GB1220591A - Beta-phenylalanine derivatives - Google Patents

Beta-phenylalanine derivatives

Info

Publication number
GB1220591A
GB1220591A GB24754/67A GB2475467A GB1220591A GB 1220591 A GB1220591 A GB 1220591A GB 24754/67 A GB24754/67 A GB 24754/67A GB 2475467 A GB2475467 A GB 2475467A GB 1220591 A GB1220591 A GB 1220591A
Authority
GB
United Kingdom
Prior art keywords
methoxy
hydroxy
general formula
acid
ethoxy
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.)
Expired
Application number
GB24754/67A
Inventor
Pierre Crooij
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
RIT RECH IND THERAPEUT
Original Assignee
RIT RECH IND THERAPEUT
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by RIT RECH IND THERAPEUT filed Critical RIT RECH IND THERAPEUT
Priority to GB24754/67A priority Critical patent/GB1220591A/en
Priority to DE19681768466 priority patent/DE1768466A1/en
Priority to ES354058A priority patent/ES354058A1/en
Priority to AT499368A priority patent/AT286968B/en
Priority to CH95170A priority patent/CH517700A/en
Priority to BE715588D priority patent/BE715588A/xx
Priority to CH769568A priority patent/CH515888A/en
Priority to NO204168A priority patent/NO121788B/no
Priority to NL6807465A priority patent/NL6807465A/xx
Priority to FR153043A priority patent/FR7889M/fr
Priority to FR1592518D priority patent/FR1592518A/fr
Publication of GB1220591A publication Critical patent/GB1220591A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
    • C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
    • C07C47/575—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/36—One oxygen atom
    • C07D263/42—One oxygen atom attached in position 5
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C12P41/002—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by oxidation/reduction reactions

Abstract

1,220,591. #-Phenylalanine derivatives. RECHERCHE ET INDUSTRIE THERAPEUTIQUES R.I.T. 2 May, 1968 [26 May, 1967], No. 24754/67. Heading C2C. Novel DL-, D- and L-#-phenylalanine derivatives of the general formula wherein R 1 and R 2 are each a methyl or ethyl group or one of R 1 and R 2 is a hydrogen atom or a C 2-30 acyl group and the other is a methyl or ethyl group; R 3 is a hydrogen atom, a pharmaceutically acceptable non-toxic alkali metal, ammonium, a pharmaceutically acceptable non-toxic protonated amine with which the rest of the molecule forms an acid addition salt, or a C 1-30 alkyl or C 2-30 alkenyl radical; X is a chlorine, bromine, iodine or fluorine atom; and Z is a hydrogen atom or a C 2-30 carboxylic acyl radical; and non-toxic acid addition salts thereof are prepared (a) when R 3 and Z are each a hydrogen atom, by hydrolysis and decarboxylation of a 2-benzyl-2- amino-malonic acid ester derivative of the general formula wherein Alk<SP>1</SP> is a C 1-4 alkyl radical and Y is a formyl, acetyl, benzoyl, phthaloyl or benzyloxycarbonyl radical, the reaction being conducted in a solvent under the influence of heat in an acid medium and in the presence of a reducing agent; or (b) when R 3 and Z are each a hydrogen atom, by reduction of a phenyl-pyruvic acid derivative of the general formula wherein M is as R 3 above with the exception of an alkyl or alkenyl radical, under mild conditions in the presence of ammonium hydroxide solution, followed optionally by conversion of the product to a non-toxic acid addition salt thereof or resolution of the racemic product into its D- and L-enantiomers. The L(-)ephedrine salt of (-)3-methoxy-4- hydroxy - 5 - bromo - N - acetyl - phenylalanine is prepared by adding DL-3-methoxy-4-hydroxy-5-bronio-N-acetyl-phenylalanine to an ethanolic solution of L(-)ephedrine diluted with acetone. 2 - Benzyl - 2 - aminomalonic acid ester derivatives of the second general formula above wherein R 1 is a methyl or ethyl group and R 2 is a hydrogen atom are prepared by halogenation of 3-(methoxy or ethoxy)-4-hydroxybenzaldehyde, reduction of the resulting 3-(methoxy or ethoxy) - 4 - hydroxy - 5 - halobenzaldehyde with sodium borohydride, reaction of the 3-(methoxy or ethoxy) - 4 - hydroxy - 5 - halobenzyl alcohol so obtained with a hydrogen halide and reaction of the resulting 3-(methoxy or ethoxy)-4- hydroxy-5-halobenzyl halide with an alkali metal salt of a 2-aminomalonic acid ester derivative of the general formula wherein M<SP>+</SP> is an alkali metal ion. Phenylpyruvic acid derivatives of the third general formula above are prepared by reaction of a 3-(methoxy or ethoxy)-4-hydroxy-5-halobenzaldehyde with N-acetylglycine in the presence of excess acetic anhydride and sodium acetate, mild alkaline hydrolysis of the resulting azlactone of the general formula and acid or alkaline hydrolysis of the resulting 2 - acetamido - 3 - [3<SP>1</SP>- methoxy or ethoxy)- 4<SP>1</SP> - hydroxy - 5<SP>1</SP>- halo] - phenylpropenoic acid. 5 - Bromo - isovanallin is prepared by treatment of 5-bromovanallin with anhydrous aluminium chloride in pyridine, while heating, and reaction of the resulting 5-bromo-protocatechualdehyde with methyl iodide and sodium bicarbonate in acetone. Acetamido - 3,4 - dihydroxy - 5 - chlorobenzylmalonic acid diethyl ester is prepared by treatment of diethyl acetamido-(3-methoxy-4-hydroxy - 5 - chlorobenzyl) - malonate with aluminium chloride in pyridine. Pharmaceutical compositions having hypotensive activity comprise, as active ingredient, a DL-, D- or L-#-phenylalanine derivative of the first general formula above or a non-toxic acid addition salt thereof, together with a pharmaceutically acceptable diluent or carrier, and may be administered orally, intramuscularly, intravenously or subcutaneously.
GB24754/67A 1967-05-26 1967-05-26 Beta-phenylalanine derivatives Expired GB1220591A (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
GB24754/67A GB1220591A (en) 1967-05-26 1967-05-26 Beta-phenylalanine derivatives
DE19681768466 DE1768466A1 (en) 1967-05-26 1968-05-16 New ss-phenylalanine derivatives
ES354058A ES354058A1 (en) 1967-05-26 1968-05-18 Beta-phenylalanine derivatives
AT499368A AT286968B (en) 1967-05-26 1968-05-24 Process for the preparation of new DL-, D- and L-β-phenylalanine derivatives
CH95170A CH517700A (en) 1967-05-26 1968-05-24 (A) Cpds. (I) R' and R2 = Me or Et or one only of R' or R2 may = H or (1-30C)acyl R3 = H, non-toxic cation chosen from the alkali metals and opt. su
BE715588D BE715588A (en) 1967-05-26 1968-05-24
CH769568A CH515888A (en) 1967-05-26 1968-05-24 Process for the preparation of beta-phenylalanine derivatives
NO204168A NO121788B (en) 1967-05-26 1968-05-24
NL6807465A NL6807465A (en) 1967-05-26 1968-05-27
FR153043A FR7889M (en) 1967-05-26 1968-05-27
FR1592518D FR1592518A (en) 1967-05-26 1968-05-27

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB24754/67A GB1220591A (en) 1967-05-26 1967-05-26 Beta-phenylalanine derivatives

Publications (1)

Publication Number Publication Date
GB1220591A true GB1220591A (en) 1971-01-27

Family

ID=10216725

Family Applications (1)

Application Number Title Priority Date Filing Date
GB24754/67A Expired GB1220591A (en) 1967-05-26 1967-05-26 Beta-phenylalanine derivatives

Country Status (8)

Country Link
AT (1) AT286968B (en)
BE (1) BE715588A (en)
CH (1) CH515888A (en)
DE (1) DE1768466A1 (en)
ES (1) ES354058A1 (en)
FR (2) FR1592518A (en)
GB (1) GB1220591A (en)
NL (1) NL6807465A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004110500A1 (en) * 2002-08-02 2004-12-23 Mallinckrodt Inc. Radioactively labelled amino acid analogues, their preparation and use

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE789586A (en) * 1972-03-27 1973-04-02 Hoffmann La Roche PROCESS FOR THE PREPARATION OF 3,4,5-TRIMETHOXY-BENZALDEHYDE

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004110500A1 (en) * 2002-08-02 2004-12-23 Mallinckrodt Inc. Radioactively labelled amino acid analogues, their preparation and use
US7189383B2 (en) 2002-08-02 2007-03-13 Mallinckrodt Inc. Radioactively labelled amino acid analogues, their preparation and use
AU2003304200B2 (en) * 2002-08-02 2009-10-01 Vrije Universiteit Brussel Radioactively labelled amino acid analogues, their preparation and use

Also Published As

Publication number Publication date
ES354058A1 (en) 1970-02-16
CH515888A (en) 1971-11-30
DE1768466A1 (en) 1971-09-16
BE715588A (en) 1968-10-16
FR7889M (en) 1970-05-04
NL6807465A (en) 1968-11-27
AT286968B (en) 1971-01-11
FR1592518A (en) 1970-05-19

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