NO770524L - Fremgangsm}te ved spaltning av alanin-racemater - Google Patents
Fremgangsm}te ved spaltning av alanin-racematerInfo
- Publication number
- NO770524L NO770524L NO770524A NO770524A NO770524L NO 770524 L NO770524 L NO 770524L NO 770524 A NO770524 A NO 770524A NO 770524 A NO770524 A NO 770524A NO 770524 L NO770524 L NO 770524L
- Authority
- NO
- Norway
- Prior art keywords
- alanine
- compound
- fluoroalanine
- deutero
- quinine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 11
- 235000004279 alanine Nutrition 0.000 title claims 6
- 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 title 1
- 238000000354 decomposition reaction Methods 0.000 title 1
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims description 16
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims description 9
- 235000001258 Cinchona calisaya Nutrition 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 229960000948 quinine Drugs 0.000 claims description 7
- 239000002585 base Substances 0.000 claims description 6
- UYTSRQMXRROFPU-UHFFFAOYSA-N 2-azaniumyl-3-fluoropropanoate Chemical compound FCC(N)C(O)=O UYTSRQMXRROFPU-UHFFFAOYSA-N 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 claims description 2
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 229960001404 quinidine Drugs 0.000 claims description 2
- -1 alanine compound Chemical class 0.000 claims 5
- UYTSRQMXRROFPU-MYSWAXPFSA-N (2r)-2-amino-2-deuterio-3-fluoropropanoic acid Chemical compound FC[C@@](N)([2H])C(O)=O UYTSRQMXRROFPU-MYSWAXPFSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- UYTSRQMXRROFPU-UWTATZPHSA-N (2s)-2-amino-3-fluoropropanoic acid Chemical compound FC[C@@H](N)C(O)=O UYTSRQMXRROFPU-UWTATZPHSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229960003767 alanine Drugs 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- DHALQLNIDMSKHU-REOHCLBHSA-N (2s)-2-(fluoroamino)propanoic acid Chemical compound FN[C@@H](C)C(O)=O DHALQLNIDMSKHU-REOHCLBHSA-N 0.000 description 2
- UYTSRQMXRROFPU-LIIDHCAMSA-N (2s)-2-amino-2-deuterio-3-fluoropropanoic acid Chemical compound FC[C@](N)([2H])C(O)=O UYTSRQMXRROFPU-LIIDHCAMSA-N 0.000 description 2
- UYTSRQMXRROFPU-VMNATFBRSA-N 2-amino-2-deuterio-3-fluoropropanoic acid Chemical compound FCC(N)([2H])C(O)=O UYTSRQMXRROFPU-VMNATFBRSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001294 alanine derivatives Chemical class 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229950010030 dl-alanine Drugs 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- DHALQLNIDMSKHU-UWTATZPHSA-N (2r)-2-(fluoroamino)propanoic acid Chemical compound FN[C@H](C)C(O)=O DHALQLNIDMSKHU-UWTATZPHSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/30—Preparation of optical isomers
- C07C227/34—Preparation of optical isomers by separation of optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/08—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/22—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
- C07C237/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/487—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Fire-Extinguishing Compositions (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Fremgangsmåte ved spaltning av alanin-racemater
Foreliggende oppfinnelse angår en fremgangsmåte ved spaltning av DL-alanin, 3-fluor-DL-alanindg 2-deutero-3-fluor-DL-alanin ved omsetning med en spaltende base og en (3-dicarbonylforbindelse. Der dannes azomethin-diastereomere salter som er lette å skille, og den maskerende gruppe fjernes lett under mildt sure betingelser.
Foreliggende oppfinnelse angår således fremstilling av 3~fluor-D-alanin og 2-deutero-3-fluor-D-alanin som er sterke anti-bakterielle midler som er verdifulle til å inhibere veksten av patogene bakterier av både den grampositive og gramnegative type. Mere spesielt angår oppfinnelsen fremstilling av D-alanin, 3_ f luor-D-alanin og 2 -deutero-3-f luor -D-alanin i i det vesentlige ren form ved å omsette DL-alanin, 3-fluor-DL-alanin eller 2-deutero-3-fluor-DL-alanin med en-spaltende base som kinin, kinidin, brucin, stryknin, d- eller 1-a,N,N-trimethylbenzylamin eller lignende, og en (3-dicarbonylforbindelse med formelen:
hvor R er methyl., fenyl eller alkoxy med 1-5 carbonatomer, særlig ethoxy.
Denne spaltningsprosess, skjønt den her bare anvendes på alaninforbindelser, er generelt anvendbar på alle andre a-amino-syrer.
Denne reaksjon utføres under anvendelse av omtrent ekvimolare mengder av de tre reaktanter. En lavere alkanol med 1 - 5 carbonatomer anvendes som oppløsningsmiddel, fortrinnsvis methanol. Reaksjonen finner sted under tilbakeløp av oppløsnings - midlet, og reaksjonstiden er 0,5 - 3 timer.
Reaksjonsblaridingen avkjøles så til omtrent værelsetempera-tur, og får lov til å eldes i kort tid, ca. 15 minutter til 1 time. De to diastereomere salter skilles så lett. Eksempelvis utvinnes, i tilfelle av fluoralanin og kinin, L-isomeren som et fast bunn-fall. Den faste L-isomer utvinnes ved filtrering. For å øke utbyttet kan filtratet inndampes i vakuum til en sirup og derpå spyles med et annet oppløsningsmiddel i hvilket der er en forskjell i oppløselighet mellom isomerene, for å utvinne et annet utbytte. Et passende oppløsningsmiddel i tilfelle av fluora lanin.er ethylacetat. Et volumoverskudd av oppløsningsmidlet tilsettes, og blandingen eldes i inntil 36 timer, om ønskes. Efter denne eldning kan den annen isomer lett utvinnes ved filtrering. D-isomeren utvinnes fra oppløsningsmidlet, alkanolen fra den opprinnelige reaksjon eller alkanol/ethylacetatblandingen, ved inndampning av filtratet. Den rå, faste D-isomer fåes herved.
De nye adskilte saltpar av de to diastereomere kan behandles identisk for å utvinne den optisk aktive aminosyre i ren form. Først skilles den spaltende base fra isomeren ved å blande den rå isomer med vandig alkalimetallhydroxyd, f.eks. natriumhydroxyd eller kaliumhydroxyd. Denne reaksjon finner sted praktisk talt momentant, men oppløsningen kan eldes i fra flere minutter til030 minutter. Basen felles, og kan ekstraheres under anvendelse av et oppløsningsmiddel som kloroform.
Den vandige oppløsning syres så til pH 6 eller mindre, under anvendelse av en lett tilgjengelig syre som saltsyre, eddiksyre, maursyre eller blandinger derav. Den derved erholdte klare opp-løsning ekstraheres så under anvendelse av kloroform for å fjerne (3-dicarbonylf orbindelse. Den erholdte sure oppløsning renses så ved avsaltning under anvendelse av en ionebytteharpiks i H+<->formen, og elueres så med fortynnet ammoniumhydroxyd.
De følgende eksempler illustrerer oppfinnelsen.
Eksempel 1
Til en oppløsning av 17,2 g kinin og 5,5 g 2,4-pentandion i 100 ml methanol tilsettes 5,35 g D,L-3~fluoralanin. Blandingen kokes under tilbakeløp i en inert atmosfære i 60 minutter. Den dannede oppløsning avkjøles til 20 - 22°C, eldes i 1 time, derpå frafiltreres det krystallinske kininsalt av L-N-[1-methyl-2-acetylvinyl J -a-am i no-(3-f luor-propionsyre , vaskes med kold methanol
og tørres i vakuum. Vekt: 9,9 9-
Filtratet inndampes i vakuum og behandles med 30 ml ethylacetat. Reaksjonsblandingen holdes ved ca. 0°C i flere timer, og det.f aste stoff f raf ilt reres , vaskes med ethylacetat , tørres i vakuum, og man får 3 50 g.
De faste stoffer forenes og oppløses i 20 ml vann. For å fraskille kininet tilsettes 26,5 ml IN nat riumhydroxydoppløsning langsomt under omrøring. Blandingen ekstraheres med 4 x 25 ml kloroform. Til vannfasen tilsettes 15 ml 2N eddiksyre og 19 ml IN saltsyre. Efter 10 minutter fraskilles det avspaltede 2,4-pentandion ved å ekstrahere den vandige oppløsning med kloroform.
Den sure oppløsning føres gjennom en "Dowex 50 WX 4" kolonne (H+-formen). Kolonnen vaskes med destillert vann inntil eluatet ikke lengre ér surt. L-3~fluoralaninet elueres med 0,5N ammoniumhydroxyd. Det totale eluat konsentreres under godt vakuum slik at oppløsningstemperaturen ikke overstiger 25°C. Inndampningen fortsettes inntil man får en oppslemning med volum på 10 ml eller mindre. L-.3 -f luoralanin f raf ilt reres , vaskes med en liten mengde koldt vann og tørres i vakuum.
Utbytte: 1,4 g (52,4%)
Smp.: l65-l67°C (spaltn.)
[ol] : +10,28° (c = 6 i IN HC1) .
Det forenede ethylacetatfilt rat og vaskevæsker inndampes i vakuum. Det glassaktige residuum oppløses i 20 ml vann, og D-3-fluoralaninet isoleres ved samme metode som beskrevet ovenfor.
Utbytte: 1,2 g (45%)
Smp.: l65-l67°C (spaltn.)
[a]D: -10,21° (c = 6% i IN HC1).
Eksempel 2
Til en oppløsning av 3,24 g kinin og 1,10 g 2,4-pentandion
i 30 ml methanol tilsettes 0,891.9D,L-alanin. Blandingen opp-varmes under tilbakeløp inntil en oppløsning er dannet (90 min.). Methanolen fjernes under vakuum, og det glassaktige, residuum om-krystalliseres fra 100 ml ethylacetat.
Utbyttet av kininsaltet av N-[1-methyl-2-acetylvinyl]-L-a-aminopropionsyre er 2,3 g (93%). L-alaninet frigjøres fra dette salt ved fremgangsmåten beskrevet i eksempel 1.
Utbytte av L-alanin: 382 mg (86%)
Smp-.: 297°C (spaltn.)
[a]p<2>: 8,6 (c = 6% i IN HC1).
Eksempel 3
100 g 2-deutero-3_fluor-DL-alanin behandles som beskrevet i eksempel 1.
De følgende resultater fåes: 2-deut ero-3~fluor-D-alanin:
1. høst: utbytte 57%, [a] = -10,68°
2. høst: utbytte 7,6%, [a] D= -10,30°
2-deutero-3~fluor-L-a lanin:
1. høst: utbytte 68%, [a] = +10,1°
2. høst: utbytte 1,56%, [a]D+4,87°
Claims (4)
1. Fremgangsmåte ved spaltning av en DL-blanding av en alaninforbindelse som er alanin, 3-fluoralanin eller 2-deutero-3-fluoralanin, karakterisert ved at omtrent ekvimolare mengder av alaninforbindelsen, en spaltende base som er kinin, kinidin, brucin, stryknin, d-a,N,N-trimethylbenzylamin eller 1-a ,N ,N-t rimethylbenzylamin , og en (3-dicarbonylf orbindelse med formelen:
hvor R er methyl, fenyl eller alkoxy med 1-5 carbonatomer, omsettes i en oppløsning av en lavere alkanol med 1-5 carbonatomer under tilbakeløp i 0,5 - 3 timer, og saltparet av diastereo-merene skilles ved krystallisasjon, hvorpå hver diastereomer for seg først behandles med et alkalimetallhydroxyd, derpå med H^o"1", og den respektive individuelle isomer utvinnes.
2. Fremgangsmåte ifølge krav 1,
karakterisert ved at kinin anvendes som den spaltende base.
3. Fremgangsmåte ifølge krav 1 eller 2, karakterisert ved at der anvendes en dicarbonylforbindelse hvor R er methyl.
4. Fremgangsmåte ifølge krav 1 - 3,
karakterisert ved at der som alaninforbindelse anvendes DL-3-fluoralanin.
5- Fremgangsmåte ifølge krav 1 - 3,
karakterisert ved at der som alaninforbindelse anvendes DL-2-deut ero-(3 -f luora lanin .
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/664,328 US4048224A (en) | 1976-03-05 | 1976-03-05 | Process for resolving alanine, 3-fluoro and 2-deutero-3-fluoro-DL-alanine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO770524L true NO770524L (no) | 1977-09-06 |
Family
ID=24665546
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO770524A NO770524L (no) | 1976-03-05 | 1977-02-17 | Fremgangsm}te ved spaltning av alanin-racemater |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US4048224A (no) |
| JP (1) | JPS52106814A (no) |
| AT (1) | AT348501B (no) |
| CS (1) | CS195327B2 (no) |
| DD (1) | DD129642A5 (no) |
| DK (1) | DK67477A (no) |
| ES (1) | ES456379A1 (no) |
| FI (1) | FI770493A7 (no) |
| HU (1) | HU172989B (no) |
| NL (1) | NL7701643A (no) |
| NO (1) | NO770524L (no) |
| PL (1) | PL105883B1 (no) |
| PT (1) | PT66225B (no) |
| SE (1) | SE7701710L (no) |
| SU (1) | SU786887A3 (no) |
| YU (1) | YU49477A (no) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2749203C2 (de) * | 1977-11-03 | 1981-12-17 | Riedel-De Haen Ag, 3016 Seelze | Verfahren zur Racematspaltung von DL-alpha-Aminocarbonsäuren und diastereomere Salze |
| FR2430413A1 (fr) * | 1978-07-07 | 1980-02-01 | Anvar | Procede de preparation d'alpha-aminoacides optiquement actifs, et leurs derives |
| US4264590A (en) * | 1979-05-23 | 1981-04-28 | Abbott Laboratories | Antibacterial peptide |
| US4582931A (en) * | 1984-12-24 | 1986-04-15 | Merck & Co., Inc. | Preparation of 2-Deutero-D-serine |
| KR200234713Y1 (ko) | 1998-12-31 | 2001-11-22 | 구자홍 | 전동압축기의프레임지지장치 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3028395A (en) * | 1955-03-28 | 1962-04-03 | Parke Davis & Co | Process for the resolution of optically active acids |
| US3381031A (en) * | 1962-04-18 | 1968-04-30 | Univ Australian | Resolution of racemic amino acids |
-
1976
- 1976-03-05 US US05/664,328 patent/US4048224A/en not_active Expired - Lifetime
-
1977
- 1977-02-15 FI FI770493A patent/FI770493A7/fi not_active Application Discontinuation
- 1977-02-16 DK DK67477A patent/DK67477A/da unknown
- 1977-02-16 SE SE7701710A patent/SE7701710L/xx unknown
- 1977-02-16 NL NL7701643A patent/NL7701643A/xx not_active Application Discontinuation
- 1977-02-17 NO NO770524A patent/NO770524L/no unknown
- 1977-02-21 CS CS771133A patent/CS195327B2/cs unknown
- 1977-02-22 SU SU772454448A patent/SU786887A3/ru active
- 1977-02-22 YU YU00494/77A patent/YU49477A/xx unknown
- 1977-02-23 PT PT66225A patent/PT66225B/pt unknown
- 1977-02-28 ES ES456379A patent/ES456379A1/es not_active Expired
- 1977-03-02 AT AT138277A patent/AT348501B/de not_active IP Right Cessation
- 1977-03-02 DD DD7700197629A patent/DD129642A5/xx unknown
- 1977-03-03 PL PL1977196414A patent/PL105883B1/pl unknown
- 1977-03-03 JP JP2228177A patent/JPS52106814A/ja active Pending
- 1977-03-04 HU HU77ME00002047A patent/HU172989B/hu unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AT348501B (de) | 1979-02-26 |
| SU786887A3 (ru) | 1980-12-07 |
| SE7701710L (sv) | 1977-09-06 |
| JPS52106814A (en) | 1977-09-07 |
| HU172989B (hu) | 1979-01-28 |
| DD129642A5 (de) | 1978-02-01 |
| CS195327B2 (en) | 1980-01-31 |
| DK67477A (da) | 1977-09-06 |
| NL7701643A (nl) | 1977-09-07 |
| PT66225A (en) | 1977-03-01 |
| PT66225B (en) | 1979-01-17 |
| ATA138277A (de) | 1978-07-15 |
| ES456379A1 (es) | 1978-04-16 |
| PL105883B1 (pl) | 1979-11-30 |
| FI770493A7 (no) | 1977-09-06 |
| YU49477A (en) | 1982-06-30 |
| US4048224A (en) | 1977-09-13 |
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