CH449646A - Process for the production of new amino acids - Google Patents
Process for the production of new amino acidsInfo
- Publication number
- CH449646A CH449646A CH655267A CH655267A CH449646A CH 449646 A CH449646 A CH 449646A CH 655267 A CH655267 A CH 655267A CH 655267 A CH655267 A CH 655267A CH 449646 A CH449646 A CH 449646A
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- compound
- salts
- group
- amino acids
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 14
- 150000001413 amino acids Chemical class 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 6
- -1 Hydrogen halides Chemical class 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 description 1
- FZKCAHQKNJXICB-UHFFFAOYSA-N 2,1-benzoxazole Chemical compound C1=CC=CC2=CON=C21 FZKCAHQKNJXICB-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 244000248349 Citrus limon Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/86—Oxygen atoms
- C07D211/88—Oxygen atoms attached in positions 2 and 6, e.g. glutarimide
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung neuer Aminosäuren
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von Aminosäuren der allgemeinen Formel
EMI1.1
worin R ein Halogenatom, z. B. ein Fluor-, Chloroder Bromatom, oder das Pseudohalogen Trifluormethyl bedeutet, und ihrer Salze.
Die neuen Verbindungen besitzen wertvolle pbar- makologische, insbesondere zentralhemmende Ei den schaften. So hemmen sie beispielsweise bei Versuchen an Mäusen, Katzen, Kaninchen und Hunden die Aktivität von Neuren, die an der Steuerung der Motorik beteiligt sind. Sie können dementsprechend als zentralhemmende Mittel verwendet werden. Die neuen Verbindungen sind aber auch als Zwischenprodukte, z. B. zur Herstellung von Heilmitteln, wertvoll.
Besonders hervorzuheben ist die ss-Amino-P(p- chlorphenyl)-butbersäure.
Das erfindungsgemässe Verfahren zur Herstellung der neuen Verbindungen ist dadurch gekennzeichnet, dass man eine Verbindung der Formel
EMI1.2
worin R die e angegebene Bedeutung hat und X einen durch Hydrolyse in die Carboxylgruppe überführbaren Rest bedeutet, hydrolysiert.
Ein durch Hydrolyse in die Carboxylgruppe überführbarer Rest ist z. B. eine funktionell abgewandelte Carboxylgruppe, beispielsweise eine Carbamylgruppe, Nitrilgruppe oder eine veresterte Carboxylgruppe, wie z. B. eine Carbalkoxygruppe.
Die Hydrolyse der genannten Gruppen kann in üblicher Weise erfolgen, beispielsweise in Anwesenheit von wässrigen Säuren oder Alkalien und bei normaler oder erhöhter Temperatur.
Je nach den Verfabrensbedingungen und Ausgangs stoffen erhält man die Endstoffe in freier Form oder in der Form ihrer Salze. So können beispielsweise basi sche, neutrale, saure oder gemischte Salze, gegebenen falls auch Hemi-, Mono-, Sesqui- oder Polyhydrate davon erhalten werden. Die Salze der neuen Verbin dungen können in an sich bekannter Weise in die freien Verbindungen übergeführt wenden; Säureaddi tionssalze z. B. mit basischen Mitteln, wie Alkalien oder Ionenaustauscher, Salze mit Basen durch Reak tion mit sauren Mitteln, wie Säuren. Andrerseits kön nen erhaltene freie Aminosäuren mit Basen, insbeson- dere mit therapeutisch verwendbaren Basen, z. B.
Metallbydroxyden oder basischen Salzen, speziell Alkali- oder Erdalkalimetallhydroxyden, wie Natrium-, Kalium- oder Calciumhydroxyd, Alkalimetallcarbona ten, wie Natrium- oder Kaliumcarbonat, Ammoniak oder organischen Aminen, oder mit organischen oder anorganischen Säuren, Salze bilden. Zur Herstellung von Säureadditionssalzen werden insbesondere thera peutisch verwendbare Säuren verwendet, z.
B Halogen wasserstoffsäuren, Schwefelsäure, Phosphorsäuren, Sal petersäure, Perchlorsäure; aliphatische, alicyclische, aromatische oder heterocyclische Carbon-oder Sulfon säuren, wie Ameisen-, Essig, Propion-, Bernstein-,
Glykol-, Milch-, ipfel-, Weine Zitronen-, Ascorbin-,
Malein-, Hydroxym alein- oder Brenztraubensäure;
Phenylessig-, Benwe-, p-Aminobenzoe-, Anthranil-, p-Hydroxy-benzoe-, Salicyl- oder p-Aminosalicylsäure,
Embonsäure, Methansulfon-, Athansulfon-, Hydroxy äthansulfon-, Athylensulfonsäure;
Halogenbenzolsulton-,
Toluolsulfon-, Naphthalinsulfonsäuren oder Sulfanil säure; Methionin, Tryptophan, Lysin oder Arginin.
Diese oder andere Salze der neuen Verbindungen, wie z. B. die Pikrate, können auch zur Reinigung der erhaltenen freien Verbindungen dienen, indem man die freien Verbindungen in Salze überführt, diese abtrennt und aus den Salzen wiederum die freien Verbindungen freimacht.
Die neuen Verbindungen können in Form von Racematen vorliegen, die sich in üblicher Weise in die optischen Antipoden zerlegen lassen.
Für die erfindungsgemässen Reaktionen werden vornehmlich solche Ausgangsstoffe verwendet, die die oben erwähnten bevorzugten Verbindungen ergeben.
Die Ausgangsstoffe sind bekannt oder können nach an sich bekannten Methoden gewonnen werden.
Die neuen Verbindungen können als Heilmittel, z. B. in Form pharmazeutischer Präparate, Verwendung finden, welche sie in freier Form oder in Form ihrer Salze in Mischung mit einem für die enterale oder parenterale Applikation geeigneten pharmazeutischen organischen oder anorganischen, festen oder flüssigen Trägermaterial enthalten.
Die neuen Verbindungen können auch in der Tiermedizin, z. B. in einer der oben genannten Formen oder in Form von Futtermitteln oder von Zusatzmitteln für Tierfutter verwendet werden.
Im folgenden Beispiel sind die Temperaturen in Celsiusgraden angegeben.
Beispiel 10 g l-kmino-p- (phlorphenyl) - buttersäureäthyl- ester-hydrochlorid werden in 20 ml konzentrierter wäsr seriger Salzsäure 8 Stunden unter Rückfluss gekocht.
Anschliessend wird die Lösung im Wasserstrahlva kuum bei 40-50 zur Trockne eingedampft. Als Rückstand erhält man das kristallisierte, rohe Hydrochlorid der y-Amino-lJ-(p-chlorphenyl)-buttersäure. Zur Reinigung wird das Hydrochlorid inAceton suspendiert, abfiltriert und mit Aceton nachgewaschen. Man löst das gereinigte Hydrochlorid in 20 ml Wasser und stellt die Lösung durch Zusatz von 2-n. Natronlauge auf einen pH-Wert von 6-7. Dabei kristallisiert die freie y-Ami- no-ss-(p-chlorphenyl)-buttersäure aus. Zur Reinigung wird die Verbindung aus Wasser umkristallisiert, F.
206-208 .
Das als Ausgangsmaterial verwendete y-Amin*ss-( chlofphenyl)-buttersäureäthylester-hydrochlorid kann durch katalytische Reduktion von BCyano-pchlur- dihydrozimtsäureäthylester in Gegenwart von Palladium- kohle und 1 Mol Chlorwasserstoffsäure erhalten werden.
In analoger Weise kann man die y-Amino-ss-(p- bromophenyl)-buttersäure, F. 228-229 , erhalten.
Process for the production of new amino acids
The present invention relates to a process for the preparation of amino acids of the general formula
EMI1.1
wherein R is a halogen atom, e.g. B. a fluorine, chlorine or bromine atom, or the pseudohalogen trifluoromethyl, and their salts.
The new compounds have valuable pbaracological, in particular centrally inhibiting properties. In experiments on mice, cats, rabbits and dogs, for example, they inhibit the activity of neurs involved in controlling motor skills. Accordingly, they can be used as central inhibitors. The new compounds are also available as intermediates, e.g. B. for the production of medicines, valuable.
Particularly noteworthy is the ß-amino-P (p-chlorophenyl) -butberic acid.
The process according to the invention for preparing the new compounds is characterized in that a compound of the formula
EMI1.2
where R has the meaning given and X is a radical which can be converted into the carboxyl group by hydrolysis, hydrolyzed.
A radical which can be converted into the carboxyl group by hydrolysis is e.g. B. a functionally modified carboxyl group, for example a carbamyl group, nitrile group or an esterified carboxyl group, such as. B. a carbalkoxy group.
The groups mentioned can be hydrolyzed in the customary manner, for example in the presence of aqueous acids or alkalis and at normal or elevated temperature.
Depending on the process conditions and starting materials, the end products are obtained in free form or in the form of their salts. For example, basic, neutral, acidic or mixed salts, optionally also hemi-, mono-, sesqui- or polyhydrates thereof, can be obtained. The salts of the new compounds can be converted into the free compounds in a manner known per se; Acid addition salts z. B. with basic agents such as alkalis or ion exchangers, salts with bases by reac tion with acidic agents such as acids. On the other hand, NEN free amino acids obtained with bases, in particular with therapeutically usable bases, z. B.
Metal hydroxides or basic salts, especially alkali or alkaline earth metal hydroxides, such as sodium, potassium or calcium hydroxide, alkali metal carbonates such as sodium or potassium carbonate, ammonia or organic amines, or with organic or inorganic acids, form salts. For the preparation of acid addition salts, in particular therapeutically usable acids are used, for.
B Hydrogen halides, sulfuric acid, phosphoric acids, nitric acid, perchloric acid; aliphatic, alicyclic, aromatic or heterocyclic carboxylic or sulfonic acids, such as formic, vinegar, propionic, amber,
Glycol, milk, ipfel, wines lemon, ascorbic,
Maleic, hydroxymalic or pyruvic acid;
Phenylacetic, benwe, p-aminobenzoic, anthranil, p-hydroxy-benzoic, salicylic or p-aminosalicylic acid,
Emboxylic acid, methanesulfonic, ethanesulfonic, hydroxy ethanesulfonic, ethylene sulfonic acid;
Halobenzene sultone,
Toluenesulfonic, naphthalenesulfonic or sulfanilic acid; Methionine, tryptophan, lysine or arginine.
These or other salts of the new compounds, such as. B. the picrates can also be used to purify the free compounds obtained by converting the free compounds into salts, separating them and in turn frees the free compounds from the salts.
The new compounds can be in the form of racemates which can be broken down into the optical antipodes in the usual way.
For the reactions according to the invention, those starting materials are primarily used which give the preferred compounds mentioned above.
The starting materials are known or can be obtained by methods known per se.
The new compounds can be used as remedies, e.g. B. in the form of pharmaceutical preparations, which they contain in free form or in the form of their salts in a mixture with a pharmaceutical organic or inorganic, solid or liquid carrier material suitable for enteral or parenteral administration.
The new compounds can also be used in veterinary medicine, e.g. B. in one of the forms mentioned above or in the form of feed or additives for animal feed.
In the following example the temperatures are given in degrees Celsius.
Example 10 g of ethyl l-kmino-p- (phlophenyl) -butyric acid ester hydrochloride are refluxed for 8 hours in 20 ml of concentrated aqueous hydrochloric acid.
The solution is then evaporated to dryness in a water jet vacuum at 40-50. The residue obtained is the crystallized, crude hydrochloride of γ-amino-lJ- (p-chlorophenyl) butyric acid. For purification, the hydrochloride is suspended in acetone, filtered off and washed with acetone. The purified hydrochloride is dissolved in 20 ml of water and the solution is made by adding 2-n. Sodium hydroxide solution to a pH of 6-7. The free y-amino-ss- (p-chlorophenyl) butyric acid crystallizes out. For purification, the compound is recrystallized from water, F.
206-208.
The ethyl y-amine * ss- (chlorophenyl) -butyric acid hydrochloride used as starting material can be obtained by catalytic reduction of ethyl cyano-pchlorodihydrocinnamate in the presence of palladium carbon and 1 mol of hydrochloric acid.
The y-amino-ss- (p-bromophenyl) butyric acid, mp 228-229, can be obtained in an analogous manner.
Claims (1)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH655267A CH449646A (en) | 1963-07-09 | 1963-07-09 | Process for the production of new amino acids |
| NL646407755A NL141379B (en) | 1963-07-09 | 1964-07-08 | PROCEDURE FOR PREPARING AMINO ACIDS, PROCEDURE FOR PREPARING MEDICINAL PRODUCTS WITH CENTRAL INHIBITING ACTION AND FORMED PREPARATIONS OBTAINED BY APPLYING THIS PROCESS. |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH655267A CH449646A (en) | 1963-07-09 | 1963-07-09 | Process for the production of new amino acids |
| CH853763A CH446376A (en) | 1963-07-09 | 1963-07-09 | Process for the production of new amino acids |
| CH672964 | 1964-05-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH449646A true CH449646A (en) | 1968-01-15 |
Family
ID=27175525
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH655267A CH449646A (en) | 1963-07-09 | 1963-07-09 | Process for the production of new amino acids |
Country Status (2)
| Country | Link |
|---|---|
| CH (1) | CH449646A (en) |
| NL (1) | NL141379B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1182897A (en) * | 1995-12-20 | 1997-07-14 | Farmarc Nederland Bv | A process for the optical resolution of 3-(p-chlorophenyl)-glutaramide |
| GB2619970A (en) | 2022-06-24 | 2023-12-27 | Novumgen Ltd | An orodispersible pharmaceutical composition of baclofen and its process of preparation |
-
1963
- 1963-07-09 CH CH655267A patent/CH449646A/en unknown
-
1964
- 1964-07-08 NL NL646407755A patent/NL141379B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NL141379B (en) | 1974-03-15 |
| NL6407755A (en) | 1965-01-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CH449645A (en) | Process for the production of new amino acids | |
| CH449046A (en) | Process for the production of new amino acids | |
| CH622491A5 (en) | Process for the preparation of novel hydroxypropylamines | |
| CH449646A (en) | Process for the production of new amino acids | |
| DE2347015C2 (en) | New pyrazolyloxyacetic acid derivatives, processes for their preparation and compositions containing them | |
| DE2653251A1 (en) | AZABICYCLO SQUARE BRACKET ON 3.1.O SQUARE BRACKET FOR HEXANE DERIVATIVES, THEIR PRODUCTION AND USE | |
| DE1227893B (en) | Process for the preparation of glycyrrhetinic acid derivatives | |
| CH462841A (en) | Process for the production of new amino acids | |
| DE2206849C2 (en) | Process for the resolution of 2- (2β-benzyloxymethyl-3α-hydroxy-4-cyclopentene-1α-yl) -acetic acid | |
| AT354432B (en) | METHOD FOR PRODUCING 3-INDOLYLESSIC ACIDS | |
| DE1670143C3 (en) | ||
| CH620414A5 (en) | ||
| DE1246742B (en) | Process for the production of new phenothiazines | |
| DE3408850C2 (en) | ||
| DE731560C (en) | Process for the production of basic acid amides | |
| DE1900948C (en) | Cis- and trans-2-methyl-5- (3, 4, S-trimethoxybenzamidoJ-decahydroisoquinoline | |
| DE1241450B (en) | Process for the production of new acetamide derivatives with sedative effects | |
| DE1493536C (en) | New gamma-amino-beta-phenyl-butyric acids | |
| CH455806A (en) | Process for the production of new imidazoles | |
| AT273964B (en) | Process for the preparation of new benzheterocyclic compounds and their salts | |
| AT241461B (en) | Process for the preparation of substituted isonicotinic acid thioamides | |
| DE1156814B (en) | Process for the preparation of ª-morpholino-fatty acid anilides | |
| CH509309A (en) | 1-3-methyl-piperidino-methyl-isatin-3-thiosemicarbazone | |
| CH655930A5 (en) | METHOD FOR PRODUCING 3-HYDROXYBENZEDIAZEPINONES. | |
| CH359703A (en) | Process for the production of new piperidines |