUCTION OF CEPHALOSPORIN DERIVATIVES. | |
| IL41027A (en) | The preparation of semi-synthetic penicillins and cephalosporins and novel mixed phosphonic anhydrides used as intermediates therein | |
| GB8519264D0 (en) | Chemical compounds | |
| ATE295897T1 (en) | USE OF ORTHOESTERS FOR SYNTHESIS OF CHIRAL ACIDS IN BIOCATALYTIC IRREVERSIBLE ESTERIFICATION PROCESSES | |
| RU99101111A (en) | Method of producing β-lactam antibiotics | |
| MXPA02005084A (en) | Method for producing thienopyrimidines. | |
| DK0519140T3 (en) | Process for the preparation of substituted 1,4-dihydro-4-oxo-cinnoline-3-carboxylic acids, esters and salts thereof, and between | |
| ITMI960033A1 (en) | PROCEDURE FOR THE ENZYMATIC SYNTHESIS OF B-LACTAM ANTIBIOTICS IN THE PRESENCE OF AN ENZYME INHIBITOR | |
| KR910006274A (en) | 1-difluorophenyl-7-substituted piperazinyl-3-quinolinecarboxylic acid derivatives and pharmaceutically acceptable salts thereof and methods for preparing the same |