GB807687A - Phenoxazone-dicarboxylic acid derivatives - Google Patents

Phenoxazone-dicarboxylic acid derivatives

Info

Publication number
GB807687A
GB807687A GB30910/56A GB3091056A GB807687A GB 807687 A GB807687 A GB 807687A GB 30910/56 A GB30910/56 A GB 30910/56A GB 3091056 A GB3091056 A GB 3091056A GB 807687 A GB807687 A GB 807687A
Authority
GB
United Kingdom
Prior art keywords
acid
ester
actinocyl
amino
bis
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
GB30910/56A
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.)
Bayer AG
Original Assignee
Bayer AG
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 Bayer AG filed Critical Bayer AG
Publication of GB807687A publication Critical patent/GB807687A/en
Expired legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D265/00Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/281,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/341,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
    • C07D265/38[b, e]-condensed with two six-membered rings

Abstract

The invention comprises compounds of the general formula <FORM:0807687/IV (b)/1> where X represents an amino or hydroxy radical; and R and R1 are identical and each represents a carboxyl or a carboalkoxy radical or a carbonyl radical linked in acid-amide fashion to an alkylamino group, an amino acid, an amino acid ester, an alkamino acid, an acetoxyamino acid, an acetoxyamino acid ester, a polypeptide, a polypeptide ester, a peptidelactone or a polypeptidelactone residue, and the preparation of those compounds of the above general formula wherein X is an amino group by subjecting a 4-methyl-3-hydroxy-2-aminobenzoic acid or an N-carbonyl substituted amino acid derivative thereof to oxidation. In the examples (in which the compound of the general formula above wherein X is -NH2 and R and R1 are -COOH is referred to as Actinocin, the corresponding -OH compound as Desamino-actinocin, and the divalent acid radicals derived therefrom as Actinocyl and Desamino-actinocyl respectively): Actinocin is prepared by dissolving 4-methyl-3-hydroxy-anthranilic acid in N/10 caustic soda (pH = 9.5) and oxidizing it with M/10 potassium ferricyanide solution, the resulting solution being at pH 3.5. Alternatively actinocin is prepared by oxidation of a solution of 4-methyl-3-hydroxyanthranilic acid in aqueous ammonium carbonate by a rapid stream of air. Methylation of actinocin by methyl iodide and silver oxide yields actinocin dimethyl ester which is also prepared by oxidation of a chloroformic solution of the methyl ester of 4-methyl-3-hydroxyanthranilic acid with yellow mercuric oxide. From the correspondingly substituted anthraacids the following compounds are prepared by oxidation in ammonium carbonate solution with air: N,N1-actinocyl-bis-aminoethanoic acid dimethyl ester, N,N1-actinocylbis - O - acetyl - threonine dimethyl ester, N,N1 - actinocyl - bis - glutathion - tetramethyl ester, N,N1 - actinocyl - bis - p - aminobenzoyl-b - alanylsarcosine diethyl ester, N,N1-actinocyl - bis - p - aminobenzoyl - glycylsarcosine diethyl ester, N,N1 - actinocyl - bis - p-aminobenzoyl - glutamic acid tetraethyl ester, N,N1 - actinocyl - bis - d - amino - g - valerolactone and N,N1 - actinocyl - bis - ethylamine. Also by oxidation with ferricyanide are prepared: N,N1-actinocyl-bis-aminoethanoic acid (also prepared from its ethyl ester by hydrolysis with sodium hydroxide solution), N,N1-actino-cyl - bis - glycylvaline, N,N1 - actinocyl - bisglycylvalylproline and N,N1-actinocyl-bis-threonine. In examples of compounds of the general formula above wherein X is OH, desamino-actinocin dimethyl ester is prepared by refluxing actinocin dimethyl ester with glacial acetic acid and water, extracting the dye with chloroform filtering the solution through a short column of silica gel and concentrating the filtrate. Similarly is prepared N,N1-(desamino-actinocyl)-bisaminoethanoic acid dimethyl ester, the dye after extraction being methylated with methyl iodide and silver oxide and adsorption on silica gel yielding two fractions, one comprising the ester and the other its 2-methyl ether; and N,N1 - (desamino - actinocyl) - bis - O - acetylthreonine and N,N1 - (desamino - actinocyl)-bis-threonine, the compounds being separated by adsorption on silica gel. 2 - Amino - 3 - hydroxy - 4 - methylbenzoic acid is prepared either by hydrolysis of its 3-methyl ether or reduction by sodium dithionite of the 2 - nitro compound; 2 - amino - 3 - hydroxy - 4-methylbenzoic acid methyl ester by treating the 2-nitro - 3 - hydroxy - 4 - methylbenzoic acid with methanolic hydrochloric acid solution to form 2-nitro - 3 - hydroxy - 4 methylbenzoic acid methyl ester and reducing this with sodium dithionite; N - (2 - amino - 3 - hydroxy - 4 - methylbenzoyl)-R (where R is an O-acetyl threonine, a glutathion, a p - amino - benzoyl - b - alanyl - sarcosine ethyl ester, a p - amino - benzoyl - glycyl - sarcosine ethyl ester, a p-amino-benzoyl-glutamic acid diethyl ester, a d -amino-g -valerolactone, an ethylamine, a glycylvaline, a glycylvalineproline or a threonine residue) by treating 2-nitro-3 - hydroxy - 4 - methylbenzoic acid with sodium to form the sodium salt, reacting this with benzyl chloride to form 2-nitro-3-benzyloxy-4-methylbenzoic acid, converting the acid into its corresponding acid chloride and reacting this with the parent molecule of the residue R to form N-(2-nitro-3-benzyloxy-4-methylbenzoyl)-R, which is then catalytically hydrogenated; d - amino - g - valerolactone by reacting d -chloro-g -valerolactone with potassium phthalimide followed by acid hydrolysis; and N-(2-amino - 3 - hydroxy - 4 - methylbenzoyl) glycine from the corresponding 2-nitro ethyl ester by hydrolysis to form N-(2-nitro-3-hydroxy-4-methylbenzoyl) glycine which is then hydrogenated.
GB30910/56A 1955-10-10 1956-10-10 Phenoxazone-dicarboxylic acid derivatives Expired GB807687A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE807687X 1955-10-10

Publications (1)

Publication Number Publication Date
GB807687A true GB807687A (en) 1959-01-21

Family

ID=6722894

Family Applications (1)

Application Number Title Priority Date Filing Date
GB30910/56A Expired GB807687A (en) 1955-10-10 1956-10-10 Phenoxazone-dicarboxylic acid derivatives

Country Status (1)

Country Link
GB (1) GB807687A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0209875A1 (en) * 1985-07-25 1987-01-28 Roche Diagnostics GmbH Resorufin derivatives and process for their preparation
WO2023201067A3 (en) * 2022-04-14 2023-11-16 W. L. Gore & Associates, Inc. No-releasing coating

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0209875A1 (en) * 1985-07-25 1987-01-28 Roche Diagnostics GmbH Resorufin derivatives and process for their preparation
US5304645A (en) * 1985-07-25 1994-04-19 Boehringer Mannheim Gmbh Resorufin derivatives
WO2023201067A3 (en) * 2022-04-14 2023-11-16 W. L. Gore & Associates, Inc. No-releasing coating

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