DE2454841A1 - Verfahren zur herstellung von d(-) -alpha-amino-p-hydroxybenzylpenicillin - Google Patents
Verfahren zur herstellung von d(-) -alpha-amino-p-hydroxybenzylpenicillinInfo
- Publication number
- DE2454841A1 DE2454841A1 DE19742454841 DE2454841A DE2454841A1 DE 2454841 A1 DE2454841 A1 DE 2454841A1 DE 19742454841 DE19742454841 DE 19742454841 DE 2454841 A DE2454841 A DE 2454841A DE 2454841 A1 DE2454841 A1 DE 2454841A1
- Authority
- DE
- Germany
- Prior art keywords
- amino
- penicillin
- acid
- imino
- alpha
- Prior art date
- 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.)
- Pending
Links
- 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 title claims abstract description 26
- 229930182555 Penicillin Natural products 0.000 title claims abstract description 15
- 229940056360 penicillin g Drugs 0.000 title claims abstract description 12
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 title claims abstract description 7
- 229940049954 penicillin Drugs 0.000 title claims abstract 4
- 238000005917 acylation reaction Methods 0.000 title 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 34
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 150000002960 penicillins Chemical class 0.000 claims abstract description 11
- 235000010633 broth Nutrition 0.000 claims abstract description 10
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000008064 anhydrides Chemical class 0.000 claims abstract description 8
- 235000019371 penicillin G benzathine Nutrition 0.000 claims abstract description 7
- 239000012320 chlorinating reagent Substances 0.000 claims abstract description 5
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 229930195708 Penicillin V Natural products 0.000 claims abstract description 4
- JSYGRUBHOCKMGQ-UHFFFAOYSA-N dichloramine Chemical compound ClNCl JSYGRUBHOCKMGQ-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 4
- 239000011707 mineral Substances 0.000 claims abstract description 4
- 229940056367 penicillin v Drugs 0.000 claims abstract description 4
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 claims abstract description 4
- 239000002253 acid Substances 0.000 claims abstract description 3
- 150000002148 esters Chemical class 0.000 claims abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 12
- -1 ethoxyvinyl Chemical group 0.000 claims description 11
- 238000000855 fermentation Methods 0.000 claims description 10
- 230000004151 fermentation Effects 0.000 claims description 10
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 150000003138 primary alcohols Chemical class 0.000 claims description 2
- GGGUKEUZOYLABH-UHFFFAOYSA-N 2-[(4-ethoxy-4-oxobut-2-en-2-yl)amino]-2-(4-hydroxyphenyl)acetic acid Chemical compound CCOC(=O)C=C(C)NC(C(O)=O)C1=CC=C(O)C=C1 GGGUKEUZOYLABH-UHFFFAOYSA-N 0.000 claims 1
- 229960003022 amoxicillin Drugs 0.000 abstract description 9
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 abstract description 9
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 abstract description 8
- 230000002906 microbiologic effect Effects 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 1
- 230000020176 deacylation Effects 0.000 abstract 1
- 238000005947 deacylation reaction Methods 0.000 abstract 1
- 239000000284 extract Substances 0.000 abstract 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 238000005580 one pot reaction Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 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 description 7
- 239000008346 aqueous phase Substances 0.000 description 4
- LIKFHECYJZWXFJ-UHFFFAOYSA-N dimethyldichlorosilane Chemical compound C[Si](C)(Cl)Cl LIKFHECYJZWXFJ-UHFFFAOYSA-N 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- LJCWONGJFPCTTL-UHFFFAOYSA-N 4-hydroxyphenylglycine Chemical class OC(=O)C(N)C1=CC=C(O)C=C1 LJCWONGJFPCTTL-UHFFFAOYSA-N 0.000 description 2
- 241000209149 Zea Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- WPWHSFAFEBZWBB-UHFFFAOYSA-N 1-butyl radical Chemical compound [CH2]CCC WPWHSFAFEBZWBB-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2287774 | 1974-05-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2454841A1 true DE2454841A1 (de) | 1975-11-27 |
Family
ID=11201449
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19742454841 Pending DE2454841A1 (de) | 1974-05-17 | 1974-11-19 | Verfahren zur herstellung von d(-) -alpha-amino-p-hydroxybenzylpenicillin |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS50149695A (ref) |
| AT (1) | AT335063B (ref) |
| DE (1) | DE2454841A1 (ref) |
| ES (1) | ES432058A1 (ref) |
| FI (1) | FI340874A7 (ref) |
| NL (1) | NL7414083A (ref) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0001133A1 (en) * | 1977-09-06 | 1979-03-21 | Gist-Brocades N.V. | Process for the preparation of 6- D-alpha-amino-(p-hydroxyphenyl)-acetamido penicillanic acid |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1258275A3 (en) * | 1996-12-06 | 2003-02-26 | Advanced Phytonics Limited | Materials treatment apparatus |
-
1974
- 1974-10-28 NL NL7414083A patent/NL7414083A/xx unknown
- 1974-11-12 ES ES432058A patent/ES432058A1/es not_active Expired
- 1974-11-19 DE DE19742454841 patent/DE2454841A1/de active Pending
- 1974-11-26 FI FI3408/74A patent/FI340874A7/fi unknown
- 1974-12-16 AT AT1002874A patent/AT335063B/de not_active IP Right Cessation
- 1974-12-28 JP JP49149289A patent/JPS50149695A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0001133A1 (en) * | 1977-09-06 | 1979-03-21 | Gist-Brocades N.V. | Process for the preparation of 6- D-alpha-amino-(p-hydroxyphenyl)-acetamido penicillanic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| FI340874A7 (ref) | 1975-11-18 |
| ATA1002874A (de) | 1976-06-15 |
| JPS50149695A (ref) | 1975-11-29 |
| AT335063B (de) | 1977-02-25 |
| NL7414083A (nl) | 1975-11-19 |
| ES432058A1 (es) | 1976-11-01 |
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