DE2512608A1 - D-Penicillamine prodn from benzylpenilloic acid - by reaction with phenylhydrazine in a non-aq soln - Google Patents
D-Penicillamine prodn from benzylpenilloic acid - by reaction with phenylhydrazine in a non-aq solnInfo
- Publication number
- DE2512608A1 DE2512608A1 DE19752512608 DE2512608A DE2512608A1 DE 2512608 A1 DE2512608 A1 DE 2512608A1 DE 19752512608 DE19752512608 DE 19752512608 DE 2512608 A DE2512608 A DE 2512608A DE 2512608 A1 DE2512608 A1 DE 2512608A1
- Authority
- DE
- Germany
- Prior art keywords
- penicillamine
- reaction
- phenylhydrazine
- ethanol
- acid
- 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.)
- Granted
Links
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 title claims abstract description 19
- 229960001639 penicillamine Drugs 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 title claims abstract description 9
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 title claims abstract description 8
- 229940067157 phenylhydrazine Drugs 0.000 title claims abstract description 8
- LRWFMQCGNBOTQP-OLZOCXBDSA-N benzylpenilloic acid Chemical compound N1[C@@H](C(O)=O)C(C)(C)S[C@@H]1CNC(=O)CC1=CC=CC=C1 LRWFMQCGNBOTQP-OLZOCXBDSA-N 0.000 title abstract 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 21
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 239000008096 xylene Substances 0.000 claims abstract description 5
- 239000013078 crystal Substances 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 239000002798 polar solvent Substances 0.000 claims abstract 2
- 238000003756 stirring Methods 0.000 claims abstract 2
- PSPRNQOVLYLHSA-RWMBFGLXSA-N (3S,7R,7aR)-5-benzyl-2,2-dimethyl-7,7a-dihydro-3H-imidazo[5,1-b][1,3]thiazole-3,7-dicarboxylic acid Chemical compound CC1(C)S[C@@H]2[C@H](N=C(Cc3ccccc3)N2[C@H]1C(O)=O)C(O)=O PSPRNQOVLYLHSA-RWMBFGLXSA-N 0.000 claims description 6
- 238000002955 isolation Methods 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 238000005406 washing Methods 0.000 abstract 1
- 230000015556 catabolic process Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000012736 aqueous medium Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- VXIXUWQIVKSKSA-UHFFFAOYSA-N 4-hydroxycoumarin Chemical compound C1=CC=CC2=C1OC(=O)C=C2O VXIXUWQIVKSKSA-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- ZBDOVHVJWVWSPQ-UHFFFAOYSA-N benzylpenilloaldehyde Chemical compound O=CCNC(=O)CC1=CC=CC=C1 ZBDOVHVJWVWSPQ-UHFFFAOYSA-N 0.000 description 3
- BADXJIPKFRBFOT-UHFFFAOYSA-N dimedone Chemical compound CC1(C)CC(=O)CC(=O)C1 BADXJIPKFRBFOT-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 125000001984 thiazolidinyl group Chemical group 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 238000005065 mining Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000002960 penicillins Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- OZOLRGZAVBQRBG-UHFFFAOYSA-N (2-methyl-3-nitrophenyl)boronic acid Chemical compound CC1=C(B(O)O)C=CC=C1[N+]([O-])=O OZOLRGZAVBQRBG-UHFFFAOYSA-N 0.000 description 1
- ILJCRVOHKUEEIW-UHFFFAOYSA-N 2,2,5,5-tetramethyl-1,3-thiazolidin-3-ium-4-carboxylate Chemical compound CC1(C)NC(C(O)=O)C(C)(C)S1 ILJCRVOHKUEEIW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- HCYWNSXLUZRKJX-RWMBFGLXSA-N benzylpenicilloic acid Chemical compound N1[C@@H](C(O)=O)C(C)(C)S[C@@H]1[C@@H](C(O)=O)NC(=O)CC1=CC=CC=C1 HCYWNSXLUZRKJX-RWMBFGLXSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001661 cadmium Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 150000001875 compounds Chemical group 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- BQPIGGFYSBELGY-UHFFFAOYSA-N mercury(2+) Chemical compound [Hg+2] BQPIGGFYSBELGY-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000007659 semicarbazones Chemical class 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
VERFAHREN ZUR HERSTELLUNG VON D-pENICILLAMIN Priorität vom 8. 4. 1974 Jugoslawien Nr.P-973/74 Dna Verfahren betrifft die Herstellung von D-Peniclllamin durch den Abbau des Thiazolidrings der Benzylpenillsäure. PROCESS FOR THE PRODUCTION OF D-PENICILLAMIN Priority from April 8th 1974 Yugoslavia No. P-973/74 Dna process concerns the production of D-peniclllamin by the breakdown of the thiazolide ring of benzylpenillic acid.
Der Abbau wird in eineia nichtwässrigen medium mit Phenylhydrazin durchgeführt.The degradation is carried out in a non-aqueous medium with phenylhydrazine carried out.
Penicillamin kann synthetisch oder durch den Abbau von Naturprodukten, die den Thiazolindring enthalten, wie z,B, Penicilline, erholten worden. Durch das Syntheseverfahren kann das racemische Penicillamin erhalten werden, das mit optisch aktiven Verbindungen getrennt wird. Durch den Abbau des Thiazolidrings der aus Naturpenicillinen erhaltenen Verbindungen entsteht das biologisch wirksame, optisch aktive D-Penicillamin. Das Problem, das beim Abbauverfahren entsteht, ist die Komplizierheit des Abbaus des Thiazolidinrings und die Beseitigung der Abbaunebenprodukte sowie die Verarbeitung und Reinigung des Endproduktes.Penicillamine can be produced synthetically or by breaking down natural products, that contain the thiazole indigenic, such as, for example, penicillins, have been recovered. By the Synthesis method, the racemic penicillamine can be obtained with optically active connections are disconnected. By breaking down the thiazolid ring from natural penicillins The resulting compounds form the biologically active, optically active D-penicillamine. The problem that arises with the mining process is the complexity of the mining the thiazolidine ring and the elimination of the breakdown by-products as well as the processing and cleaning of the end product.
Bei den bekannten Verfahren zur Herstellung von D-Penicillamin wird von Penicillosäuren oder Penillsäuren ausgegangen, die mittels Quecksilber-II-chlorid in wässrigem Medium abgebaut werden. Das entstandene Nebenprodukt Penilloaldehyd wird aus dem Reaktionsgemisch in der Form von Hydrazon, Oxazon oder Semicarbazon entfernt. Das Salz des Quecksilber-II-penicillamin-komplexes wird mit dem gasförmigen Schwefelwasserstoff behandelt, Nach der Entfernung des Quecksilber-(II)-sulfid-niederschlags und der Eindampfung der wässrigen Lösung im Stickstoffstrom wird das rohe D-Penicillamin in Form von Hydrochlorid erhalton. Dieses wird über die 2,2,5,5-Tetramethyl-thiazolidin-4-carbonsäure gereinigt und schliesslich mit Triäthylamin in die D-Penicillamin-base übergeführt (brit. Pat. 959 817, breit. Pat. 854 339, US-Pati. 3 281 461).In the known process for the production of D-penicillamine is from penicilloic acids or penillic acids assumed that by means of mercury-II-chloride be degraded in an aqueous medium. The resulting by-product penilloaldehyde becomes from the reaction mixture in the form of hydrazone, oxazone or semicarbazone removed. The salt of the mercury II penicillamin complex is mixed with the gaseous Treated hydrogen sulfide, after removal of the mercury (II) sulfide precipitate and evaporation of the aqueous solution in a stream of nitrogen produces the crude D-penicillamine obtained in the form of hydrochloride. This is via the 2,2,5,5-tetramethyl-thiazolidine-4-carboxylic acid cleaned and finally converted into the D-penicillamine base with triethylamine (brit. Pat. 959 817, broad. 854,339, U.S. Pat. 3,281,461).
Anstatt von Qtiecksilber-TI-chlorid können zum Abbau und Komplexformung Blei- oder Cadmiumsalze verwendet werden (DDR-Pat. 80 921).Instead of Qtiecksilber-TI-chloride you can break down and form complexes Lead or cadmium salts are used (GDR Pat. 80 921).
Es ist auch belznnt, das der Abbau des Thiazolidinringes von Benzylpenicillosäure oder Benzylpenillsäure in Wasser in Anwesenheit von 4-Hydroxy-kumarin (tschechoslow. Pat.It is also gilded that the breakdown of the thiazolidine ring of benzylpenicilloic acid or benzylpenillic acid in water in the presence of 4-hydroxycoumarin (Czechoslovak. Patient
127 553) oder von 5,5-Dimethyl-1,2-cyclodion (Dimedon) (DDR-Pat. 82 718) verläuft. Durch die Reaktion entstandene Penilloaldehyd wird im ersten Fall als 3,3'-Penillidon-bis-(4-hydroxy)-kumarin und im zweiten Fall als Penilloaldomedon entfernt. Durch die Eindampfung von Wasser unter vermindertem Druck im Stickstoffstrom bleibt als Rückstand das rohe D-Penicillamin in der Form von Hydroxychlorid oder der freien Base zurück. Durch die Erhitzung des derweise erhaltenen Produkts im abs. Äthanol wird das reine D-Penicillamin erhalten.127 553) or of 5,5-dimethyl-1,2-cyclodione (Dimedon) (DDR-Pat. 82 718) runs. Penilloaldehyde produced by the reaction is in the first case as 3,3'-penillidone-bis- (4-hydroxy) -coumarin and in the second case as penilloaldomedon removed. By evaporation of water under reduced pressure in a stream of nitrogen remains as residue the crude D-penicillamine in the form of hydroxychloride or the free base back. By heating the product thus obtained in the Section. Ethanol, the pure D-penicillamine is obtained.
Die Mängel der beschriebenen Verfahren sind die Verwendung von sehr toxischen oder teuren Rohstoffen (Quecksilber-II-chlorid, Schwefelwasserstoff, 4-Hydroxy-kumarine oder Dimedon). Die Ausbeuten liegen zwischen 19 und 80 5b. Bei allen Verfahren wird die Reaktion in wässrigem Medium, worin das Produkt löslich ist, durchgeführt. Deswegen soll Wasser durch die Eindampfung im Inertgasstrom oder durch die Lyophilisation vollständig entfernt werden. Es wird ein unreines Produkt erhalten. Die weitere Reinigung und Isolierung von D-Penicillamin ist in meisten Fällen ein aufwendiges, teures und langwieriges Prozess. Etwas einfacher ist das Verfahren mit Dimedon, in diesem Falle werden jedoch niedrige Ausbeuten (etwa 50 % d. Theor.) erhalten.The shortcomings of the procedures described are the use of very much toxic or expensive raw materials (mercury-II-chloride, hydrogen sulfide, 4-hydroxy-coumarins or Dimedon). The yields are between 19 and 80 5b. In all procedures will the reaction is carried out in an aqueous medium in which the product is soluble. Because of this should water by evaporation in an inert gas stream or by lyophilization be completely removed. An impure product is obtained. The other Purification and isolation of D-penicillamine is in most cases a laborious, expensive and tedious process. The process with Dimedon is a little easier, in this case, however, low yields (about 50% of theory) are obtained.
Wir haben gefunden, dass die Reaktion des Abbaus von Thiazolidinring der Benzylpenillsäure vorteilhafter mittels Phenylhydrazin in nichtwässrigem Medium verläuft. Als Lösungsmittel können niedrigere Alkohole, Benzen, Toluen oder Xylen verwendet werden. iNach diesem Verfahren kommt es nicht zur Bildung von Penilloaldehyd, sondern zum direkten Angriff von Phenylhydrazin auf den Thiazolidring der Benzylpenillsäure. Das durch die Reaktion enstandene Hydrazon ist in heissem auserwähltem Lösungsmittel löslich, während D-Penicillamin im Laufe der Reaktion kristallisiert.We found that the reaction is the breakdown of thiazolidine ring of benzylpenilic acid more advantageously by means of phenylhydrazine in a non-aqueous medium runs. Lower alcohols, benzene, toluene or xylene can be used as solvents be used. iAfter this procedure comes it's not for education from penilloaldehyde, but rather to the direct attack of phenylhydrazine on the thiazolide ring of benzylpenillic acid. The hydrazone produced by the reaction is hot Soluble in selected solvent, while D-penicillamine in the course of the reaction crystallized.
Erfindungsgemäss wird derart verfahren, dass ein Gemisch von Benzylpenillsäure und Phenylhydrazin in abs. Äthanol, Benzen, 'l'oluen oder Xylen 2 Stunden auf eine Temperatur von 70 bis von D-Penicillamin 140°C erhitzt wird. Die erhalten Kristalle/werden aus dem heissen Gemisch abgesaugt und mit heissem abs. Äthanol gewaschen.According to the invention, the procedure is such that a mixture of benzylpenillic acid and phenylhydrazine in abs. Ethanol, benzene, l'oluene or xylene for 2 hours at a time Temperature from 70 to 140 ° C of D-penicillamine is heated. The received crystals / become sucked out of the hot mixture and with hot abs. Washed ethanol.
Der Vorteil dieser Erfindung ist ein einfaches, schnelles und leicht durchführbares Ver£ahron. Nach einfachem Isolationsprozess wird das reine Produkt erhalten. Bs werden keine teuren und toxischen Rohstoffe verwendet. Weder im laufe der reaktion noch bei der Isolation braucht man in Inertgasstrom zu arbeiten. Es werden die besten Ausbeuten erhalten.The advantage of this invention is simple, quick and easy practicable ordinance. After a simple isolation process, the pure product becomes obtain. No expensive and toxic raw materials are used. Neither in the run the reaction during the insulation process requires working in a stream of inert gas. It the best yields are obtained.
Das Verfahren wird durch folgende Beispiele erläutert.The following examples illustrate the process.
Beispiel 1 Bin Gemisch aus 20 g (0,065 Mol) Benzylpenillsäure, 21 g-(0,194 Mol) Phenylhydrazin und 60 ml abs. Äthanol wird 2 Stunden gerührt und auf Siedetemperatur gehalten. :Das heisse Reaktionsgemisch wird filtriert. Auf dem Filter zurückgelassene Kristalle von D-Penicillamin werden mit 30 ml heitm abs. Äthanol gewaschen. Es werden 7,5 g D-Penicillamin (77,5 %) erhalten. Der Gehalt ist 98,5 %, [α]D25 = -60,7°.Example 1 A mixture of 20 g (0.065 mol) of benzylpenillic acid, 21 g- (0.194 mol) phenylhydrazine and 60 ml abs. Ethanol is stirred for 2 hours and on Maintained boiling temperature. : The hot reaction mixture is filtered. On the filter Crystals of D-penicillamine left behind are mixed with 30 ml of abs. Ethanol washed. 7.5 g of D-penicillamine (77.5%) are obtained. The salary is 98.5 %, [α] D25 = -60.7 °.
Beispiel 2 Es wird analog dem im Beispiel 1 beschriebenen 'Verfahren gearbeitet, wobei anstatt abs. Äthanols 100 ml Benzen verwendet werden. Es werden 8,9 g D-Penicillamin (92 %) erhalten. Der Gehalt ist 98,7 %, [α]D25 = - 61,3°.Example 2 The procedure described in Example 1 is repeated worked, instead of abs. Ethanol 100 ml of benzene can be used. It will 8.9 g of D-penicillamine (92%) were obtained. The content is 98.7%, [α] D25 = - 61.3 °.
Beispiel 3 Es wird analog dem im Beispiel 1 beschriebenen Verfahren gearbeitet, wobei anstatt abs. Ethanols 100 ml Toluen verwendet werden. Es werden 9,0 g D-Penicillamin (93 %) erhalten. Der Gehalt ist 99 %, [α]D25 = -60,9°.Example 3 The procedure described in Example 1 is repeated worked, instead of abs. Ethanol 100 ml of toluene can be used. It will 9.0 g of D-penicillamine (93%) were obtained. The content is 99%, [α] D25 = -60.9 °.
Beispiel 4 Es wird analog dem im Beispiel 1 beschriebenen Verfahren gearbeitet, wobei anstatt abs. Xthanols 100 ml Xylen verwendet worden. Es werden 8,9 g D-Penicllamin (92 %) erhalten. Der Gehalt ist 98,6 %, [α]D25 = -60,5°.Example 4 The procedure described in Example 1 is repeated worked, instead of abs. Xthanols 100 ml of xylene have been used. It will 8.9 g of D-penicllamine (92%) were obtained. The content is 98.6%, [α] D25 = -60.5 °.
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU97374A YU97374A (en) | 1974-04-08 | 1974-04-08 | Process for preparing d-penicillamine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2512608A1 true DE2512608A1 (en) | 1975-10-23 |
| DE2512608C2 DE2512608C2 (en) | 1982-10-21 |
Family
ID=25552228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19752512608 Expired DE2512608C2 (en) | 1974-04-08 | 1975-03-21 | Process for the preparation of D-penicillamine |
Country Status (5)
| Country | Link |
|---|---|
| AT (1) | AT337150B (en) |
| CH (1) | CH598210A5 (en) |
| DE (1) | DE2512608C2 (en) |
| SU (1) | SU557753A3 (en) |
| YU (1) | YU97374A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2728870A1 (en) * | 1976-07-10 | 1978-01-12 | Taisho Pharma Co Ltd | PROCESS FOR THE PREPARATION OF D-PENICILLAMINE AND ITS SALT |
| CN102627592A (en) * | 2012-03-16 | 2012-08-08 | 石家庄学院 | Preparation method of high-purity D-penicillamine |
-
1974
- 1974-04-08 YU YU97374A patent/YU97374A/en unknown
-
1975
- 1975-03-19 CH CH351675A patent/CH598210A5/xx not_active IP Right Cessation
- 1975-03-21 DE DE19752512608 patent/DE2512608C2/en not_active Expired
- 1975-03-27 AT AT234875A patent/AT337150B/en not_active IP Right Cessation
- 1975-04-07 SU SU2121914A patent/SU557753A3/en active
Non-Patent Citations (1)
| Title |
|---|
| NICHTS-ERMITTELT * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2728870A1 (en) * | 1976-07-10 | 1978-01-12 | Taisho Pharma Co Ltd | PROCESS FOR THE PREPARATION OF D-PENICILLAMINE AND ITS SALT |
| CN102627592A (en) * | 2012-03-16 | 2012-08-08 | 石家庄学院 | Preparation method of high-purity D-penicillamine |
Also Published As
| Publication number | Publication date |
|---|---|
| ATA234875A (en) | 1976-10-15 |
| SU557753A3 (en) | 1977-05-05 |
| AT337150B (en) | 1977-06-10 |
| CH598210A5 (en) | 1978-04-28 |
| YU97374A (en) | 1980-04-30 |
| DE2512608C2 (en) | 1982-10-21 |
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